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## Protocol Section ### Identification Module **NCT ID:** NCT02740179 **Brief Title:** Effects of Eplerenone on Cardiovascular Disease in HIV (MIRACLE HIV Study) **Official Title:** Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV--The MIRACLE HIV Study #### Organization Study ID Info **ID:** 2016P000464 #### Organization **Class:** OTHER **Full Name:** Massachusetts General Hospital ### Status Module #### Completion Date **Date:** 2022-03-17 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-06 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-03-17 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-06-02 **Type:** ACTUAL **Results First Submit Date:** 2023-03-16 **Results First Submit QC Date:** 2023-05-04 #### Start Date **Date:** 2017-01 **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2016-04-15 **Type:** ESTIMATED **Study First Submit Date:** 2016-04-07 **Study First Submit QC Date:** 2016-04-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Investigator Affiliation:** Massachusetts General Hospital **Investigator Full Name:** Steven K. Grinspoon, MD **Investigator Title:** Professor of Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** HIV-infected individuals treated with antiretroviral medications are living longer, but have an increased risk of heart disease when compared to non-HIV-infected individuals. A hormone called aldosterone, which regulates blood pressure and sodium balance, is elevated in the HIV population in association with with increased belly fat and altered glucose metabolism. Elevations in aldosterone hormone may also be associated with abnormal blood flow, inflammation, and coronary plaque in the heart. This study is being conducted to evaluate whether therapies to reduce the actions of aldosterone may decrease the burden and progression of heart disease in the HIV population. **Detailed Description:** This is a 12 month randomized, placebo controlled study enrolling HIV-infected individuals with no known history of cardiovascular disease. Eplerenone is a mineralocorticoid receptor antagonist, which can block aldosterone activation. This medication is approved by the FDA for high blood pressure and heart failure. This study aims to investigate the effect of eplerenone on other measures of cardiovascular disease in HIV. Using PET, MRI, and CT imaging technology, this study will evaluate whether eplerenone can improve coronary flow reserve and myocardial inflammation/fibrosis, in addition to atherosclerotic plaque build-up among the HIV population. The study also includes teaching on lifestyle modification to promote a healthy diet and exercise program.There are 3 overnight visits in addition to safety visits. ### Conditions Module **Conditions:** - HIV **Keywords:** - Eplerenone - Cardiovascular Disease - Mineralocorticoid Receptor Antagonist - Coronary Vasculature - Myocardial Inflammation - Myocardial Fibrosis - Atherosclerosis - Aldosterone ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months **Intervention Names:** - Drug: Eplerenone - Behavioral: Lifestyle Modification **Label:** Eplerenone **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months **Intervention Names:** - Drug: Placebo - Behavioral: Lifestyle Modification **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Eplerenone **Description:** Eplerenone 50mg by mouth twice daily **Name:** Eplerenone **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo by mouth twice daily **Name:** Placebo **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Eplerenone - Placebo **Description:** Counseling regarding diet and healthy activity **Name:** Lifestyle Modification **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by coronary flow reserve measured via cardiac positron emission tomography. Coronary flow reserve is given by the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest. **Measure:** Myocardial Perfusion by PET **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by myocardial blood flow measured via cardiac magnetic resonance imaging **Measure:** Myocardial Perfusion by MRI **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in myocardial inflammation measured by extracellular mass index (a measure of the inflammation within the heart) via cardiac magnetic resonance imaging **Measure:** Myocardial Inflammation **Time Frame:** 12 Months #### Secondary Outcomes **Description:** Change (value at 12 months minus value at baseline) in coronary plaque measured via coronary computed tomography angiogram assessed by coronary calcium score Scale: minimum 0 to maximum no limit, higher score indicates more plaque **Measure:** Coronary Plaque **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in serum hs-cTnT **Measure:** Markers of Vascular Dysfunction **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in plasma hsIL-6 **Measure:** Markers of Systemic Inflammation hsIL-6 **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in plasma hsCRP **Measure:** Markers of Systemic Inflammation hsCRP **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in plasma MCP-1 **Measure:** Markers of Immune Activation MCP-1 **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in plasma sCD163 **Measure:** Markers of Immune Activation sCD163 **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in serum NT-proBNP **Measure:** Markers of Subclinical Injury **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in myocardial fibrosis measured by T1 (a signal intensity that measures fibrosis) via cardiac magnetic resonance imaging **Measure:** Markers of Fibrosis **Time Frame:** 12 Months **Description:** Percentage change (value at 12 months minus value at baseline) in target to background ratio (a measure of arterial inflammation) of the index vessel measured via positron emission tomography/computed tomography **Measure:** Arterial Inflammation **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in plasma LpPLA2 **Measure:** Markers of Arterial Inflammation **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in left ventricular mass on cardiac magnetic resonance imaging **Measure:** Assessment of Cardiac Structure by Left Ventricular Mass on Cardiac Imaging **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in global circumferential strain (GCS) on cardiac magnetic resonance imaging **Measure:** Assessment of Cardiac Systolic Function Via Cardiac Imaging **Time Frame:** 12 Months **Description:** Change (value at 12 months minus value at baseline) in left ventricular end diastolic volume on cardiac magnetic resonance imaging **Measure:** Assessment of Cardiac Diastolic Function Via Cardiac Imaging **Time Frame:** 12 Months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Ages 40-65 years 2. Antiretroviral use (ART) \>12 months and HIV viral load \<100 copies/mL 3. VAT\> 110cm2 Exclusion Criteria: 1. Antihypertensive use including, ACE Inhibitor, ARB, MR blockade, diuretic, potassium (K) supplementation; or BP\>140/90 mmHg. Stable use (\>3 months) of beta-blockers or calcium channel blockers (CCB) (except verapamil) is allowed. 2. Unstable statin use \<12 months. Stable use (\>12 months) is allowed. 3. Use of full dose ritonavir, nelfinavir, clarithromycin, and other strong inhibitors of CYP3A4, as well as CYP3A4 inducers. 4. Continuous oral steroid use (equivalent to prednisone \> 5 mg daily) within the last 3 months. 5. Uncontrolled diabetes requiring insulin and/or HbA1c \> 7.5%. 6. Creatinine (Cr) \> 1.5 mg/dL or estimated GFR\<60 mL/min/1.73m2. 7. K \> 5.5 mEq/L. 8. Hemoglobin \< 10 g/dL. 9. Known liver disease or ALT \>3x ULN. 10. History of congestive heart failure, stroke, myocardial infarction, or known coronary artery disease. 11. Pregnant, actively seeking pregnancy or breastfeeding. 12. Estrogen, progestin derivative, or other sex steroid use within last 3 months. Stable physiologic testosterone replacement (\> 3 months) is acceptable. 13. Current bacterial or other infections. 14. Active substance abuse. 15. Significant radiation exposure over the course of the year prior to randomization (e.g., radiation therapy, PCI, catheter ablation of arrhythmia) within 12 months of randomization. 16. Previous reaction or contraindication to iodine-containing contrast media and gadolinium. 17. Coronary artery luminal narrowing \>70% on coronary CTA. **Maximum Age:** 65 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Zip:** 02114 ### References Module #### References **Citation:** Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, Lo J, Adler GK, Grinspoon SK. RAAS Activation Is Associated With Visceral Adiposity and Insulin Resistance Among HIV-infected Patients. J Clin Endocrinol Metab. 2015 Aug;100(8):2873-82. doi: 10.1210/jc.2015-1461. Epub 2015 Jun 18. **PMID:** 26086328 ## Document Section ### Large Document Module #### Large Docs - Date: 2022-11-08 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 419403 - Type Abbrev: Prot_SAP - Upload Date: 2023-03-09T13:37 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M8485 - Name: Fibrosis - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown - ID: M26188 - Name: Atherosclerosis - Relevance: LOW - As Found: Unknown - ID: M12157 - Name: Myocarditis - Relevance: LOW - As Found: Unknown - ID: T4005 - Name: Myocarditis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002318 - Term: Cardiovascular Diseases ### Intervention Browse Module - Ancestors - ID: D000000451 - Term: Mineralocorticoid Receptor Antagonists - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000062865 - Term: Diuretics, Potassium Sparing - ID: D000004232 - Term: Diuretics - ID: D000045283 - Term: Natriuretic Agents - ID: D000000959 - Term: Antihypertensive Agents ### Intervention Browse Module - Browse Branches - Abbrev: AnAg - Name: Antihypertensive Agents - Abbrev: NaAg - Name: Natriuretic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1823 - Name: Eplerenone - Relevance: HIGH - As Found: Everyday - ID: M3797 - Name: Mineralocorticoid Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M11871 - Name: Mineralocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M7411 - Name: Diuretics - Relevance: LOW - As Found: Unknown - ID: M30025 - Name: Diuretics, Potassium Sparing - Relevance: LOW - As Found: Unknown - ID: M4277 - Name: Antihypertensive Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077545 - Term: Eplerenone ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Eplerenone **Deaths Num Affected:** 1 **Deaths Num At Risk:** 20 **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** EG000 **Other Num Affected:** 12 **Other Num at Risk:** 20 **Serious Number Affected:** 1 **Serious Number At Risk:** 20 **Title:** Eplerenone **Group ID:** EG001 **Title:** Placebo **Deaths Num At Risk:** 20 **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** EG001 **Other Num Affected:** 11 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Placebo **Frequency Threshold:** 5 #### Other Events **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Gastrointestinal Symptoms **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Upper Respiratory Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Other Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Musculoskeletal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Cardiovascular Symptoms **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Injuries **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Other Respiratory Symptoms **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Urinary Volume Increase **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Underwent Non-Cardiac Elective Procedure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** #### Serious Events **Term:** Medical condition leading to death **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Unrelated to study medication **Organ System:** Social circumstances ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Group ID:** EG001 **Num At Risk:** 20 **Time Frame:** 12 Months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 20 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 40 **Units:** Participants ### Group **ID:** BG000 **Title:** Eplerenone **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity ### Group **ID:** BG001 **Title:** Placebo **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 7 **Value:** 53 #### Measurement **Group ID:** BG001 **Spread:** 6 **Value:** 56 #### Measurement **Group ID:** BG002 **Spread:** 7 **Value:** 55 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 10 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 30 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 7 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 33 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 22 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 40 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** sgrinspoon@mgh.harvard.edu **Organization:** Massachusetts General Hospital **Phone:** 617-724-9109 **Title:** Dr. Steven K. Grinspoon ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.72 **P-Value Comment:** P value for Change in Coronary Flow Reserve on Cardiac PET **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.03 **P-Value Comment:** P value for Change in Stress Myocardial Blood Flow on Cardiac MRI **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.38 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.09 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.03 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** Analyses performed on log transformation of data **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.09 **P-Value Comment:** P value for Change in Plasma IL-6 **Parameter Type:** **Parameter Value:** **Statistical Comment:** Analyses performed after log transformation of data **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.36 **P-Value Comment:** P value for Change in Plasma hsCRP **Parameter Type:** **Parameter Value:** **Statistical Comment:** Analyses performed after log transformation of data **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.88 **P-Value Comment:** P value for Change in Plasma MCP-1 **Parameter Type:** **Parameter Value:** **Statistical Comment:** Analyses performed after log transformation of data **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.17 **P-Value Comment:** P value for Change in Plasma sCD163 **Parameter Type:** **Parameter Value:** **Statistical Comment:** Analyses performed after log transformation of data **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 10 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.28 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** Analyses performed after log transformation of data **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 11 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.32 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 12 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.003 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 13 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.73 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 14 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.56 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 15 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.03 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Kruskal-Wallis **Tested Non-Inferiority:** ### Outcome Measure 16 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.03 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.64 - **Upper Limit:** - **Value:** 0.01 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.48 - **Upper Limit:** - **Value:** -0.07 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.56 - **Upper Limit:** - **Value:** 0.09 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.68 - **Upper Limit:** - **Value:** -0.53 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.3 - **Spread:** - **Upper Limit:** 4.3 - **Value:** 0.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -2.2 - **Spread:** - **Upper Limit:** -0.1 - **Value:** -0.7 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 6 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 41 - **Value:** 5 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.13 - **Spread:** - **Upper Limit:** 0.00 - **Value:** 0.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.00 - **Spread:** - **Upper Limit:** 0.74 - **Value:** 0.00 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.8 - **Spread:** - **Upper Limit:** 0.4 - **Value:** -0.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.5 - **Spread:** - **Upper Limit:** 2.2 - **Value:** 0.2 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3841 - **Spread:** - **Upper Limit:** 718 - **Value:** 189 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -261 - **Spread:** - **Upper Limit:** 2346 - **Value:** 591 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 49 - **Spread:** - **Upper Limit:** 365 - **Value:** 285 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 241 - **Spread:** - **Upper Limit:** 352 - **Value:** 292 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -384 - **Spread:** - **Upper Limit:** -11 - **Value:** -275 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -304 - **Spread:** - **Upper Limit:** 100 - **Value:** -160 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.6 - **Spread:** - **Upper Limit:** 41.0 - **Value:** 19.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -25.6 - **Spread:** - **Upper Limit:** 63.5 - **Value:** 2.8 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 74 - **Value:** 25 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -50 - **Spread:** - **Upper Limit:** 85 - **Value:** 1 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -21.9 - **Spread:** - **Upper Limit:** -2.6 - **Value:** -12.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -1.6 - **Spread:** - **Upper Limit:** 11.0 - **Value:** 5.1 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -6.6 - **Spread:** - **Upper Limit:** 25.0 - **Value:** 3.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -10.1 - **Spread:** - **Upper Limit:** 9.5 - **Value:** 2.6 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -25 - **Spread:** - **Upper Limit:** 26 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -3 - **Spread:** - **Upper Limit:** 17 - **Value:** 9 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.9 - **Spread:** - **Upper Limit:** 1.0 - **Value:** -1.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.4 - **Spread:** - **Upper Limit:** 4.1 - **Value:** 2.3 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 28 - **Upper Limit:** - **Value:** -13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 26 - **Upper Limit:** - **Value:** 10 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by coronary flow reserve measured via cardiac positron emission tomography. Coronary flow reserve is given by the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Myocardial Perfusion by PET **Type:** PRIMARY **Unit of Measure:** unitless ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** Change (value at 12 months minus value at baseline) in myocardial perfusion assessed by myocardial blood flow measured via cardiac magnetic resonance imaging **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Myocardial Perfusion by MRI **Type:** PRIMARY **Unit of Measure:** mL/min/g ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** Change (value at 12 months minus value at baseline) in myocardial inflammation measured by extracellular mass index (a measure of the inflammation within the heart) via cardiac magnetic resonance imaging **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Myocardial Inflammation **Type:** PRIMARY **Unit of Measure:** g/m^2 ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Description:** Change (value at 12 months minus value at baseline) in coronary plaque measured via coronary computed tomography angiogram assessed by coronary calcium score Scale: minimum 0 to maximum no limit, higher score indicates more plaque **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Coronary Plaque **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Description:** Change (value at 12 months minus value at baseline) in serum hs-cTnT **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Vascular Dysfunction **Type:** SECONDARY **Unit of Measure:** ng/L ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Description:** Change (value at 12 months minus value at baseline) in plasma hsIL-6 **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Systemic Inflammation hsIL-6 **Type:** SECONDARY **Unit of Measure:** pg/mL ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Description:** Change (value at 12 months minus value at baseline) in plasma hsCRP **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Systemic Inflammation hsCRP **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 8 **Description:** Change (value at 12 months minus value at baseline) in plasma MCP-1 **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Immune Activation MCP-1 **Type:** SECONDARY **Unit of Measure:** pg/mL ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 9 **Description:** Change (value at 12 months minus value at baseline) in plasma sCD163 **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Immune Activation sCD163 **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 10 **Description:** Change (value at 12 months minus value at baseline) in serum NT-proBNP **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Subclinical Injury **Type:** SECONDARY **Unit of Measure:** ng/L ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 11 **Description:** Change (value at 12 months minus value at baseline) in myocardial fibrosis measured by T1 (a signal intensity that measures fibrosis) via cardiac magnetic resonance imaging **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Fibrosis **Type:** SECONDARY **Unit of Measure:** ms ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 12 **Description:** Percentage change (value at 12 months minus value at baseline) in target to background ratio (a measure of arterial inflammation) of the index vessel measured via positron emission tomography/computed tomography **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available as part of a substudy. **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Arterial Inflammation **Type:** SECONDARY **Unit of Measure:** percentage change ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 13 **Description:** Change (value at 12 months minus value at baseline) in plasma LpPLA2 **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available as part of a substudy. **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Markers of Arterial Inflammation **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 14 **Description:** Change (value at 12 months minus value at baseline) in left ventricular mass on cardiac magnetic resonance imaging **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Assessment of Cardiac Structure by Left Ventricular Mass on Cardiac Imaging **Type:** SECONDARY **Unit of Measure:** g ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 15 **Description:** Change (value at 12 months minus value at baseline) in global circumferential strain (GCS) on cardiac magnetic resonance imaging **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Analyses performed on data available **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Assessment of Cardiac Systolic Function Via Cardiac Imaging **Type:** SECONDARY **Unit of Measure:** percentage GCS ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo #### Outcome Measure 16 **Description:** Change (value at 12 months minus value at baseline) in left ventricular end diastolic volume on cardiac magnetic resonance imaging **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 12 Months **Title:** Assessment of Cardiac Diastolic Function Via Cardiac Imaging **Type:** SECONDARY **Unit of Measure:** mL ##### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG000 **Title:** Eplerenone ##### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Eplerenone 50 mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Eplerenone: Eplerenone 50mg by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** FG000 **Title:** Eplerenone #### Group **Description:** Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 12 months Placebo: Placebo by mouth twice daily Lifestyle Modification: Counseling regarding diet and healthy activity **ID:** FG001 **Title:** Placebo #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 19 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05468879 **Brief Title:** Bioequivalence Study of 3 mg Glimepiride Tablet in Indonesia Healthy Subjects **Official Title:** Bioequivalence Study of 3 mg Glimepiride Tablet in Indonesia Healthy Subjects #### Organization Study ID Info **ID:** 540/STD/PML/2020 #### Organization **Class:** INDUSTRY **Full Name:** PT Harsen Laboratories ### Status Module #### Completion Date **Date:** 2021-01-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-10-23 **Type:** ACTUAL #### Start Date **Date:** 2020-09-21 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2022-07-21 **Type:** ACTUAL **Study First Submit Date:** 2022-07-19 **Study First Submit QC Date:** 2022-07-20 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** PT Pharma Metric Labs #### Lead Sponsor **Class:** INDUSTRY **Name:** PT Harsen Laboratories #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The study was conducted toinvestigate whether the bioavailability of 3 mg Glimepiride Tablet Manufactured by PT. Harsen Laboratories was bioequivalent to the reference product, 3 mg Amaryl® Tablet Manufactured by PT. Aventis Indonesia Pharma, Indonesia. **Detailed Description:** The study was conducted following an oral administration of one tablet of the test drug (3 mg Glimepiride Tablet) or one tablet of the reference drug (3 mg Amaryl® Tablet ). Blood samples were drawn before dosing (0 h) and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, and 30 hours after drug administration. The entire subjects were given 60 mL of 20% glucose solution to minimize hypoglycemic effects at 15, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75 and 4 hours after drug administration. Following a washout period of one week, this procedure was repeated using the alternate drug. The plasma concentrations of glimepiride were determined by means of LC-MS/MS system. The LLOQ is 1.99 ng/mL of glimepiride. The pharmacokinetic parameters used in this study were area under the concentration-time curve of glimepiride from time zero to 30 hours (AUCt), area under the concentration-time curve from time zero to infinite (AUCinf), maximum concentration (Cmax), time required to reach the maximum concentration (tmax) and the elimination half life (t½). ### Conditions Module **Conditions:** - Drug Use **Keywords:** - Bioequivalence study - Glimepiride - Indonesia - cross-over design study - pharmacokinetics ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Randomized, single blind, two-period, single dose, cross-over study with one week washout period under fasted condition ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 34 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants received Glimepiride 3 mg Tablet with 240 mL of 20% glucose solution **Intervention Names:** - Drug: Glimepiride **Label:** Glimepiride 3 mg Tablet **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants received Amaryl® 3 mg tablet (Glimepiride 3 mg) with 240 mL of 20% glucose solution **Intervention Names:** - Drug: Amaryl® **Label:** Amaryl® 3 mg tablet **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Glimepiride 3 mg Tablet **Description:** Glimepiride is a sulfonylurea, indicated as an adjunct to proper dietary management, exercise and weight reduction to lower the blood glucose in patients with type 2 diabetes whose hyperglycemia cannot be controlled by diet and exercise alone. **Name:** Glimepiride **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Amaryl® 3 mg tablet **Description:** Amaryl® **Name:** Amaryl® **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** 90% Confidence Interval **Measure:** Maximum plasma concentration (Cmax) **Time Frame:** before dosing (0 hour) and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, and 30 hours after drug administration **Description:** 90% Confidence Interval **Measure:** Area Under Curve from 0 to 30 hours (AUCt) **Time Frame:** before dosing (0 hour) and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, and 30 hours after drug administration #### Secondary Outcomes **Description:** Pharmacokinetics Parameter **Measure:** Maximum plasma concentration (Cmax) **Time Frame:** before dosing (0 hour) and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, and 30 hours after drug administration **Description:** Pharmacokinetics Parameter **Measure:** Area Under Curve from 0 to 30 hours (AUCt) **Time Frame:** before dosing (0 hour) and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, and 30 hours after drug administration ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * healthy male and female * had read the subject information and signed informed consent documents * were age between 18 to 55 years * had body mass index between 18 to 25 kg/m2 * had a normal electrocardiogram * had normal blood pressure (systolic was ranged between 90 to 120 mmHg and diastolic was ranged between 60 to 80 mmHg) * had normal heart rate (ranged between 60 to 100 bpm) * have no significant disease in medical history; have no significant abnormal values in laboratory and physical examination during screening * had acceptance to use protection (condom) during intercourse with their spouse throughout the study Exclusion Criteria: * Pregnant and/or nursing woman. * Those with a history of contraindication or hypersensitivity to glimepiride, other antidiabetic agent or other ingredients in the study products or a history of serious allergic reaction to any drug, significant allergic disease or allergic reaction. * Those with a history or presence of medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease. * Those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities. * Those who using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetic of the study drug, within one week prior to the drug administration day. * Those who had participated in any clinical study within 3 months prior to the study (\< 90 days). * Those who donated or lost 300 mL (or more) of blood within 3 months prior to the study. * Those who smoked more than 10 cigarettes a day * Those with a history of travelling to another city within the last 14 days * Those with a history of direct contact with a COVID-19 positive person in the subject's neighborhood * Those with a history or present of sore throat, fever (with temperature more than 37°C) or dyspnea within the last 14 days * Those who reactive to anti SARS CoV-2 test * Those who were positive to HIV, HBsAg, and HCV tests (to be kept confidential). * Those with a history of drug or alcohol abused within 12 months prior to screening for this study * Those who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Jakarta **Country:** Indonesia **Facility:** PT Pharma Metric Labs **State:** DKI Jakarta **Zip:** 10520 ### References Module #### References **Citation:** Liu Y, Zhang MQ, Zhu JM, Jia JY, Liu YM, Liu GY, Li S, Weng LP, Yu C. Bioequivalence and pharmacokinetic evaluation of two formulations of glimepiride 2 mg: a single-dose, randomized-sequence, open-label, two-way crossover study in healthy Chinese male volunteers. Clin Ther. 2010 May;32(5):986-95. doi: 10.1016/j.clinthera.2010.04.016. **PMID:** 20685507 **Citation:** Jung SH, Chae JW, Song BJ, Kwona KI. Bioequivalence Comparison of Two Formulations of Fixed-Dose Combination Glimepiride/Metformin (2/500 mg)Tablets in Healthy Volunteers. Iran J Pharm Res. 2014 Spring;13(2):365-71. **PMID:** 25237332 **Citation:** Zhu J, Li Y, Xiang Y, Zhou L, Li Y. Magnetic solid phase extraction followed with LC-MS/MS for determination of glimepiride in beagle dog plasma and its application to bioequivalence study. J Pharm Biomed Anal. 2020 May 30;184:113180. doi: 10.1016/j.jpba.2020.113180. Epub 2020 Feb 15. **PMID:** 32092631 **Citation:** Jovanovic D, Stojsic D, Zlatkovic M, Jovic-Stosic J, Jovanovic M. Bioequivalence assessment of the two brands of glimepiride tablets. Vojnosanit Pregl. 2006 Dec;63(12):1015-20. doi: 10.2298/vsp0612015j. **PMID:** 17252706 #### See Also Links **Label:** Amaryl® (Glimepiride) Tablet 1,2, and 4 mg, Product Monograph **URL:** https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020496s021lbl.pdf ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2022-08-05 - Date Unknown: Unknown #### Event: RESET - Date: 2023-07-06 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: Rare - Name: Rare Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000000889 - Term: Anti-Arrhythmia Agents - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M252104 - Name: Glimepiride - Relevance: HIGH - As Found: Correlative - ID: M4213 - Name: Anti-Arrhythmia Agents - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000057619 - Term: Glimepiride ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2022-08-05 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2022-08-05 - Reset Date: 2023-07-06 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05474079 **Acronym:** EXSTATIC **Brief Title:** Exercise Training & Statins for Cardiovascular Health **Official Title:** The Effects of Supervised Exercise Training in the Primary Prevention of Cardiovascular Disease in Stain-Users and Non Statin-Users #### Organization Study ID Info **ID:** STA- 5035 #### Organization **Class:** OTHER **Full Name:** Cardiff Metropolitan University ### Status Module #### Completion Date **Date:** 2026-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-07 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-06 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-07-20 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2022-07-26 **Type:** ACTUAL **Study First Submit Date:** 2022-03-01 **Study First Submit QC Date:** 2022-07-21 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Health and Care Research Wales #### Lead Sponsor **Class:** OTHER **Name:** Cardiff Metropolitan University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Cardiovascular disease (CVD) refers to any condition that affects the heart and/or blood vessels (e.g. heart attack, stroke) and is the leading cause of death and disability worldwide. Regular exercise and statin therapy are widely recommended as frontline prevention strategies to reduce CVD risk. Recent changes to National Health Service (NHS) healthcare guidelines state that even individuals with a relatively low risk of CVD (≥10% risk score) should take a statin. When prescribed after a heart attack or stroke, both exercise and statins reduce the risk of a CVD-related death by \~25%, with some evidence to suggest that the combination of these therapies may offer additive cardiovascular protection. However, far less is known about the combined effects of exercise and statin therapy in primary CVD prevention (i.e. before a CVD event). Poor blood vessel function represents the earliest stage of CVD, which can be measured with ultrasound at different regions of the body (limbs, brain, heart) to sensitively detect early CVD risk. Regular exercise provides a variety of cardiovascular benefits and has a direct therapeutic effect on blood vessel function. In contrast, statin therapy primarily reduces CVD risk by lowering cholesterol, which may also improve blood vessel function. Although both therapies can separately reduce CVD risk, the interaction between exercise training and statin therapy on blood vessel function has never been directly compared in the setting of primary prevention, and it's currently unknown whether a combination of both therapies offers additional cardiovascular benefit. Therefore, the main aims of this study are to (i) investigate the effect of supervised exercise training on blood vessel function (limbs, brain, heart) in individuals with a CVD-risk score of ≥10% and (ii) examine whether these exercise effects differ in individuals taking a statin compared to those not taking a statin. **Detailed Description:** Over 340,000 people in Wales live with cardiovascular disease (CVD). It causes 28% of all annual deaths and costs the Welsh NHS £469 million per year (British Heart Foundation, 2019). Physical inactivity causes a third of all CVD cases and only 53% of Welsh adults currently meet the recommended minimum physical activity guidelines (Statistics for Wales, 2019). Accordingly, Wales is the most physically inactive nation in the UK with one of the highest rates of CVD. Regular exercise is widely recommended by GPs as a frontline prevention strategy to reduce CVD-risk. Similarly, statins are also routinely prescribed as part of primary healthcare across the UK to lower cholesterol levels and reduce CVD-risk. Recent changes to NHS primary healthcare guidelines state that even individuals with a relatively low risk of CVD (10-year CVD-risk score ≥10%; QRISK3) should take a statin. When prescribed after a heart attack or stroke, both exercise and statins reduce the risk of a CVD-related death by \~25%; some evidence suggests that the combination of these therapies may offer additive cardiovascular protection. However, far less is known about the combined effects of exercise and statin therapy in primary CVD prevention. Sensitive ultrasound techniques can be used to examine vascular, cerebrovascular and cardiac structure and function to provide a comprehensive overview of cardiovascular health. Poor vascular function represents the earliest stage of CVD and is more sensitive at detecting CVD risk than traditional risk factors. Regular exercise provides a variety of cardiovascular benefits and has a direct therapeutic effect on vascular function. In contrast, statin therapy primarily reduces CVD-risk by lowering cholesterol, which may also improve vascular function. Although both therapies can separately reduce CVD risk, the interaction between exercise training and statin therapy on vascular function has never been directly compared in the setting of primary prevention; and it is currently unknown whether a combination of both therapies offers additional cardiovascular benefit. This study will utilise a comprehensive series of cutting-edge vascular, cerebrovascular and cardiac ultrasound techniques to examine the effectiveness of exercise and statin therapy as primary CVD prevention strategies. If results demonstrate that exercise training provides similar cardiovascular benefits to statin therapy, and/or the combination of these preventive strategies offer additive benefit, this could have considerable implications on primary prevention healthcare recommendations. ### Conditions Module **Conditions:** - Risk Reduction - Cardiovascular Diseases ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 80 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The exercise training program will consist of individually tailored, progressive moderate-intensity aerobic exercise. Exercise training will comprise of a combination of treadmill, cross-trainer and cycle ergometer-based exercise. Exercise will progressively increase in both intensity and duration throughout the course of the intervention. Participants will begin the intervention with 30 minutes of moderate-intensity aerobic exercise at 40% heart rate reserve (HRR) three times per week for the initial 4 weeks. From week 4, exercise intensity will increase to 50% HRR, and at week 6 the duration of each session will increase to 45 minutes. From week 8, participants will exercise at an intensity of 60% HRR for 45 minutes, and from week 10, this will increase to five sessions per week. **Intervention Names:** - Other: Moderate intensity exercise training **Label:** Statin users exercise intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants randomized to the conventional primary care control group will not receive any supervision or guidance throughout the 12-week intervention beyond the initial standard healthcare advice provided by their general practitioner (GP). **Label:** Statin users conventional care control **Type:** NO_INTERVENTION #### Arm Group 3 **Description:** The exercise training program will consist of individually tailored, progressive moderate-intensity aerobic exercise. Exercise training will comprise of a combination of treadmill, cross-trainer and cycle ergometer-based exercise. Exercise will progressively increase in both intensity and duration throughout the course of the intervention. Participants will begin the intervention with 30 minutes of moderate-intensity aerobic exercise at 40% HRR three times per week for the initial 4 weeks. From week 4, exercise intensity will increase to 50% HRR, and at week 6 the duration of each session will increase to 45 minutes. From week 8, participants will exercise at an intensity of 60% HRR for 45 minutes, and from week 10, this will increase to five sessions per week. **Intervention Names:** - Other: Moderate intensity exercise training **Label:** Non-statin users exercise intervention **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Participants randomized to the conventional primary care control group will not receive any supervision or guidance throughout the 12-week intervention beyond the initial standard healthcare advice provided by their GP. **Label:** Non-statin users conventional care control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Non-statin users exercise intervention - Statin users exercise intervention **Description:** The exercise training program will consist of individually tailored, progressive moderate-intensity aerobic exercise. Exercise training will comprise of a combination of treadmill, cross-trainer and cycle ergometer-based exercise. Exercise will progressively increase in both intensity and duration throughout the course of the intervention. Participants will begin the intervention with 30 minutes of moderate-intensity aerobic exercise at 40% HRR three times per week for the initial 4 weeks. From week 4, exercise intensity will increase to 50% HRR, and at week 6 the duration of each session will increase to 45 minutes. From week 8, participants will exercise at an intensity of 60% HRR for 45 minutes, and from week 10, this will increase to five sessions per week. **Name:** Moderate intensity exercise training **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Each participant will be issued with a small lightweight tri-axial accelerometer (activPAL Professional Physical Activity Monitor Technologies Ltd., Glasgow, UK), that will examine 7-day habitual physical activity levels. This device will be worn around the participant's waist continuously for seven consecutive days and will assess and monitor any physical activity and categorise activity bouts into light, moderate and vigorous intensity activity based on metabolic equivalent of task (METS)/hour/day. **Measure:** Change in 7-day physical activity monitoring: Intensity of activity **Time Frame:** Pre and post intervention (12 weeks) **Description:** Each participant will be issued with a small lightweight tri-axial accelerometer (activPAL Professional Physical Activity Monitor Technologies Ltd., Glasgow, UK), that will examine 7-day habitual physical activity levels. This device will be worn around the participant's waist continuously for seven consecutive days and will assess the frequency of any activity bout (bouts/hour/day). **Measure:** Change in 7-day physical activity monitoring: Frequency of activity **Time Frame:** Pre and post intervention (12 weeks) **Description:** Each participant will be issued with a small lightweight tri-axial accelerometer (activPAL Professional Physical Activity Monitor Technologies Ltd., Glasgow, UK), that will examine 7-day habitual physical activity levels. This device will be worn around the participant's waist continuously for seven consecutive days and will assess the duration of any activity bout (mins per bout). **Measure:** Change in 7-day physical activity monitoring: Duration of activity **Time Frame:** Pre and post intervention (12 weeks) **Description:** Each participant will be issued with a small lightweight tri-axial accelerometer (activPAL Professional Physical Activity Monitor Technologies Ltd., Glasgow, UK), that will examine 7-day habitual physical activity levels. This device will be worn around the participant's waist continuously for seven consecutive days and will assess and monitor the frequency of any sedentary periods (bouts/hour/day) **Measure:** Change in 7-day physical activity monitoring: Frequency of sedentary periods **Time Frame:** Pre and post intervention (12 weeks) **Description:** Each participant will be issued with a small lightweight tri-axial accelerometer (activPAL Professional Physical Activity Monitor Technologies Ltd., Glasgow, UK), that will examine 7-day habitual physical activity levels. This device will be worn around the participant's waist continuously for seven consecutive days and will assess and monitor the duration of any sedentary periods (mins per bout) **Measure:** Change in 7-day physical activity monitoring: Duration of sedentary periods **Time Frame:** Pre and post intervention (12 weeks) **Description:** participant will be issued with a wearable automated blood pressure monitoring device. This validated Mobil-O-Graph system (IEM Germany) will non-invasively measure 24-hour ambulatory blood pressure, aortic pressure and vascular haemodynamics. A small blood pressure cuff will be placed around the upper arm of the participant and connected to a halter monitor for 24 hours. Clear instructions on how to fit and position this device, as well as guidance on how long this device should be worn will be provided by a member of the research team **Measure:** Change in 24-hour ambulatory blood pressure **Time Frame:** Pre and post intervention (12 weeks) **Description:** Participants will be required to complete a maximal exercise test (maximal oxygen consumption \[VO2max\] test) on a motorised treadmill . Initially, participants will be required to complete a 2 minute slow walking warm-up. The test will then progressively increase in speed and gradient every 2 minutes until the participant is no longer able to continue the exercise (volitional exhaustion). Throughout this procedure each participant will be required to wear a face mask connected to a gas analyser, allowing breath-by-breath oxygen consumption to be continuously measured Upon completion of the test, the gradient and the speed of the treadmill will be reduced and the participants will perform a cool down for 3-5 minutes. **Measure:** Change in VO2peak cardiopulmonary max test **Time Frame:** Pre and post intervention (12 weeks) #### Primary Outcomes **Description:** Brachial artery FMD, as a non-invasive measure of endothelial nitric oxide function, will be assessed using high resolution Duplex vascular ultrasonography in accordance with published guidelines. **Measure:** Change in Flow Mediated Dilatation (FMD) **Time Frame:** Pre and post intervention (12 weeks) #### Secondary Outcomes **Description:** Sublingual Glyceryl Trinitrate (GTN): Following 10 minutes of supine rest, endothelium independent vasodilator function will be assessed simultaneously in the brachial and carotid artery. A 1-minute baseline recording of the brachial and carotid artery will be acquired on the same high-resolution ultrasound device before sublingual administration of glyceryl trinitrate (GTN; 400µg). GTN is a nitric oxide donor that will cause the arteries to vasodilate allowing a short-lived increase in blood flow. Both the brachial and carotid artery will be imaged for 10-minutes following the administration of GTN and peak diameter and blood flow will be recorded. GTN has been used for many decades in clinical and research work in this and other populations. **Measure:** Change in sublingual glyceryl trinitrate (GTN) induced dilatation **Time Frame:** Pre and post intervention (12 weeks) **Description:** Cold Pressor Test: Following 15 minutes supine rest, carotid artery reactivity (CAR) to a sympathetic stimulation produced by the cold pressor test (CPT) will be measured. The same ultrasound probe will be repositioned onto the participant's neck and an image of the carotid artery will be recorded continuously for one minute before and then during 3 minutes of hand-to-wrist submersion in ice cold water (4 °C). After the 3 minute CPT, the participant will then remove their hand from the cold water and we will continue to image the carotid artery for an additional 3 minutes. Peak carotid artery diameter and blood flow velocity, and the time taken to reach these peaks during the CPT will be recorded. This procedure has been shown to be reliable and well tolerated in this population. **Measure:** Change in cold pressor induced dilatation **Time Frame:** Pre and post intervention (12 weeks) **Description:** Carotid - femoral pulse wave velocity (CF-PWV) will be recorded following 15 minutes of supine rest via applanation tonometry. This measure is the accepted gold standard for non-invasive measurement of arterial stiffness and has been previously validated in this population. The arterial wave form will be recorded at the wrist, neck and groin using a high fidelity micromanometer tipped probe and gated to a 3-lead ECG for measurement of PWV via the SphygmoCor system (SphygmoCor, AtCor-Medical, Sydney, Australia). Pulse wave analysis (PWA) will also be used to measure aortic pressure using the SphygmoCor system. **Measure:** Change in arterial stiffness **Time Frame:** Pre and post intervention (12 weeks) **Description:** Participants will then return to the assessment bed and lay supine for 10 minutes. Following this, participants will perform a carbon dioxide breathing challenge. The protocol will involve the participants breathing a fixed gas mixture of otherwise normal atmospheric air that has a mildly elevated fractional concentration of carbon dioxide (6%). This technique has been routinely used within this population and published guidelines will be followed. Normal atmospheric oxygen content is maintained throughout. Participants will be fitted with a face mask covering their nose and mouth with a one-way valve to prevent rebreathing. An elevation in the fractional concentration of carbon dioxide will be applied for 6 minutes and cerebrovascular blood flow will be measured continuously throughout this protocol, as per published guidelines. This procedure enables the maximal dilation capacity of the cerebrovascular blood vessels to be assessed. **Measure:** Change in ultrasound assessment of cerebrovascular function- Assessment of cerebrovascular reactivity **Time Frame:** Pre and post intervention (12 weeks) **Description:** Participants will perform a cyclical squat-to-stand protocol. Participants will start in a standing position and then adopt a squat position where the back of their legs are at a \~90◦ angle. This manoeuvre will be repeated and performed at frequency of 10 seconds of squatting, followed by 10 seconds of standing. The duration of the protocol will be 5 minutes. This technique has been used routinely in older populations and is well tolerated and validated. **Measure:** Change in ultrasound assessment of cerebrovascular function -Dynamic cerebral autoregulation **Time Frame:** Pre and post intervention (12 weeks) **Description:** After 15 minutes of rest, participants will perform a 10 - 15 minute bout of moderate intensity exercise at 50% predicted heart rate reserve (HRR) on a cycle ergometer. **Measure:** Change in ultrasound assessment of cerebrovascular function - Cerebrovascular reactivity to an acute bout of exercise **Time Frame:** Pre and post intervention (12 weeks) **Description:** Localised changes in cerebrovascular blood flow will be assessed during neuronal activation. The occipital lobe will be activated using a visual stimulus of a flashing checkerboard and participant's will then perform a series of short and repetitive sensory tasks. Sensory stimulation tasks will involve a simple cyclical eye opening and closing protocol, reading a short passage from an non-emotive text book and performing a simple visualisation cognitive task. This technique is frequently used in older populations and a standardised and validated protocol will be adopted. **Measure:** Change in ultrasound assessment of cerebrovascular function - Assessment of neurovascular coupling **Time Frame:** Pre and post intervention (12 weeks) **Description:** Cognitive Function Assessment: Participants will be asked to complete the Montreal Cognitive Assessment. This paper-based assessment has been validated in this population and examines short term memory, visuospatial abilities, executive functions, attention, concentration and working memory, language and orientation to time and place. The test is scored based on a minimum score of 0 to a maximum score of 30, where a score of \>26 is regarded as 'normal cognitive function' and a score of \<26 indicative of mild cognitive impairment. **Measure:** Change in Cognitive Function Assessment **Time Frame:** Pre and post intervention (12 weeks) **Description:** A 30ml blood sample will be taken from a vein in the arm and analysed for markers of cardiovascular risk. Blood samples will be analysed using the Randox Dayton+ analyser with standard proprietary reagents for total cholesterol, high-density lipoprotein, triglyceride (all lipid measures in mmol). Low-density lipoprotein will then be calculated using according to the Friedwald formula (mmol). **Measure:** Change in blood lipid profile **Time Frame:** Pre and post intervention (12 weeks) **Description:** A 30ml blood sample will be taken from a vein in the arm and analysed for markers of cardiovascular risk. Blood samples will be analysed using the Randox Dayton+ analyser with standard proprietary reagents for glucose and insulin assayed using commercially available radioimmunoassay (both measures in mmol). Using fasting glucose and insulin concentrations, we then will calculate steady-state beta cell function and insulin resistance via the homeostasis model assessment. **Measure:** Change in blood glucose and insulin profile **Time Frame:** Pre and post intervention (12 weeks) **Description:** A 30ml blood sample will be taken from a vein in the arm and simultaneously analysed for pro-inflammatory cytokines; Interleukin-1α, Interleukin-1β, Interleukin-6, Interleukin-8, Interleukin-10 Interferon-γ and Tumour Necrosis Factor-α,(all measured in pg/ml) using high sensitivity multiplex enzyme-linked immunosorbent assays (ELISA). **Measure:** Changes in blood pro-inflammatory cytokines **Time Frame:** Pre and post intervention (12 weeks) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Statin Users: * Sedentary * Non-smokers * 50-65 years old * A 10-year CVD-risk score \> 10% (estimated via QRISK3) * Weight stable (\<5% weight change over the last 3 months) * Prescription of an 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor (statin) in stable dose for a minimum of 3 months and maximum of 3 years Non-Statin Users: * Sedentary * Non-smokers * 50-65 years old * A 10-year CVD-risk score \> 10% (estimated via QRISK3) * Weight stable (\<5% weight change over the last 3 months) Exclusion Criteria (Statin Users and Non-Statin Users): * History or signs/symptoms of established cardiovascular, metabolic, renal or musculoskeletal disease * Diagnosed with familial hyperlipidaemia and/or diabetes mellitus * Stage 2 hypertension (≥160/100 mmHg) * Any contraindications to exercise (e.g. unstable angina, severe orthopaedic conditions) and/or advised by GP not to undertake exercise * BMI \>40kg/m2 * Current smoker or within 6 months of cessation * Use of any medication other than statins (e.g., fibrates, metformin, thiazolidinediones, orlistat, anti-hypertensives) that could independently alter lipid metabolism and/or vascular function * Post-menopausal female and using hormone replacement therapy, or pre-menopausal using oral contraceptives that independently alter lipid metabolism and/or vascular function **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** cjpugh@cardiffmet.ac.uk **Name:** Chris Pugh **Phone:** 02920 205293 **Role:** CONTACT **Contact 2:** **Email:** st20191506@outlook.cardiffmet.ac.uk **Name:** Xela Dafauce Bouzo **Phone:** 07585476231 **Role:** CONTACT #### Locations **Location 1:** **City:** Cardiff **Contacts:** ***Contact 1:*** - **Email:** cjpugh@cardiffmet.ac.uk - **Name:** Chris Pugh - **Phone:** 02920 205293 - **Role:** CONTACT ***Contact 2:*** - **Email:** st20191506@outlook.cardiffmet.ac.uk - **Name:** Xela Dafauce Bouzo - **Phone:** 07585476231 - **Role:** CONTACT **Country:** United Kingdom **Facility:** Cardiff Metropolitan University **Status:** RECRUITING **Zip:** CF236XD #### Overall Officials **Official 1:** **Affiliation:** Cardiff Metropolitan University **Name:** Chris Pugh **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Meshes - ID: D000002318 - Term: Cardiovascular Diseases ### Intervention Browse Module - Browse Branches - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21155 - Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01892579 **Acronym:** TAP **Brief Title:** Reducing Agitation in People With Dementia: the Customized Activity Trial **Official Title:** Reducing Agitation in People With Dementia: the Customized Activity Trial #### Organization Study ID Info **ID:** NA_00067873 #### Organization **Class:** OTHER **Full Name:** Johns Hopkins University #### Secondary ID Infos **ID:** R01AG041781 **Link:** https://reporter.nih.gov/quickSearch/R01AG041781 **Type:** NIH ### Status Module #### Completion Date **Date:** 2017-11-23 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-23 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-08-23 **Type:** ACTUAL #### Start Date **Date:** 2013-11 **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2013-07-04 **Type:** ESTIMATED **Study First Submit Date:** 2013-06-27 **Study First Submit QC Date:** 2013-07-03 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute on Aging (NIA) #### Lead Sponsor **Class:** OTHER **Name:** Johns Hopkins University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Over 5 million Americans have Alzheimer's disease or a related dementia, a progressive and irreversible neurodegenerative condition, affecting also close to 15 million family caregivers (CG). A hallmark of the disease and one of the most significant challenges in dementia care is neuropsychiatric symptoms (NPS) of which agitation is the most disabling and frequently occurring. It is associated with increased health care costs, reduced life quality, heightened caregiver burden, disease acceleration and nursing home placement. Treatment typically involves pharmacologic agents; however, these are at best modestly effective, carry serious risks including mortality, and may not reduce family distress. Recently issued position statements from medical organizations suggest nonpharmacologic strategies as first-line treatment. Nevertheless, nonpharmacological strategies for agitation remain understudied. We propose a Phase III efficacy trial to test a novel 8-session patient-centric intervention, the Tailored Activity Program. We will test the program using a randomized two-group parallel design of 250 people with dementia (PwD) and their CGs (dyads) who will be randomly assigned to received a program of tailored activities or a control intervention of equivalent in-home attention and social contact. The trial assesses PwDs' preserved capabilities, deficits, previous roles, habits, interests and home environment from which activities are developed to match PwD profiles. Families are trained to implement activities and modify them for future decline. Our primary study aim evaluates the effect of tailored activities at 3 months on agitation (Hypothesis: PwD in the tailored activity program will have less frequent agitation compared to the control intervention condition. Three secondary aims evaluate: 1) 6-month effects of tailored activities on agitation and quality of life in PwD (Hypothesis: PwD receiving tailored activities will manifest lower severity scores at 6 months and better quality of life compared to PwD in the control intervention); 2) Immediate effects of tailored activities at 3 and 6 months on CG wellbeing, and time spent providing care (Hypothesis: CGs receiving training in tailoring activities will report enhanced wellbeing and less time caregiving compared to the control intervention (3 and 6 months); and 3) Cost effectiveness of the Tailored Activity Program expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions (3 and 6 months; Hypothesis: Tailoring activities will be cost effective compared to the control intervention at each test occasion). Exploratory aims will evaluate treatment effects on psychotropic medication use and other troublesome behaviors, if effects differ by cognitive status, if CGs receiving the tailored activity program will use activities at 6 months and with what frequency, how time gained is spent, and if frequency/duration of treatment and activity use affects outcomes. If proven efficacious and cost effective, the Tailored Activity Program has potential to transform clinical practice by offering a proven nonpharmacologic treatment for agitation of PwDs at home. This trial addresses a critical clinical need and public health priority identified by recent legislative activity. **Detailed Description:** Over 5 million Americans have Alzheimer's disease or a related dementia, a progressive and irreversible neurodegenerative condition, affecting also close to 15 million family caregivers (CG). A hallmark of the disease and one of the most significant challenges in dementia care is neuropsychiatric symptoms (NPS) of which agitation is the most disabling and frequently occurring. It is associated with increased health care costs, reduced life quality, heightened caregiver burden, disease acceleration and nursing home placement. Treatment typically involves pharmacologic agents; however, these are at best modestly effective, carry serious risks including mortality, and may not reduce family distress. Recently issued position statements from medical organizations suggest nonpharmacologic strategies as first-line treatment. Nevertheless, nonpharmacological strategies for agitation remain understudied. We propose a Phase III efficacy trial to test a novel 8-session patient-centric intervention, the Customized Activity Program (CAP). We will test CAP using a randomized two-group parallel design of 250 people with dementia (PwD) and their CGs (dyads) who will be randomly assigned to CAP or a control intervention of equivalent in-home attention and social contact. CAP assesses PwDs' preserved capabilities, deficits, previous roles, habits, interests and home environment from which activities are developed to match PwD profiles. Families are trained to implement activities and modify them for future decline. A pilot phase with 60 dyads showed clinically meaningful and statistically significant reductions in agitation, with no adverse effects. Our primary study aim evaluates the effect of CAP at 3 months on agitation (Hypothesis: PwD in TAP will have lower caregiver rated agitation compared to the control intervention condition. Three secondary aims evaluate: 1) 6-month effects of TAP on agitation and quality of life in PwD (Hypothesis: PwD in CAP will manifest lower caregiver rated subscale frequency and severity scores at 6 months and better quality of life compared to PwD in the control intervention); 2) Immediate effects of CAP at 3 and 6 months on CG wellbeing, and time spent providing care (Hypothesis: CGs receiving CAP will report enhanced wellbeing and less time caregiving compared to the control intervention (3 and 6 months); and 3) Cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions (3 and 6 months; Hypothesis: CAP will be cost effective compared to the control intervention at each test occasion). Five exploratory aims will evaluate treatment effects on psychotropic medication use and other troublesome behaviors, if effects differ by cognitive status, if CGs receiving CAP use activities at 6 months and with what frequency, how time gained is spent, and if frequency/duration of treatment and activity use affects outcomes. If proven efficacious and cost effective, CAP has potential to transform clinical practice by offering a proven nonpharmacologic treatment for agitation of PwDs at home. This trial addresses a critical clinical need and public health priority identified by recent legislative activity. Objectives Our primary study aim evaluates the immediate effect of CAP on agitation at 3 months. Our hypothesis is that PwD receiving CAP will manifest a lower caregiver rated frequency and severity score on the Neuropsychiatric Inventory-(NPI) subscales of agitation+aggression (21 items), compared to those in the control intervention. Three secondary aims are to evaluate: 1) effects of CAP at 6 months on agitation and quality of life in patients. Hypothesis: Patients receiving CAP will manifest lower caregiver rated frequency and severity scores on the NPI-C agitation + aggression subscales and better quality of life in comparison to patients receiving the control intervention from baseline to 6 months; 2) effects of CAP at 3 and 6 months on CG wellbeing, (burden, skill acquisition, efficacy using activities), and time spent providing care. Hypothesis: Caregivers receiving CAP will report enhanced wellbeing and less time caregiving compared to those in the control intervention at 3 and at 6 months; and 3) cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions at 3 and 6 months. Hypothesis: CAP will be cost effective compared to the control intervention at each test occasion. To further understand treatment effects and enhance translation, we propose exploratory aims to evaluate: 1) Impact of CAP on psychotropic medication use in treatment and control conditions at 3 and 6 months by comparing proportion of PwD who require dose increases or incident use of psychotropic medications (negative outcome) and proportion of PwD who reduce or eliminate medication use because agitation improved (positive outcome); 2) Whether treatment effect on agitation differs at 3 and 6 months by cognitive status; 3) Whether CAP reduces total NPI scores as rated by CGs at 3 and 6 months, 4) If at 6-months CGs receiving CAP are using prescribed activities and with what frequency; and how CGs use any personal time gained; and 5) Extent to which treatment receipt and enactment (frequency/duration of sessions and use of activities) affects NPI-C scores. If proven efficacious and cost effective, CAP has potential to transform the current paradigm of dementia care that relies primarily on the pharmacologic management of agitation. It will offer clinicians and families a proven nonpharmacologic approach to enhance quality of life that can be replicated, has reimbursement potential, and resonates with medical treatment guidelines and health care reform efforts aimed at reducing pharmacologic use and helping older adults be cared for at home. Background This proposed trial specifically builds upon and extends the pilot phase testing of the proposed intervention with 60 dyads (NIMH R21 grant # R21 MH069425). This pilot phase evaluated program acceptability, identified behaviors most responsive, and evaluated magnitude of change for NPS and CG burden. Dyads were interviewed at baseline, randomized to intervention or wait-list control, and then reassessed at 4-months. After 4-months, the wait-list control group received the intervention and was reevaluated at 8 months (within group comparison 4 to 8 months). Main outcomes: At 4-months, a statistically significant treatment effect was found for frequency of NPS overall (p=.010; Cohen's d=.72) using the 16-item Agitated Behavior Inventory for dementia. Specifically, 77% of CGs in treatment reported improvements in NPS compared to 40% in the wait-list group; 23% in treatment reported worsening of NPS compared to 60% in wait-lists. As untreated agitation worsens over time in a significant proportion of patients, our pilot data suggests that worsened agitation was less common in the intervention group; the intervention also appeared to help reduce likelihood of worsening in patients whose agitation was destined to worsen without treatment. It appears unlikely that the intervention caused an adverse effect of worsening. However, as this is a possibility, it is listed in the consent form as a possible risk. Reductions for intervention group also occurred for specific behaviors reflecting agitation and behaviors of most concern to this CG sample; shadowing (p=.003, Cohen's d=3.10), and repetitive questioning (p=.023, Cohen's d=1.22), with slight increases (worsening) found for the control group. As shown in Figure 2, we also found a statistically significant reduction in prevalence of caregivers reporting agitation (p=.014, Cohen's d=.75); 14.8% in treatment vs. 44.8% in control reported PwD agitation at 4 months. A similar pattern was found for argumentation (p=.010, Cohen's d=.77). Also, CG in treatment reported that PwD demonstrated better engagement (p=.029, Cohen's d=.61), more pleasure (p=.045, Cohen's d=.690), and improved ability to keep positively busy (p=.017, Cohen's d=.71). Equally significant were reductions in CG objective burden as measured by NIH REACH vigilance items hours "doing things" for PwD (p=.005, Cohen's d=1.14); and hours "on duty" (p=.001, Cohen's d=1.01) with those in intervention reporting 5 hours less and those in control reporting spending 3 hours more on duty. Control group participants demonstrated similar benefits from 4 to 8 months. Medication Use: Of 60 PwD, 78.3% were on an anti-dementia medication (cholinesterase inhibitor or memantine), 32% were on psychotropic medication for NPS, and 45% were on antidepressants at study entry. Use of medications did not impact the primary outcome (e.g., frequency of behavioral symptoms). In separate regression analyses, we entered baseline use/non-use of 3 medication-types (e.g., anti-depressant, other psychotropic medication, and anti-dementia medications) as a predictor and found no impact on treatment outcome or effect size. This shows that medications are common, yet NPS persist. It also suggests the importance of assuring that PwD are on a stabilized dose prior to entering a trial so that treatment effects are not confounded by medication use. Cognitive Status: We found no difference in treatment effect by cognitive status: both high (\>10) and low (\< 10) MMSE groups benefited similarly with regard to the reduction of behavioral frequency. However, the high MMSE group also showed a reduction in the number of behaviors occurring at 4 months (p=.028). Cost: We also calculated preliminary incremental cost-effectiveness ratios (ICER), expressed as cost to bring about one additional unit of benefit measured by CG hours per day "doing things" and hours per day "being on duty" and decision tree and Monte Carlo analyses tested robustness of economic models. Average intervention cost was $941.63 per dyad. ICER showed that CGs in treatment saved one extra hour per day "doing things" at a cost of $2.37 per day; and one extra hour per day "being on duty" at a cost of $1.10 per day. Monte Carlo showed that the intervention was cost-effective 79.2% of the time for "doing things" and 79.6% of the time for "being on duty." Varying cost assumptions did not change cost-effectiveness. In summary, this pilot phase demonstrated proof of concept; high acceptability by PwD and CGs, preliminary positive outcomes, preliminary cost effectiveness, and that benefits were for PwD agitation and no adverse events. It also provides guidance for trial design considerations including importance of assuring dyads on medications have a stabilized dose prior to study enrollment and evaluating relationship of cognitive status to outcomes. Our proposed trial advances this pilot phase by: a) testing efficacy with a larger, diverse sample that will be well characterized as to diagnosis, disease severity, and behaviors using standard clinical assessments, b) comparing CAP to a control intervention condition receiving equivalent attention and social contact, controlling for unknown effects of empathy, validation and attention provided in CAP; c) examining cost effectiveness prospectively from a societal perspective, and d) evaluating a broad range of other outcomes and moderators (dose, intensity, activity use) to support future translational efforts. ### Conditions Module **Conditions:** - Dementia **Keywords:** - Agitation - Dementia - Alzheimer's Disease - Neuropsychiatric Behaviors ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 250 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The Tailored Activity Program unfolds over 3 phases: Phase I (sessions 1-2) involves assessment of Person with Dementia (PwD)capacity and interests, caregiver (CG) interactions and the physical environment and CG education. Phase II (sessions 3-6) involves identifying and implementing 3 "Activity Prescriptions" tailored to PwD's cognitive and interest profile using an algorithmic guide. The prescription summarizes PwD capabilities in lay language, identifies the activity and a specific activity goal, and provides specific instructions for introducing the activity. CGs are trained to integrate activities in daily care. Also provided are simple deep breathing stress reduction techniques to address CG upset. Phase III (sessions 7-8) involves instructing CGs in simplifying activities for future cognitive declines and applying simplification principles to other care challenges. **Intervention Names:** - Behavioral: Tailored Activity Program **Label:** Tailored Activity Program **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This arm receives 6 in-home and 2 brief telephone education sessions. Each contact is structured to provide helpful education. Sessions include information on home safety, fall risk assessment, talking to your doctor, advanced planning, identifying resources, and caring for the caregiver (CG). Each session is prescriptive and designed to maximize attention; yet, sessions will not involve any component of the intervention group. To engage the person with dementia (PwD), the interventionist will socially engage the person briefly in select sessions. Time spent with CG and PwD in the control group is comparable to that for intervention dyads. **Intervention Names:** - Other: Home Safety and Education Program **Label:** Home Safety and Education Program **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Tailored Activity Program **Description:** TAP is designed to tap into spared or residual abilities and provide an environment supportive of these abilities. Activities are selected that build on preserved capabilities, long-term interests and procedural memory, but which do not tax areas of cognition that are most impaired (e.g., memory, new learning). Activities selected are simplified (1 to 2 vs multiple, complex steps), thereby minimizing errors. The activity environment is set up to provide auditory or tactile cues to facilitate recall and guide initiation and sequencing. By grading activities to match PwD capabilities, the interventionist minimizes demand that may heighten stress (e.g., high functioning individuals are introduced to more goal-directed, multi-step activities, whereas lower functioning individuals are introduced to activities involving repetitive motion (e.g., washing windows, folding towels, placing materials in a bin) and integrate multi-sensory stimulation (e.g., soft music, objects pleasant to touch). **Name:** Tailored Activity Program **Other Names:** - TAP - CAP **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Home Safety and Education Program **Description:** The control group intervention is designed to control for the nonspecific elements of TAP such as social engagement with PwD and CG which may affect outcomes. It is a fully-structured, nondirective, supportive education approach that conveys empathy, respect and specific disease education elements of which have been tested in other trials. Unlike TAP, this group contains no active elements beyond its nonspecific components, has no long-lasting treatment effects, and no theoretical basis to support an effect on agitation. It is delivered by a trained research team member who uses active listening, open questioning, reflecting back, and summation with CGs. **Name:** Home Safety and Education Program **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Frequency by severity of agitated and aggressive behaviors measured by the Neuropsychiatric Inventory (NPI) as reported by the primary caregiver. Frequency for severity for both is calculated and then the numbers are added together. **Measure:** Frequency by severity of Agitated and Aggressive Behavior in person with dementia **Time Frame:** 3 months #### Secondary Outcomes **Description:** Frequency of agitated behaviors is measured by the Neuropsychiatric Inventory (NPI) as reported by the primary caregiver. **Measure:** Frequency of behavioral symptoms in person with dementia **Time Frame:** 6 months **Description:** Quality of life is measured with the Perceived Change for the Better Index as rated by the caregiver. **Measure:** Quality of life in person with dementia rated by caregiver **Time Frame:** 3 and 6 months **Description:** Quality of life is measured with the Quality of Life index completed by the person with dementia. **Measure:** Quality of life in person with dementia rated by person with dementia **Time Frame:** 3 and 6 months **Description:** Caregiver wellbeing will be measured with the Zarit burden scale. **Measure:** Caregiver wellbeing **Time Frame:** 3 and 6 months **Description:** Time spent providing care will be measured with the RUD 3.0 supplemented with the SURFS and Health Utility Index. **Measure:** Time spent caregiving **Time Frame:** 3 and 6 months **Description:** Cost effectiveness by intervention cost will be calculated from interventionist payroll and mileage, also by cost of supplies for intervention **Measure:** Cost effectiveness by intervention cost **Time Frame:** 3 and 6 months **Description:** Cost effectiveness will be measured by hospital stays, use of services, time to nursing home or death, medications and caregiver costs. **Measure:** Cost effectiveness by medical costs **Time Frame:** 3 and 6 months **Description:** Cost effectiveness will be measured by quality of life measures (EuroQol-5D). **Measure:** Cost effectiveness by quality of life **Time Frame:** 3 and 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Inclusion criteria pertain to both the person with dementia (PwD) and the caregiver (CG) such that if either is eligible but the other is not, the dyad is not enrolled. * PwD and caregiver are English speaking * Diagnosed with probable dementia * PwD is able to participate in at least 2 activities of daily living (bathing, dressing, grooming, toileting, transferring from bed to chair) * Person with dementia exhibits agitated or aggressive behaviors * If PwD is on a psychotropic medication he/she must be on a stable dose for at least 60 days * CG is at least 21 years old * CG lives with or within 5 miles of the person with dementia * CG is accessible by telephone to schedule interviews and sessions * CG is planning to live in the area for at least 6 months * If the CG is on a psychotropic medication he/she must be on a stable dose for at least 60 days Exclusion Criteria:Exclusion criteria pertain to both the person with dementia and the caregiver such that if either is eligible but the other is not, the dyad is not enrolled. * PwD has a history of schizophrenia or bipolar disorder * Dementia is secondary to probable head trauma * PwD is not responsive to environment (e.g., unable to understand short commands or recognize a person coming in/out of the room). * the CG is currently involved in another clinical trial of psychosocial or educational interventions * the CG is planning to place PwD in a nursing home within 6 months. * dyads will be excluded if either CG or PwD: 1) has a terminal illness with life expectancy \< 6 months, 2) is in active treatment for cancer, or 3) has had \> 3 acute medical hospitalizations in past year. **Healthy Volunteers:** True **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Baltimore **Country:** United States **Facility:** Johns Hopkins University School of Nursing, Center for Innovative Care in Aging **State:** Maryland **Zip:** 21205 #### Overall Officials **Official 1:** **Affiliation:** Johns Hopkins University **Name:** Laura N Gitlin, Ph.D **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Gitlin LN, Hodgson N, Jutkowitz E, Pizzi L. The cost-effectiveness of a nonpharmacologic intervention for individuals with dementia and family caregivers: the tailored activity program. Am J Geriatr Psychiatry. 2010 Jun;18(6):510-9. doi: 10.1097/JGP.0b013e3181c37d13. **PMID:** 20847903 **Citation:** Jutkowitz E, Gitlin LN, Pizzi LT. Evaluating willingness-to-pay thresholds for dementia caregiving interventions: application to the tailored activity program. Value Health. 2010 Sep-Oct;13(6):720-5. doi: 10.1111/j.1524-4733.2010.00739.x. Epub 2010 Jun 7. **PMID:** 20561331 **Citation:** Gitlin LN, Winter L, Vause Earland T, Adel Herge E, Chernett NL, Piersol CV, Burke JP. The Tailored Activity Program to reduce behavioral symptoms in individuals with dementia: feasibility, acceptability, and replication potential. Gerontologist. 2009 Jun;49(3):428-39. doi: 10.1093/geront/gnp087. Epub 2009 May 6. **PMID:** 19420314 **Citation:** Gitlin LN, Winter L, Burke J, Chernett N, Dennis MP, Hauck WW. Tailored activities to manage neuropsychiatric behaviors in persons with dementia and reduce caregiver burden: a randomized pilot study. Am J Geriatr Psychiatry. 2008 Mar;16(3):229-39. doi: 10.1097/JGP.0b013e318160da72. **PMID:** 18310553 **Citation:** Gitlin LN, Marx K, Piersol CV, Hodgson NA, Huang J, Roth DL, Lyketsos C. Effects of the tailored activity program (TAP) on dementia-related symptoms, health events and caregiver wellbeing: a randomized controlled trial. BMC Geriatr. 2021 Oct 20;21(1):581. doi: 10.1186/s12877-021-02511-4. **PMID:** 34670502 **Citation:** Regier NG, Hodgson NA, Gitlin LN. Neuropsychiatric symptom profiles of community-dwelling persons living with dementia: Factor structures revisited. Int J Geriatr Psychiatry. 2020 Sep;35(9):1009-1020. doi: 10.1002/gps.5323. Epub 2020 May 26. **PMID:** 32363605 **Citation:** Jutkowitz E, Scerpella D, Pizzi LT, Marx K, Samus Q, Piersol CV, Gitlin LN. Dementia Family Caregivers' Willingness to Pay for an In-home Program to Reduce Behavioral Symptoms and Caregiver Stress. Pharmacoeconomics. 2019 Apr;37(4):563-572. doi: 10.1007/s40273-019-00785-6. **PMID:** 30877638 **Citation:** Gitlin LN, Piersol CV, Hodgson N, Marx K, Roth DL, Johnston D, Samus Q, Pizzi L, Jutkowitz E, Lyketsos CG. Reducing neuropsychiatric symptoms in persons with dementia and associated burden in family caregivers using tailored activities: Design and methods of a randomized clinical trial. Contemp Clin Trials. 2016 Jul;49:92-102. doi: 10.1016/j.cct.2016.06.006. Epub 2016 Jun 21. **PMID:** 27339865 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000020820 - Term: Dyskinesias - ID: D000009461 - Term: Neurologic Manifestations - ID: D000011596 - Term: Psychomotor Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000096762 - Term: Aberrant Motor Behavior in Dementia - ID: D000001526 - Term: Behavioral Symptoms ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6904 - Name: Dementia - Relevance: HIGH - As Found: Dementia - ID: M3885 - Name: Alzheimer Disease - Relevance: LOW - As Found: Unknown - ID: M14452 - Name: Psychomotor Agitation - Relevance: HIGH - As Found: Agitation - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M22574 - Name: Dyskinesias - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M14453 - Name: Psychomotor Disorders - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M3259 - Name: Aberrant Motor Behavior in Dementia - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: T2192 - Name: Familial Alzheimer Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003704 - Term: Dementia - ID: D000011595 - Term: Psychomotor Agitation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04946279 **Brief Title:** Decision Aid for the Improvement of Decision-Making in Patients With Non-small Cell Lung Cancer **Official Title:** Improving Decision-Making Encounters in Lung Cancer (I DECide): A Low-Literacy Conversation Tool #### Organization Study ID Info **ID:** STUDY00020688 #### Organization **Class:** OTHER **Full Name:** OHSU Knight Cancer Institute #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2021-05887 **Type:** REGISTRY **Domain:** OHSU Knight Cancer Institute **ID:** STUDY00020688 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-14 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2020-08-07 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2021-06-30 **Type:** ACTUAL **Study First Submit Date:** 2021-06-23 **Study First Submit QC Date:** 2021-06-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Oregon Health and Science University **Class:** UNKNOWN **Name:** ATS Foundation **Class:** UNKNOWN **Name:** Hildegard Lamfrom Endowment **Class:** OTHER **Name:** Medical Research Foundation, Oregon #### Lead Sponsor **Class:** OTHER **Name:** OHSU Knight Cancer Institute #### Responsible Party **Investigator Affiliation:** OHSU Knight Cancer Institute **Investigator Full Name:** Donald R Sullivan, MD, MA, MCR **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This clinical trial refines and tests the effect of a decision aid in improving decision-making in patients with non-small cell lung cancer. Patients with cancer want to be informed about their diagnoses, treatment procedures and goals of treatment. They also seek active roles in decision-making. Shared decision-making (SDM) is the process of clinician and patient jointly participating in a health decision after discussing the options, benefits and harms, and considering the patient's values, preferences, and circumstances. SDM can improve patient involvement in decision making, satisfaction, health care quality, and quality of life. Decision aids can improve patient knowledge, create more realistic outcome expectations; reduce decisional conflict, distress, depression and uncertainty; and improve physician-patient communication and quality of life, compared with no decision aid. This trial's main aim is to evaluate the feasibility and efficacy of a decision aid in patients with non-small cell lung cancer. **Detailed Description:** PRIMARY OBJECTIVES: I. Refine a conversation tool among patients with lung cancer by conducting prototype testing in an iterative process. II. Conduct a trial at two comprehensive cancer treatment centers representing academic and Veterans Affairs medical centers. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive the conversation tool. ARM II: Patients receive usual care. Patients in both arms are followed up within 4-8 weeks after baseline to complete a second questionnaire. ### Conditions Module **Conditions:** - Lung Non-Small Cell Carcinoma - Stage I Lung Cancer AJCC v8 - Stage II Lung Cancer AJCC v8 - Stage III Lung Cancer AJCC v8 - Stage IV Lung Cancer AJCC v8 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 98 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive the conversation tool. **Intervention Names:** - Other: Informational Intervention - Other: Questionnaire Administration **Label:** Arm I (conversation tool) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients receive usual care. **Intervention Names:** - Other: Best Practice - Other: Questionnaire Administration **Label:** Arm II (usual care) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm II (usual care) **Description:** Receive usual/standard of care **Name:** Best Practice **Other Names:** - standard of care - standard therapy **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Arm I (conversation tool) **Description:** Receive conversation tool **Name:** Informational Intervention **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Arm I (conversation tool) - Arm II (usual care) **Description:** Ancillary studies - Baseline and follow-up questionnaires **Name:** Questionnaire Administration **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The number of patients enrolled divided by the number of patients offered enrollment. **Measure:** Feasibility of the conversation tool **Time Frame:** At enrollment **Description:** The number of participants who completed the conversation tool divided by the number of participants who began the conversation tool. **Measure:** Acceptability of the conversation tool **Time Frame:** At enrollment #### Secondary Outcomes **Description:** Assessed using the Hospital Anxiety and Depression Scale. **Measure:** Anxiety **Time Frame:** From enrollment to the end of follow-up at 8 weeks **Description:** Assessed using the Decisional Conflict Scale. **Measure:** Decisional conflict **Time Frame:** At the end of follow-up at 8 weeks **Description:** Assessed using the Decisional Regret Scale. **Measure:** Decisional Regret **Time Frame:** At the end of follow-up at 8 weeks **Description:** Assessed using the Perceived Involvement in Care Scale. **Measure:** Perceived involvement in care **Time Frame:** At the end of follow-up at 8 weeks **Description:** Assessed using the Shared Decision Making Questionnaire. **Measure:** Shared decision-making quality **Time Frame:** At the end of follow-up at 8 weeks **Description:** Assessed using the Control Preferences Scale. **Measure:** Decision making involvement **Time Frame:** From enrollment to the end of follow-up at 8 weeks **Description:** Assessed using the Decision Self-Efficacy Scale. **Measure:** Self-efficacy **Time Frame:** From enrollment to the end of follow-up at 8 weeks **Description:** Assessed using electronic medical record (EMR). **Measure:** Values-treatment concordance **Time Frame:** From enrollment to the end of follow-up at 8 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * PART I: Completed treatment for suspected or confirmed stage I-IV non-small cell lung cancer (NSCLC) * PART I: English fluency * PART II: Undergoing diagnostic work-up for suspected stage I-IV NSCLC * PART II: English fluency * PART II: \> 6-month life expectancy * PART II: Score of \> 3 on the 6-Item Screener for Cognitive Impairment **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Portland **Country:** United States **Facility:** OHSU Knight Cancer Institute **State:** Oregon **Zip:** 97239 **Location 2:** **City:** Portland **Country:** United States **Facility:** Portland VA Medical Center **State:** Oregon **Zip:** 97239 #### Overall Officials **Official 1:** **Affiliation:** OHSU Knight Cancer Institute **Name:** Donald Sullivan **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: Lung Non-Small Cell Carcinoma - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03412279 **Brief Title:** Validation of Hausa Oswestry Disability Index, Numeric Pain Rating Scale, Roland-Morris Disability Questionnaire, SF-12 Health Survey, Pain Catastrophizing Scale, Fear-Avoidance Beliefs Questionnaire,Global Rating of Change Scale and Back Beliefs Questionnaire in Low Back Pain Patients **Official Title:** Translation, Cross-cultural Adaptation, and Psychometric Properties of the Hausa Versions of the Oswestry Disability Index, Numeric Pain Rating Scale, Roland-Morris Disability Questionnaire, SF-12 Health Survey, Pain Catastrophizing Scale, Fear-Avoidance Beliefs Questionnaire, Global Rating of Change Scale and Back Beliefs Questionnaire in Patients With Low Back Pain #### Organization Study ID Info **ID:** PPT/00009 #### Organization **Class:** OTHER **Full Name:** Bayero University Kano, Nigeria ### Status Module #### Completion Date **Date:** 2019-01-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-06-28 **Type:** ACTUAL **Last Update Submit Date:** 2019-06-26 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-01-31 **Type:** ACTUAL #### Start Date **Date:** 2018-01-01 **Type:** ACTUAL **Status Verified Date:** 2019-06 #### Study First Post Date **Date:** 2018-01-26 **Type:** ACTUAL **Study First Submit Date:** 2018-01-15 **Study First Submit QC Date:** 2018-01-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Bayero University Kano, Nigeria #### Responsible Party **Investigator Affiliation:** Bayero University Kano, Nigeria **Investigator Full Name:** Aminu A. Ibrahim **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Oswestry Disability Index (ODI), Numeric Pain Rating Scale, Roland-Morris Disability Questionnaire (RMDQ), SF-12 Health Survey, Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ), Global Rating of Change Scale and Back Beliefs Questionnaire (BBQ) are important and widely used validated patient self-reported measures commonly used in clinical trials and health research involving patients with low back pain (LBP). However, to date, validated Hausa versions of these tools are unavailable for use despite not only Hausa language is commonly spoken in Nigeria but in other parts of the world. The purpose of this study is to perform, using evidence-based guidelines, translation, cultural adaptation and validation of the ODI, NPRS, RMDQ, SF-12 health survey, FABQ, PCS, GROC and BBQ into Hausa language among patients with LBP in Northern Nigeria. **Detailed Description:** This study will test the psychometric properties (i.e validity; reliability, and ceiling effect) of the ODI-H, NPRS, RMDQ-H, SF-12-H, FABQ-H, PCS-H, GROC and BBQ-H in Hausa-speaking patients with LBP. Rural and urban participants with LBP will be recruited purposively. Copies of the translated Hausa versions of the NPRS, ODI, RMDQ, SF-12, FABQ, PCS, BBQ as well as VAS for pain and disability will be self or interviewer-administered. Lumbopelvic mobility using finger-floor distance test (FFD) will be also measured. The Hausa versions of the ODI, NPRS, RMDQ, SF-12, FABQ, PCS, GROC and BBQ will be administered again a week after. Data will be analysed using descriptive, correlation, and factorial analysis on IBM SPSS (version 23.0) at alpha level of 0.05. ### Conditions Module **Conditions:** - Chronic Low Back Pain **Keywords:** - Chronic Low Back Pain - Oswestry Disability Index - Numeric Pain Rating Scale - Roland Morris Disability Questionnaire - SF-12 Health Survey - Fear-Avoidance Beliefs Questionnaire - Pain Catastrophizing Scale - Global Rating of Change Scale - Back Beliefs Questionnaire ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 200 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Initial evaluation involves the application of Hausa ODI, NPRS, RMDQ, SF-12, PCS, GROC, BBQ, VAS for pain and disability, and FFD. **Name:** Application of the initial evaluation **Type:** BEHAVIORAL #### Intervention 2 **Description:** Application of the Hausa versions of ODI, NPRS, RMDQ, SF-12, PCS, GROC and BBQ one week after initial evaluation **Name:** Final application of instruments **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Functional disability will be measured by the Hausa Oswestry disability index (ODI-H). The questionnaire consists of 10 items with each item having six statements. All scores are summed, then multiplied by two to obtain the index (range 0 to 100) with higher score indicating greater disability. **Measure:** Change in functional disability **Time Frame:** Baseline and 1 week after baseline **Description:** Pain intensity will be measured by the Hausa Numeric Pain Rating Scale (NPRS-H). The score ranges from 0 to 10, with 0 indicating "No Pain" and 10 "Worst Imaginable Pain". **Measure:** Change in pain intensity **Time Frame:** Baseline and 1 week after baseline **Description:** Functional disability will be measured by the Hausa Roland-Morris Disability Questionnaire (RMDQ-H). The score ranges from 0 to 24, with 0 indicating no disability and 24 maximum disability. **Measure:** Change in functional disability **Time Frame:** Baseline and 1 week after baseline **Description:** Quality of life will be measured using the Hausa SF-12 Health Hurvey (SF-12-H). The questionnaire consists of 12 items questioned weighted and summed to provide physical and mental health scores (PCS and MCS). The two composite scores are computed using the scores on twelve questions that range from 0 to 100, with higher score indicating better health. **Measure:** Change in quality of life **Time Frame:** Baseline and 1 week after baseline **Description:** Fear-avoidance beliefs will be measured by the Hausa fear avoidance beliefs **Measure:** Change in fear-avoidance beliefs **Time Frame:** Baseline and 1 week after baseline **Description:** Pain catastrophization will be measured by the Hausa Pain Catastrophizing Scale (PCS-H). The scale consists of 13 items rated on 5-point ordinal scale (0-5).The total score ranges from 0-52 with higher score indicating more catastrophic thoughts. **Measure:** Change in pain catastrophization **Time Frame:** Baseline and 1 week after baseline **Description:** Back pain beliefs will be evaluated by the Hausa Back Beliefs Questionnaire (BBQ-H). The questionnaire consists of 14 items with 9 items ranked on a 5 point scale and used to calculate a final score from 9 to 45. Higher scores are indicative of better LBP beliefs and indicate the potential of a better ability to cope with LBP. **Measure:** Change in back beliefs **Time Frame:** Baseline and 1 week after baseline **Description:** Perceived recovery will be evaluated by the Hausa Global Rating Change of Scale (GROC-H). The scale is an 11-point scale ranging from -5 to +5 with a mid-point (0) representing " no change", a left anchor (-5) representing "Very much Worse" and a right anchor (+5) representing "Completely Recovered". **Measure:** Change in perceived recovery **Time Frame:** Baseline and 1 week after baseline #### Secondary Outcomes **Description:** Pain Intensity will be measured by 100 mm Visual Analogue Scale (VAS-P), in which 0 represents "no pain" and 10 represents "worst pain imaginable". **Measure:** Change in pain Intensity **Time Frame:** Baseline only **Description:** Disability will be measured by 100 mm Visual Analogue Scale (VAS-D), in which 0 represents "no disability" and 10 represents "severe disability". **Measure:** Change in disability **Time Frame:** Baseline only **Description:** The finger-floor distance test (FFD) measures mobility of both the whole spine and the pelvis in the overall motion of bending forward. **Measure:** Change in mobility of the spine and pelvis **Time Frame:** Baseline only ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male and female between 18 and 70 years old. * Nonspecific low back pain lasting for more than 12 weeks. * Resident in the selected rural and urban communities in Kano State Nigeria. * Ability to read/understand English or Hausa language. Exclusion Criteria: * Previous history of back surgery. * Spine pathology (e.g. tumor, infection, fracture) * Severe cognitive impairment * Impaired capacity to be interviewed * Current pregnancy **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adults with CLBP attending either rural or urban physiotherapy clinics in Kano State, Northern Nigeria. ### Contacts Locations Module #### Locations **Location 1:** **City:** Kano **Country:** Nigeria **Facility:** Murtala Muhammad Specialist Hospital, Wudil General Hospital, Rano General Hospital, Kura General Hospital, and Dawakin-Kudu General Hospital **Zip:** 700 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4714 - Name: Back Pain - Relevance: HIGH - As Found: Back Pain - ID: M19433 - Name: Low Back Pain - Relevance: HIGH - As Found: Low Back Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001416 - Term: Back Pain - ID: D000017116 - Term: Low Back Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02559479 **Brief Title:** A Study to Assess the Effect of a Normal vs. High Protein Diets in Carbohydrates Metabolism in Obese Subjects With Diabetes or Prediabetes **Official Title:** A Study to Assess the Effect of a Normal vs. High Protein Diets in Carbohydrates Metabolism in Obese Subjects With Diabetes or Prediabetes #### Organization Study ID Info **ID:** CEICA;PI/15/0183 #### Organization **Class:** OTHER_GOV **Full Name:** Instituto Aragones de Ciencias de la Salud ### Status Module #### Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2016-12-02 **Type:** ESTIMATED **Last Update Submit Date:** 2016-12-01 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Start Date **Date:** 2015-09 **Status Verified Date:** 2016-12 #### Study First Post Date **Date:** 2015-09-24 **Type:** ESTIMATED **Study First Submit Date:** 2015-09-22 **Study First Submit QC Date:** 2015-09-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Instituto Aragones de Ciencias de la Salud #### Responsible Party **Investigator Affiliation:** Instituto Aragones de Ciencias de la Salud **Investigator Full Name:** Fernando Civeira **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of the study is to assess the effect of low-calorie diets with normal (18%) vs. high (35%) protein (mainly coming from animal source) composition on body weight and carbohydrates metabolism in overweight and obese subjects with pre-diabetes or diabetes. A dietary intervention is carried out during 6 months in 100 subjects who are individually randomized to an energy-restricted diet with two types of macronutrients composition: 1) 35% protein, 30% fat and 35% carbohydrates and 2) 18% protein, 30% fat and 52% carbohydrates. Around 80% of total protein in diet comes from animal source (of whom around 40% from lean red meat). Subjects are provided with weekly menus and different recipes to use them as part of the diet. Monitoring visits with the nutritionist will be performed every 15 days. At the beginning of the study, after 3 and 6 months, the following parameters are determined: anthropometric (weight, waist circumference, body mass index and body composition), blood pressure, dietary (72-hours dietary registry) and exercise and biochemical analysis (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoproteins A1 and B, iron, transferring, ferritin, uric acid, glucose, HbA1c, insulin, adiponectin and resistin). Urine samples are also collected to assess microalbuminuria and ureic nitrogen. ### Conditions Module **Conditions:** - Weight Loss - Obesity - Diabetes - Diet, Reducing - Carbohydrates - Protein ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Energy-restricted diet wit the following composition: 18% protein, 30% fat and 52% carbohydrates **Intervention Names:** - Behavioral: Weight loss interventional study with a low-calorie 18%-protein diet **Label:** 18%-Protein diet **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Energy-restricted diet wit the following composition: 35% protein, 30% fat and 35% carbohydrates **Intervention Names:** - Behavioral: Weight loss interventional study with a low-calorie 35%-protein diet **Label:** 35%-Protein diet **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 18%-Protein diet **Name:** Weight loss interventional study with a low-calorie 18%-protein diet **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - 35%-Protein diet **Name:** Weight loss interventional study with a low-calorie 35%-protein diet **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** Change in glucose. **Time Frame:** After 3 and 6 months of intervention. **Measure:** Change in glycated hemoglobin. **Time Frame:** After 3 and 6 months of intervention. **Measure:** Change in insulin resistance (HOMA index). **Time Frame:** After 3 and 6 months of intervention. #### Secondary Outcomes **Measure:** Change in body weight. **Time Frame:** After 3 and 6 months of intervention. **Measure:** Change in body composition. **Time Frame:** After 3 and 6 months of intervention. **Measure:** Change in waist circumference. **Time Frame:** After 3 and 6 months of intervention. **Measure:** Change in lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, non HDL cholesterol, triglycerides and apolipoproteins). **Time Frame:** After 3 and 6 months of intervention. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age: 18-70 years old. * Body mass index between 27.5 - 40. * Steady weight (± 4 kg) in the last 2 months. * Glycated hemoglobin between 6 - 7%. Exclusion Criteria: * Anti-diabetic drugs (oral or subcutaneous) in the last 2 months. * Lipid-lowering drugs in the last 2 months. * Gouty arthritis in the last 2 years or uric acid \> 735 mg/dl. * Presence of uncontrolled endocrinological pathology (including hypothyroidism). * Hepatic chronic disease (glomerular filtration rate \< 45 ml/min). * Renal, inflammatory or tumoral diseases. * Drugs which could interfere in glucose or lipid metabolism such as androgens, corticosteroids (except for those with topic administration) and estrogen replacement therapy. * Intake of functional foods with plant sterols in the past 6 weeks. * High alcohol intake (\> 30 g per day). * Any serious disease which involves less than 1 year life expectancy or, in investigators judgment, limit the follow-up of an homogeneous diet throughout the study. * Pregnancy or intention of pregnancy during the study. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** civeira@unizar.es **Name:** Fernando Civeira, MD, PhD **Phone:** +34 976765500 **Phone Ext:** 2884 **Role:** CONTACT **Contact 2:** **Email:** rmateo.iacs@aragon.es **Name:** Rocio Mateo-Gallego, RD, PhD **Role:** CONTACT #### Locations **Location 1:** **City:** Zaragoza **Contacts:** ***Contact 1:*** - **Email:** rmateo.iacs@aragon.es - **Name:** Rocio Mateo-Gallego, RD, PhD - **Phone:** +34 976765500 - **Phone Ext:** 2895 - **Role:** CONTACT ***Contact 2:*** - **Email:** vito2911@hotmail.com - **Name:** Victoria Marco-Benedí, RD - **Phone:** +34 976765500 - **Phone Ext:** 2895 - **Role:** CONTACT **Country:** Spain **Facility:** Fernando Civeira **Status:** RECRUITING **Zip:** 50009 #### Overall Officials **Official 1:** **Affiliation:** Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis; Hospital U. Miguel Servet; IIS Aragón **Name:** Fernando Civeira, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** YES ### References Module #### References **Citation:** Marco-Benedi V, Perez-Calahorra S, Bea AM, Lamiquiz-Moneo I, Baila-Rueda L, Cenarro A, Civeira F, Mateo-Gallego R. High-protein energy-restricted diets induce greater improvement in glucose homeostasis but not in adipokines comparing to standard-protein diets in early-onset diabetic adults with overweight or obesity. Clin Nutr. 2020 May;39(5):1354-1363. doi: 10.1016/j.clnu.2019.06.005. Epub 2019 Jun 15. **PMID:** 31255349 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000001836 - Term: Body Weight Changes - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M18102 - Name: Weight Loss - Relevance: HIGH - As Found: Weight Loss - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M14117 - Name: Prediabetic State - Relevance: HIGH - As Found: Prediabetes - ID: M20295 - Name: Glucose Intolerance - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M5115 - Name: Body Weight Changes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000011236 - Term: Prediabetic State - ID: D000015431 - Term: Weight Loss ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01334879 **Brief Title:** High Dose Intravitreal Ranibizumab for Recalcitrant Radiation Retinopathy **Official Title:** High Dose (2.0mg) Intravitreal Ranibizumab for Recalcitrant Radiation Retinopathy #### Organization Study ID Info **ID:** FVF4981S #### Organization **Class:** OTHER **Full Name:** The New York Eye Cancer Center ### Status Module #### Completion Date **Date:** 2012-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-10-02 **Type:** ESTIMATED **Last Update Submit Date:** 2014-09-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-11 **Type:** ACTUAL #### Start Date **Date:** 2011-05 **Status Verified Date:** 2014-09 #### Study First Post Date **Date:** 2011-04-13 **Type:** ESTIMATED **Study First Submit Date:** 2011-04-11 **Study First Submit QC Date:** 2011-04-12 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Genentech, Inc. #### Lead Sponsor **Class:** OTHER **Name:** The New York Eye Cancer Center #### Responsible Party **Investigator Affiliation:** The New York Eye Cancer Center **Investigator Full Name:** Paul T. Finger, MD **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study investigates the use of a high dose anti-VEGF agent for the treatment of radiation retinopathy in those patients who have recalcitrant disease. **Detailed Description:** This study is an open-label, Phase I study of intravitreally administered ranibizumab in subjects with radiation retinopathy. This is a single center, non-randomized, active treatment study involving 10 consecutive patients. This study will evaluate the safety and tolerability of a high dose (2.0 mg) intravitreal ranibizumab and its effect on regression of radiation retinopathy and mean change in visual acuity. ### Conditions Module **Conditions:** - Radiation Retinopathy **Keywords:** - radiation - retinopathy - anti-VEGF - eye ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 10 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 5 patients will receive intravitreal injections every 30 days (+/- 7 days) for the first 4 months and every month thereafter until month 12 (maximum of 12 injections) **Intervention Names:** - Drug: ranibizumab 2.0 mg **Label:** With Loading Doses **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** 5 patients will receive intravitreal ranibizumab every 30 days (+/- 7 days) on as needed basis based on the criteria defined in the study. **Intervention Names:** - Drug: ranibizumab 2.0 mg **Label:** Physician Discretion **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Physician Discretion - With Loading Doses **Description:** Intravitreal ranibizumab (2.0 mg) **Name:** ranibizumab 2.0 mg **Other Names:** - Lucentis **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** All subjects will be assessed at baseline, at 7 days after first injection, and monthly for adverse events. The primary outcome measures for safety and tolerability are: 1. incidence and severity of ocular adverse events, as identified by eye examination (including best corrected visual acuity testing) and 2. Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs **Measure:** Number of participants with adverse events (allergy, infection, or change in vital signs) **Time Frame:** Baseline, at day 7, then monthly #### Secondary Outcomes **Description:** This secondary outcome measure will evaluate the effect of ranibizumab in both groups (arms) on Regression of radiation retinopathy as measured by mean change in central retinal thickness as measured on optical coherence tomography (OCT) compared to baseline **Measure:** Number of participants with changes in central foveal thickness **Time Frame:** Monthly, Report at Month 12 **Description:** Each month each subject will be tested for best corrected visual acuity as compared to baseline. **Measure:** Number of participants with changes in visual acuity **Time Frame:** Monthly, Report at Month 12 **Description:** Each group (arm) will be assessed for the number of monthyl injections received through Month 12. **Measure:** Number of injections each group (arm) has received **Time Frame:** Monthly, Report at Month 12 **Description:** Evaluation of both arms on qualitative change in exudates, retinal hemorrhage, microaneurym and neovascularization) as seen on ophthalmoscopy/color photography and fluorescein angiography compared to baseline. **Measure:** Number of participants with qualitative changes in retinopathy on ophthalmoscopy and fluorescein angiography **Time Frame:** Monthly Report at Month 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria Subjects will be eligible if the following criteria are met: * Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 21 years * History of a clinical diagnosis of radiation retinopathy * Subjects who are at least 3 months and no more than 10 years from radiation therapy * History of prior treatment for radiation retinopathy with incomplete response (eg. persistent edema, presence of hemorrhage, presence of exudates, etc * ETDRS best corrected visual acuity of 20/400 or better in the study eye * Ability to return for all study visits Exclusion Criteria Subjects who meet any of the following criteria will be excluded from this study: * Pregnancy (positive pregnancy test) or lactation Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated * Participation in another simultaneous medical investigation or trial * Subject with significantly compromised visual acuity in the study eye due to concomitant ocular conditions. * Subjects who have undergone intraocular surgery within last 60 days. * Subjects who have had intravitreal anti-VEGF treatment within 30 days. * Subjects who have had intravitreal triamcinolone acetonide within 4 months. * Subjects who have had laser within 60 days. * Inability to obtain photographs to document CNV (including difficulty with venous access). * Subject with known adverse reaction to fluorescein dye. * Subject has a history of any medical condition which would preclude scheduled visits or completion of study. * Aphakia or absence of the posterior capsule in the study eye. Previous violation of the posterior capsule in the study eye is also excluded unless as a result of yttrium aluminum garnet (YAG) posterior capsulotomy in association with posterior chamber lens implantation.. * History of glaucoma filtering surgery in the study eye. * Concurrent use of more than two therapies for glaucoma. * Uncontrolled glaucoma in the study eye (defined as intraocular pressure \>30 mm Hg despite treatment with anti-glaucoma medication) * Inability to comply with study or follow-up procedure **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New York **Country:** United States **Facility:** The New York Eye Cancer Center **State:** New York **Zip:** 10065 #### Overall Officials **Official 1:** **Affiliation:** The New York Eye Cancer Center **Name:** Paul T Finger, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** Dr. Finger's Radiation Retinopathy Studies **URL:** http://www.ncbi.nlm.nih.gov/pubmed?term=radiation%20retinopathy%20Finger%20PT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14999 - Name: Retinal Diseases - Relevance: HIGH - As Found: Retinopathy - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012164 - Term: Retinal Diseases ### Intervention Browse Module - Ancestors - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000006131 - Term: Growth Inhibitors - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M472 - Name: Ranibizumab - Relevance: HIGH - As Found: Dysfunction - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069579 - Term: Ranibizumab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05827679 **Acronym:** ECAP **Brief Title:** Creation and Validation of a Clinical Evaluation Scale for Abdominal Condition of the Premature (ECAP) **Official Title:** Creation and Validation of a Clinical Evaluation Scale for Abdominal Condition of the Premature #### Organization Study ID Info **ID:** RNI 2022 COLNE #### Organization **Class:** OTHER **Full Name:** University Hospital, Clermont-Ferrand #### Secondary ID Infos **Domain:** ANSM **ID:** 2022-A02779-34 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2023-09-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-15 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-09-01 **Type:** ACTUAL #### Start Date **Date:** 2023-03-15 **Type:** ACTUAL **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2023-04-25 **Type:** ACTUAL **Study First Submit Date:** 2023-03-23 **Study First Submit QC Date:** 2023-04-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Clermont-Ferrand #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Every year in France, 60,000 children are born prematurely (before 37 weeks of amenorrhea), and present an immaturity of their various systems, in particular the digestive system. This can result in feeding intolerance, which is expressed by abdominal distension, regurgitation or vomiting, irregular transit and abdominal discomfort. This feeding intolerance influences the length of hospitalization and can lead to necrotising enterocolitis, a major complication. In the Neonatal Intensive Care Units of Clermont-Ferrand hospital center, abdominal massages have been performed by physiotherapists for several years in order to improve the condition of the digestive system. However, the indication for abdominal massage is very dependent on the caregivers in charge of the newborn and the evaluation of the abdominal condition remains subjective with a great variability between examiners. Thus, some newborns will receive massage multiple times a day while others will not. Developmental care is essential for these premature infants, especially to avoid over-stimulation. It is important not to add care, such as massage, if it is not needed. It is therefore essential to properly assess the digestive status of premature babies in order to determine whether they have feeding intolerance and whether they require treatment with abdominal massage. To date, the investigators have not found measurable criteria or existing scales that can describe the digestive status of newborns. The main objective of the study is therefore to create and validate a clinical assessment scale for the abdominal status of preterm infants. **Detailed Description:** This is an observational study with longitudinal follow-up regarding the validation of a scale that the investigators have created. Inclusions will be made when the patient arrives at the Clermont-Ferrand hospital center in the neonatal intensive care units. The patients will be evaluated daily from the 3rd day of life by the nurse, the physiotherapist and the resident of the service. The evaluation will be carried out at least 8 times over 21 days. If an abdominal massage is performed, an assessment of the abdominal condition by the scale will be necessary before and after each massage by the physiotherapist. Each assessment (by physio, nurse and resident) will be blinded and within a maximum time window of 30 minutes. The first evaluator clears the patient's abdomen (clothing and diaper removed) and then performs the assessment of the abdomen blindly. A description has been written so that each evaluator can use the ECAP scale under the same conditions and with well-detailed judgment criteria in order to have an evaluation that is as reliable as possible. The time taken to assess the premature baby's abdomen by the ECAP scale is less than 3 minutes. The evaluator fills out the ECAP assessment table, blindly. Within the next 30 minutes (the patient's abdominal condition is considered stable during this time), the second and third assessors have to do the same. These assessments are stored together with each patient's clinical data collection, and then analyzed by statisticians. ### Conditions Module **Conditions:** - Preterm Birth Complication - Digestive System Disease **Keywords:** - physiotherapy - abdominal massage ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** score between 0 and 20 **Measure:** Clinical Abdominal assessment scale for Preterm infant (ECAP scale) **Time Frame:** up to 18 months #### Secondary Outcomes **Description:** score on the Clinical Abdominal assessment scale for Preterm infants, between 0 and 20 (higher scores meaning worse outcome) **Measure:** Indication for abdominal massage on ECAP scale **Time Frame:** up to 18 months **Description:** term of birth population **Measure:** ECAP scale validity **Time Frame:** up to 18 months **Description:** variation of the score of Clinical Abdominal assessment scale for Preterm infants, between 0 and 20 (higher scores meaning worse outcome) **Measure:** impact of massage on ECAP scale **Time Frame:** up to 18 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * newborns, born prematurely (before 37 weeks of amenorrhea) * at least 3 days of life * hospitalized in the neonatal intensive care units * whose holders of parental authority are able to give free and informed consent to participate in this study Exclusion Criteria: * Newborns with congenital pathology such as malformation, genetic or chromosomal abnormality. * Newborns whose holders of parental authority are protected by law (under guardianship) or under the age of 18. * Rejection of participation by parents **Maximum Age:** 60 Days **Minimum Age:** 3 Days **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** Newborns born before 37 weeks of amenorrhea, hospitalized in the neonatal intensive care units ### Contacts Locations Module #### Locations **Location 1:** **City:** Clermont-ferrand **Country:** France **Facility:** CHU clermont-ferrand **Zip:** 63000 #### Overall Officials **Official 1:** **Affiliation:** mcolne@chu-clermontferrand.fr **Name:** Marie COLNÉ **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007752 - Term: Obstetric Labor, Premature - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M25869 - Name: Premature Birth - Relevance: HIGH - As Found: Preterm Birth - ID: M7255 - Name: Digestive System Diseases - Relevance: HIGH - As Found: Digestive System Diseases - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: HIGH - As Found: Digestive System Diseases - ID: M10772 - Name: Obstetric Labor, Premature - Relevance: LOW - As Found: Unknown - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000047928 - Term: Premature Birth ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04359979 **Brief Title:** Tamsulosin for Thyroid Lid Retraction **Official Title:** Treatment With Tamsulosin for Upper Eyelid Retraction Related to Thyroid Eye Disease. #### Organization Study ID Info **ID:** SHEBA-20-7022-OS-CTIL #### Organization **Class:** OTHER_GOV **Full Name:** Sheba Medical Center ### Status Module #### Completion Date **Date:** 2023-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-23 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-22 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-05-01 **Type:** ESTIMATED #### Start Date **Date:** 2020-05-01 **Type:** ACTUAL **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2020-04-24 **Type:** ACTUAL **Study First Submit Date:** 2020-04-21 **Study First Submit QC Date:** 2020-04-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Sheba Medical Center #### Responsible Party **Investigator Affiliation:** Sheba Medical Center **Investigator Full Name:** Dr. Oded Sagiv **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to examine the effect of using Tamsulosin for treatment of eyelid retraction as part of thyroid eye disease. The treatment will be offered to all thyroid patients suffering from eyelid retraction who are treated at the thyroid clinic in Sheba's Ophthalmology department. All patient will receive information about the drug Tamsulosin, the possible side effects, and the alternative treatment options for retraction. Patients recruited will take 0.4mg/day Tamsulosin for 3 months and will have follow-ups at 1 week, 1 month and 3 months to evaluate the retraction status. **Detailed Description:** Thyroid eye disease is a common autoimmune disorder caused by antibodies directed against receptors present in the thyroid cells and extra-ocular muscles and soft tissue of the orbit. The disorder is characterised by enlargement of the extra-ocular muscles, fatty and connective tissue volume. Upper lid retraction is the most common sign of the eye disease (present in up to 92%). The causes for retraction are not fully understood. It may be related to inflammation of the Levator muscle and the Muller muscle, or related to over sympathetic activity causing overstimulation of the Muller muscle. Upper lid retraction severity can range from very light to severe, with scleral show, eye dryness and even exposure keratopathy. Additionally it can have a very significant effect on the patient's appearance (a constant surprised look). Treatments for lid retraction include aggressive lubrication and tarsorrhaphy if needed (sewing the eyelids together). The Muller is a smooth muscle which elevates the upper eyelid and is sympathetically innervated (alpha receptor). The drug Tamsulosin which is a selective alpha1 receptor antagonist is commonly used today for benign prostatic hyperplasia (relaxing the prostate muscle). In this study we would like to test using Tamsulosin for treatment of lid retraction caused by thyroid eye disease. We hypothesise that the relaxation of the Muller muscle may have a beneficial effect on the retraction. ### Conditions Module **Conditions:** - Thyroid Eye Disease - Eyelid Diseases **Keywords:** - eyelid retraction - tamsulosin - alpha receptor antagonist ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** off label use of an approved drug for new indication ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients will receive 0.4mg/day of Tamsulosin tablet for 3 months **Intervention Names:** - Drug: Tamsulosin **Label:** tamsulosin treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - tamsulosin treatment **Description:** selective alpha1 receptor antagonist **Name:** Tamsulosin **Other Names:** - Omnic **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** measuring the upper margin to reflex distance (MRD1) **Measure:** eyelid retraction **Time Frame:** 1 week after starting tamsulosin treatment **Description:** measuring the upper margin to reflex distance (MRD1) **Measure:** eyelid retraction **Time Frame:** 1 month after starting tamsulosin treatment **Description:** measuring the upper margin to reflex distance (MRD1) **Measure:** eyelid retraction **Time Frame:** 3 months after starting tamsulosin treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Thyroid eye disease patients suffering from upper eyelid retraction in one or both eyes Exclusion Criteria: * pregnant/breastfeeding women * previous eyelid surgery/trauma **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** Oded.Sagiv@sheba.health.gov.il **Name:** Oded Sagiv, MD **Phone:** 97235302874 **Role:** CONTACT #### Locations **Location 1:** **City:** Tel Hashomer **Contacts:** ***Contact 1:*** - **Email:** oded.sagiv@sheba.health.gov.il - **Name:** Oded Sagiv, M.D. - **Role:** CONTACT **Country:** Israel **Facility:** Sheba Medical Center **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Sheba Medical Center **Name:** Oded Sagiv, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Yano S, Hirose M, Nakada T, Nakayama J, Matsuo K, Yamada M. Selective alpha 1A-adrenoceptor stimulation induces Mueller's smooth muscle contraction in an isolated canine upper eyelid preparation. Curr Eye Res. 2010 May;35(5):363-9. doi: 10.3109/02713680903518858. **PMID:** 20450248 **Citation:** Kikuchi-Utsumi K, Ishizaka M, Matsumura N, Nakaki T. Alpha(1A)-adrenergic control of piloerection and palpebral fissure width in rats. Auton Neurosci. 2013 Dec;179(1-2):148-50. doi: 10.1016/j.autneu.2013.04.011. Epub 2013 May 20. **PMID:** 23701912 **Citation:** Esmaeli-Gutstein B, Hewlett BR, Pashby RC, Oestreicher J, Harvey JT. Distribution of adrenergic receptor subtypes in the retractor muscles of the upper eyelid. Ophthalmic Plast Reconstr Surg. 1999 Mar;15(2):92-9. doi: 10.1097/00002341-199903000-00005. **PMID:** 10189635 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004700 - Term: Endocrine System Diseases - ID: D000015785 - Term: Eye Diseases, Hereditary - ID: D000006111 - Term: Graves Disease - ID: D000005094 - Term: Exophthalmos - ID: D000009916 - Term: Orbital Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000006042 - Term: Goiter - ID: D000006980 - Term: Hyperthyroidism - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M8271 - Name: Eye Diseases - Relevance: HIGH - As Found: Eye Disease - ID: M16718 - Name: Thyroid Diseases - Relevance: HIGH - As Found: Thyroid - ID: M26148 - Name: Graves Ophthalmopathy - Relevance: HIGH - As Found: Thyroid Eye Disease - ID: M8284 - Name: Eyelid Diseases - Relevance: HIGH - As Found: Eyelid Diseases - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M18339 - Name: Eye Diseases, Hereditary - Relevance: LOW - As Found: Unknown - ID: M9214 - Name: Graves Disease - Relevance: LOW - As Found: Unknown - ID: M8237 - Name: Exophthalmos - Relevance: LOW - As Found: Unknown - ID: M12845 - Name: Orbital Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M9147 - Name: Goiter - Relevance: LOW - As Found: Unknown - ID: M10031 - Name: Hyperthyroidism - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005128 - Term: Eye Diseases - ID: D000049970 - Term: Graves Ophthalmopathy - ID: D000005141 - Term: Eyelid Diseases - ID: D000013959 - Term: Thyroid Diseases ### Intervention Browse Module - Ancestors - ID: D000058668 - Term: Adrenergic alpha-1 Receptor Antagonists - ID: D000000317 - Term: Adrenergic alpha-Antagonists - ID: D000018674 - Term: Adrenergic Antagonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000064804 - Term: Urological Agents ### Intervention Browse Module - Browse Branches - Abbrev: Urol - Name: Urological Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1790 - Name: Tamsulosin - Relevance: HIGH - As Found: Headache - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M29194 - Name: Adrenergic alpha-1 Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M3669 - Name: Adrenergic alpha-Antagonists - Relevance: LOW - As Found: Unknown - ID: M20755 - Name: Adrenergic Antagonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077409 - Term: Tamsulosin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00856479 **Acronym:** Infuse **Brief Title:** A Randomized Controlled Cost Study of Infuse BMP 2 vs Iliac Crest Autograft for Non Union of Long Bone Fractures **Official Title:** A Randomized Controlled Cost Study of Infuse BMP 2 vs Iliac Crest Autograft for Non Union of Long Bone Fractures #### Organization Study ID Info **ID:** Infuse Study #### Organization **Class:** OTHER **Full Name:** Nova Scotia Health Authority #### Secondary ID Infos **ID:** COTS Grant ### Status Module #### Completion Date **Date:** 2013-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-14 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-08 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2010-03 **Type:** ESTIMATED #### Start Date **Date:** 2009-03 **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2009-03-05 **Type:** ESTIMATED **Study First Submit Date:** 2009-02-26 **Study First Submit QC Date:** 2009-03-04 **Why Stopped:** Study never started ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Canadian Orthopaedic Trauma Society #### Lead Sponsor **Class:** OTHER **Name:** Ross Leighton #### Responsible Party **Investigator Affiliation:** Nova Scotia Health Authority **Investigator Full Name:** Ross Leighton **Investigator Title:** Orthopedic Surgeon **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** We are inviting individuals such as yourself, who have diaphyseal fracture (broken bone) with a non union to participate in this research study. A non-union is a lack of bone healing (bone growth where the break in the bone occurred) after 3 months after the operation. The diaphyseal is an area of a specific bone (usually near the middle) where the fracture occurred. The bones we are interested in are the clavicle (collar bone), tibia (lower leg), femur (upper leg), humerus (upper arm) and forearm (lower arm). Treatment goals for these types of fractures are to minimize later surgeries, to assist the healing process, and to decrease the time to healing. The ability of a patient with non-union (lack of bone healing after 3 months post operation) to return to the work force and to normal activities more quickly not only has a good financial impact on society (community), but also improves over-all physical and mental well-being of the patients. "Infuse" is a synthetic bone morphogenic protein which means it has the ability to help your bone to form and heal if inserted in the fracture site. "Infuse" may be the first commercially available product approved by Health Canada to accelerate the healing of long bone non-unions requiring surgical intervention. Although the safety and efficacy of Infuse has been demonstrated through numerous pre-clinical studies, further human clinical trial is needed to evaluate the safety and the power to produce effects of this product particularly with respect to non unions of long bones. The purpose of this study is to evaluate the safety and the power to produce effects of Infuse implanted during treatment of long bone non unions to reduce later surgeries required to augment the healing process and to accelerate the time to healing. Given this, the orthopaedic community has planned this study in order to scientifically establish the most effective treatment method to restore function after this type of injury. **Detailed Description:** We propose a multi-centre Canadian randomized Study wherein 80 patients are randomized (put in groups by no standard pattern ie. flipping a coin) to receive both autograft (sample of your own bone: iliac crest) and allograft (bone chips from bone bank) or "infuse" (synthetic bone morphogenic protein) and allograft using locked plates. Locked plates are surgical plates placed on the fracture in which the screws lock into the plate when they have been completely screwed into the bone through holes on the plate. Our objective is to assess the total cost of the patients treated in both study group and the benefits of the Infuse by comparing the new bone formation in the fracture site. We will monitor critical aspects of operative care and rehabilitation at regular intervals, up to 2 year after surgery. We will independently monitor revision surgery (surgeries to repair a previous surgery) rates. We will also assess patients for functional health and quality of life outcomes. ### Conditions Module **Conditions:** - Non Union Diaphyseal Fractures **Keywords:** - Infuse - cost analysis - Non union diaphyseal fracture - The efficacy of Infuse BMP 2 in Non union diaphyseal fractures. Also the cost analysis with the amount of time spent in hospital post op. ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patient will receive BMP 2 with allograft **Intervention Names:** - Device: Infuse Bone Morphogenic Protein (BMP) 2 **Label:** 1 Infuse **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Autograft from Patients Iliac Crest and allograft **Intervention Names:** - Procedure: iliac crest autograft **Label:** 2 Iliac crest autograft **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 Infuse **Description:** "Infuse" is a synthetic bone morphogenic protein which means it has the ability to help your bone to form and heal if inserted in the fracture site. "Infuse" may be the first commercially available product approved by Health Canada to accelerate the healing of long bone non-unions requiring surgical intervention. **Name:** Infuse Bone Morphogenic Protein (BMP) 2 **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - 2 Iliac crest autograft **Description:** A piece of the patients iliac crest bone is take and mixed with bone from a bone bank to supplement the bone loss in the fracture **Name:** iliac crest autograft **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** cost analysis based on length of hospital stay, allograft, blood products and costs associated with complications and/ or re-admission. **Time Frame:** 2 years #### Secondary Outcomes **Measure:** Secondary efficacy end points will be the radiographic assessment of healing (RUST scale), the clinical assessment of weight-¬bearing status at 6 months post treatment, and the incidence of additional surgical/medical interventions to promote healing. **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Patients must meet all of the following criteria to be eligible for entry into the study: a) Patients must require open surgical treatment of non-union of a diaphyseal fracture of the tibia, humerus, femur, radius or ulna sustained secondary to trauma. c) Patients must be candidates for surgical treatment with an intramedullary nail or locked or unlocked plate. d) Patients must have a fracture of the diaphysis as defined for that specific bone. e) Patients must show radiographic evidence of skeletal maturity (closed epiphyseal plates). Exclusion Criteria: Patients with any of the following criteria, are not eligible for entry into the study: 1. Patients requiring mechanical fixation other than Intramedullary nailing or plating (i.e. no external fixation) 2. Patients with fractures that fall outside the diaphysis defined for the specific bone in question, i.e. no metaphyseal fractures. 3. Patients with segmental circumferential bone loss \>4cm. 4. Patients whose fractures are the result of a tumour 5. Infection per se, does not result in exclusion but it must be treated and the soft tissue envelope closed prior to randomization 6. Patients with known metabolic bone disease (other than osteoporosis) which would negatively impact on the bone healing process. 7. Patients with known sensitivity to collagen. 8. Patients who are pregnant or breastfeeding at the time of study enrolment. 9. Patients currently being treated with radiation, chemotherapy, immunosuppression, or steroid therapy. 10. Patients receiving any other investigational drug or treatment. 11. Patients who have other injuries or conditions such as they are unable to communicate or consent m)Patients with known breast or prostate cancer f) Patients must be able and willing to provide informed consent, to complete study assessments, and to be followed for the period of the study. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Halifax **Country:** Canada **Facility:** Halifax Infirmary **State:** Nova Scotia **Zip:** B3h 1V7 #### Overall Officials **Official 1:** **Affiliation:** CDHA **Name:** Ross K Leighton, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: HIGH - As Found: Fracture - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000050723 - Term: Fractures, Bone ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06412679 **Acronym:** RESETTLE-IDPs **Brief Title:** RESETTLE-IDPs: Life-Skills Education and Psychosocial Resilience Building for Displaced Nigerians **Official Title:** Rebuilding Emotional Stability and Strength Through Therapeutic and Life-Skills Education for Internally Displaced Persons in Nigeria (RESETTLE-IDPs): A Hybrid Type II Effectiveness-implementation Study #### Organization Study ID Info **ID:** 2024-7085 #### Organization **Class:** OTHER **Full Name:** Dalhousie University #### Secondary ID Infos **Domain:** CIHR **ID:** PAA - 192178 **Type:** OTHER_GRANT **Domain:** Grand Challenges Canada **ID:** R-HGC-POC-2408-67370 **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2025-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-16 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-14 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-07 **Type:** ESTIMATED #### Start Date **Date:** 2024-08 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-14 **Type:** ACTUAL **Study First Submit Date:** 2024-05-09 **Study First Submit QC Date:** 2024-05-09 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** University of Maiduguri Teaching Hospital **Class:** UNKNOWN **Name:** Brooks Insights #### Lead Sponsor **Class:** OTHER **Name:** Dalhousie University #### Responsible Party **Investigator Affiliation:** Dalhousie University **Investigator Full Name:** Ejemai Eboreime **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The RESETTLE-IDPs study aims to address the urgent mental health needs of internally displaced youth and women in Nigeria, who face high rates of depression, anxiety, and post-traumatic stress due to exposure to conflict, violence, and loss. Despite the immense needs, there is a severe lack of culturally appropriate, evidence-based interventions to support the resilience and well-being of these vulnerable populations. To fill this gap, the study will evaluate the effectiveness and implementation of a novel life skills education (LSE) program delivered through two innovative approaches: in-person peer support groups and WhatsApp-based virtual support groups. The LSE curriculum, developed through extensive community engagement, covers topics such as stress management, communication, problem-solving, health, safety, and advocacy, all tailored to the unique challenges of displacement. In the in-person arm, trained IDP peers and local providers will facilitate weekly group sessions over 12 weeks, providing a safe space for participants to learn, practice, and apply new skills while building social connections and support networks. In the WhatsApp arm, participants will receive weekly messages with educational content, reflection prompts, and exercises, moderated by trained facilitators to foster dialogue and peer support. By comparing these two delivery methods, the study aims to identify the most feasible, acceptable, and effective strategies for rolling out psychosocial support interventions in humanitarian settings, particularly those with limited resources and access. The study will also assess the interventions' impact on key mental health outcomes, including depression, anxiety, PTSD, and well-being, as well as life skills, functioning, and implementation metrics such as reach, adoption, and sustainability. Ultimately, the RESETTLE-IDPs study seeks to generate actionable evidence to inform the development and scale-up of culturally responsive, community-driven interventions that can promote the mental health and resilience of conflict-affected populations in Nigeria and beyond. By empowering IDP youth and women with the knowledge, skills, and support to navigate the challenges of displacement, the study aims to contribute to a brighter, more hopeful future for these resilient communities **Detailed Description:** The RESETTLE-IDPs study is a cluster-randomized type II effectiveness-implementation hybrid trial that aims to evaluate the effectiveness and implementation of a life skills education (LSE) intervention delivered through two innovative approaches - in-person peer support groups and WhatsApp-based virtual support groups - to improve the mental health and well-being of internally displaced persons in Nigeria. Background and Rationale: Nigeria is facing a severe humanitarian crisis, with over 2.7 million people internally displaced due to armed conflict, communal violence, and natural disasters. Internally displaced persons (IDPs) in Nigeria, particularly youth and women, are at high risk of mental health problems such as depression, anxiety, and post-traumatic stress disorder (PTSD) due to exposure to trauma, loss, and ongoing stressors. Despite the immense needs, there is a severe lack of culturally appropriate, evidence-based interventions to support the mental health and resilience of IDP populations in Nigeria and other low-resource humanitarian settings. Life skills education (LSE) is a promising approach to promoting mental health and well-being among conflict-affected populations. LSE programs aim to equip individuals with the knowledge, attitudes, and skills needed to navigate challenges, cope with stress, and make healthy decisions. Previous studies have shown that LSE interventions can improve mental health outcomes, social-emotional learning, and positive youth development in various contexts. However, there is limited evidence on the effectiveness and implementation of LSE programs specifically tailored for IDP youth and women in Nigeria, and how different delivery methods (e.g., in-person vs. mobile-based) may impact their reach, acceptability, and sustainability. Study Objectives: The primary objective of the RESETTLE-IDPs study is to evaluate the effectiveness of a 12-week LSE intervention, delivered through either in-person peer support groups or WhatsApp-based virtual support groups, on mental health outcomes (depression, anxiety, PTSD, and well-being) among IDP youth and women in Nigeria, compared to a wait-list control group. Secondary objectives include: 1. To assess the impact of the LSE intervention on life skills acquisition, daily functioning, and social support among IDP youth and women. 2. To compare the feasibility, acceptability, fidelity, and cost-effectiveness of in-person vs. WhatsApp-based delivery methods for the LSE intervention. 3. To explore the contextual factors, implementation processes, and mechanisms of change that influence the effectiveness and sustainability of the LSE intervention in IDP settings. 4. To engage stakeholders (IDP communities, health workers, humanitarian organizations, policymakers) in the design, implementation, and evaluation of the LSE intervention to promote its cultural relevance, ownership, and scalability. Methods: The study will use a three-arm cluster-randomized controlled trial design, with IDP camps in Nigeria randomly allocated to one of two groups: (1) in-person LSE peer support groups, (2) WhatsApp-based LSE virtual support groups. The target population includes IDPs youth aged 13 years and above residing in selected camps in Borno State, the epicenter of the Boko Haram insurgency and displacement crisis in Nigeria. The intervention will consist of a culturally adapted LSE curriculum covering topics such as stress management, communication skills, problem-solving, health and hygiene, safety and protection, gender norms, and community mobilization. The curriculum will be developed through a participatory process involving IDP youth and women, community leaders, health workers, and education specialists, drawing on existing evidence-based resources and guidelines (e.g. UNICEF LSE Toolkit). In the in-person arm, trained IDP peers and local providers will facilitate weekly gender- and age-segregated support groups of 10-12 participants over a 12-week period. The groups will provide a safe space for participants to learn and practice life skills, share experiences, and provide mutual support. Sessions will use interactive, experiential learning methods such as role-plays, discussions, and group projects. In the WhatsApp arm, participants will be enrolled in moderated virtual support groups that deliver the LSE curriculum through weekly conversations, including psychoeducational content, reflection prompts, skill-building exercises, and peer discussion topics. Trained IDP facilitators will moderate the groups to ensure safe and supportive interactions, provide feedback, and encourage skill application. The study will enroll a total of 500 participants (250 per arm) across 20 IDP camps, with an estimated 25 participants per camp. Participants will be recruited through community-based mobilization strategies, with support from camp leaders, health workers, and NGO partners. Data will be collected at baseline, 3 months, 6 months, and 12 months using a combination of quantitative and qualitative methods. Quantitative data will include validated mental health scales, as well as locally adapted measures of life skills, functioning, and social support. Qualitative data will include in-depth interviews and focus group discussions with participants, facilitators, and stakeholders to explore experiences, perceptions, and contextual factors influencing the intervention. Data analysis will use an intent-to-treat approach, with mixed-effects regression models to assess intervention effects on primary and secondary outcomes, accounting for clustering at the camp level. Qualitative data will be analyzed thematically to identify barriers, facilitators, and mechanisms of change. Implementation outcomes (e.g., reach, fidelity, acceptability) will be assessed using process evaluation frameworks (e.g., RE-AIM). Expected Results and Impact: The RESETTLE-IDPs study aims to generate rigorous evidence on the effectiveness and implementation of a culturally adapted LSE intervention for improving the mental health and well-being of IDP youth and women in Nigeria. The study findings will have important implications for the design, delivery, and scale-up of psychosocial support interventions in humanitarian settings, particularly those affected by conflict and displacement. By comparing in-person and WhatsApp-based delivery methods, the study will provide valuable insights into the relative advantages, challenges, and effectiveness of different approaches to reaching and engaging IDP populations. The use of implementation science frameworks and participatory research methods will ensure that the intervention is not only effective but also feasible, acceptable, and sustainable in real-world contexts. The study will also contribute to capacity-building and empowerment of IDP communities by training and engaging youth and women as peer facilitators, researchers, and advocates. The participatory approach aims to foster local ownership, leadership, and sustainability of the intervention beyond the research period. Ultimately, the RESETTLE-IDPs study has the potential to inform policy, practice, and funding priorities for mental health and psychosocial support in humanitarian settings, both in Nigeria and globally. By advancing the evidence base on culturally relevant, community-based interventions, the study can contribute to reducing the global burden of mental health disorders and promoting the resilience and well-being of conflict-affected populations. ### Conditions Module **Conditions:** - Mental Health - Psychosocial Functioning - Implementation Science - Global Health - Conflict **Keywords:** - Conflict - Forced Displacement - Internally displaced persons - Mental health - Psychosocial support - Life skills education - Mobile health - Digital health - Humanitarian emergencies - Global mental health ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Type II Hybrid Effectiveness-Implementation Design ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 500 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive a culturally-adapted LSE intervention delivered through weekly in-person peer support group sessions for 12 weeks. The LSE curriculum covers topics such as stress management, communication skills, problem-solving, emotion regulation, health and hygiene, social skills, gender norms and safety, education and livelihoods, and community mobilization. Each peer support group will consist of 10-12 participants, separated by gender and age bands (12-17 and 18-24 for youth, 18+ for women), and will meet weekly for approximately 2 hours in a private, safe space within the IDP camp. Sessions will be co-facilitated by a trained IDP peer leader and a local mental health provider, following a structured format with interactive activities, discussions, and skill practice. **Intervention Names:** - Behavioral: Life Skills Education **Label:** In-Person Life Skills Education (LSE) Peer Support Groups **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Participants will receive the same culturally-adapted LSE curriculum as those in the In-person arm, but delivered through WhatsApp for 12 weeks. Participants will be added to a moderated WhatsApp group chat with other IDP youth or women in their camp, where they will receive three LSE-related messages per week. These messages will include brief psychoeducational content, practice exercises, reflection prompts, and reminders to engage with the virtual support group. The WhatsApp group will provide a platform for participants to discuss the LSE topics, share experiences and coping strategies, and provide emotional support to one another, with trained IDP peer facilitators moderating the chats to ensure a safe and supportive environment. Participants will also receive regular push notifications with motivational messages, links to further resources, and reminders to practice the LSE skills. **Intervention Names:** - Behavioral: Life Skills Education **Label:** WhatsApp-Enabled LSE Virtual Peer Support Groups **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - In-Person Life Skills Education (LSE) Peer Support Groups - WhatsApp-Enabled LSE Virtual Peer Support Groups **Description:** The RESETTLE-IDPs study compares two innovative delivery approaches for a culturally-adapted life skills education (LSE) intervention aimed at improving the mental health and well-being of internally displaced persons in Nigeria. The interventions are distinguished by their mode of delivery (in-person vs. WhatsApp-based), their focus on peer support and skill-building, and their tailoring to the specific needs and challenges of IDP populations. **Name:** Life Skills Education **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Metric/Method of Measurement: PTSD Checklist for DSM-5 (PCL-5) The PCL-5 is a 20-item self-report measure that assesses the presence and severity of PTSD symptoms based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. Participants rate how much they have been bothered by each symptom in the past month on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The total score ranges from 0 to 80, with higher scores indicating greater severity of PTSD symptoms. A score of 31-33 or higher suggests probable PTSD diagnosis. **Measure:** Change in Post-Traumatic Stress Disorder (PTSD) symptoms **Time Frame:** Baseline, 3 months, 6 months, and 12 months #### Secondary Outcomes **Description:** Metric/Method of Measurement: Patient Health Questionnaire-9 (PHQ-9) The PHQ-9 is a 9-item self-report measure that assesses the presence and severity of depressive symptoms based on the DSM-5 criteria. Participants rate how often they have been bothered by each symptom over the past 2 weeks on a 4-point scale ranging from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27, with higher scores indicating greater severity of depressive symptoms. Cut-off scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively. **Measure:** Change in depressive symptoms **Time Frame:** Baseline, 3 months, 6 months, and 12 months **Description:** Metric/Method of Measurement: Generalized Anxiety Disorder-7 (GAD-7) The GAD-7 is a 7-item self-report measure that assesses the presence and severity of anxiety symptoms. Participants rate how often they have been bothered by each symptom over the past 2 weeks on a 4-point scale ranging from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 21, with higher scores indicating greater severity of anxiety symptoms. Cut-off scores of 5, 10, and 15 represent mild, moderate, and severe anxiety, respectively. **Measure:** Change in anxiety symptoms **Time Frame:** Baseline, 3 months, 6 months, and 12 months **Description:** Metric/Method of Measurement: A Life Skills Assessment Tool (LSAT) The LSAT is a locally developed measure that assesses participants' knowledge, attitudes, and behaviors related to the key life skills covered in the LSE curriculum (e.g., stress management, communication, problem-solving, health and hygiene). The scale includes a mix of multiple-choice and Likert-type items, with higher scores indicating greater life skills competency. The exact number of items and scoring system will be determined through formative research and pilot testing with the target population. **Measure:** Change in life skills **Time Frame:** Baseline, 3 months, 6 months, and 12 months **Description:** Metric/Method of Measurement: World Health Organization-Five Well-Being Index (WHO-5) The WHO-5 is a 5-item self-report measure that assesses subjective psychological well-being over the past 2 weeks. Participants rate each item on a 6-point scale ranging from 0 (at no time) to 5 (all of the time). The total score ranges from 0 to 25, which is then multiplied by 4 to yield a percentage score ranging from 0 to 100. A score below 50 suggests poor well-being and a score below 28 indicates likely depression. **Measure:** Change in well-being **Time Frame:** Baseline, 3 months, 6 months, and 12 months **Description:** Metric/Method of Measurement: Intervention Appropriateness Measure (IAM) The IAM is a 4-item self-report measure that assesses the perceived appropriateness of an intervention. Participants rate each item on a 5-point scale ranging from 1 (completely disagree) to 5 (completely agree). The total score ranges from 4 to 20, with higher scores indicating greater appropriateness. **Measure:** Change in perceived appropriateness of the intervention **Time Frame:** Baseline, 3 months **Description:** Metric/Method of Measurement: Acceptability of Intervention Measure (AIM) The AIM is a 4-item self-report measure that assesses the perceived acceptability of an intervention. Participants rate each item on a 5-point scale ranging from 1 (completely disagree) to 5 (completely agree). The total score ranges from 4 to 20, with higher scores indicating greater acceptability. **Measure:** Change in acceptability of the intervention **Time Frame:** Baseline, 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 13 years and above * Ownership of smartphone * Internally displaced for at least 6 months. * Residing in select IDP camps in Abuja and Borno State, Nigeria * Fluency in English and/or Hausa languages * Willing and able to provide informed consent. Exclusion Criteria: * Active suicidal ideation or attempts (i.e having thoughts, plans, or intent to end one\&#39;s life within the past month) * Active psychosis * Cognitive impairment precluding informed consent or survey completion. * Not owning as smartphone **Healthy Volunteers:** True **Minimum Age:** 13 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** ejemai.eboreime@dal.ca **Name:** Ejemai A Eboreime, MBBS, PhD **Phone:** 902-473-2479 **Role:** CONTACT **Contact 2:** **Email:** chisom.obijeff@brooksinsights.org **Name:** Chisom Obi-Jeff **Phone:** +2348038878844 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Dalhousie University **Name:** Ejemai A Eboreime, MBBS, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Dalhousie University **Name:** Vincent Agyapong, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Dalhousie University **Name:** Rita Orji, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 4:** **Affiliation:** University of Ottawa **Name:** Sanni Yaya, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Data Sharing Statement We will share de-identified IPD underlying the published results of the RESETTLE-IDPs study, including the study protocol, statistical analysis plan, and analytic code. IPD will be made available upon reasonable request and after approval by the study's steering committee, subject to a data sharing agreement. Access Criteria and Procedure Researchers interested in accessing the IPD should submit a formal request to the study's principal investigator, specifying the purpose, scope, and timeline of the proposed analyses. Requests will be reviewed by the steering committee based on the scientific merit, feasibility, and alignment with the study's objectives and participants' informed consent. **Description:** We will share de-identified IPD underlying the published results of the RESETTLE-IDPs study, including the study protocol, statistical analysis plan, and analytic code. IPD will be made available upon reasonable request and after approval by the study's steering committee, subject to a data sharing agreement **Info Types:** - STUDY_PROTOCOL - SAP - ICF - ANALYTIC_CODE **IPD Sharing:** YES **URL:** ftp://NA ### References Module #### References **Citation:** Kaiser BN, Ticao C, Boglosa J, Minto J, Chikwiramadara C, Tucker M, Kohrt BA. Mental health and psychosocial support needs among people displaced by Boko Haram in Nigeria. Glob Public Health. 2020 Mar;15(3):358-371. doi: 10.1080/17441692.2019.1665082. Epub 2019 Sep 19. **PMID:** 31535595 **Citation:** Ugbe UM, Esu EB, Efut JA, Bisongedam MM, Awa TM, Ekpo OI. Sociodemographic correlates and associated factors of depression and anxiety among internally displaced adults in Ogoja, Nigeria. Gen Psychiatr. 2022 Apr 28;35(2):e100749. doi: 10.1136/gpsych-2022-100749. eCollection 2022. **PMID:** 35572773 **Citation:** Wei Y, Hayden JA, Kutcher S, Zygmunt A, McGrath P. The effectiveness of school mental health literacy programs to address knowledge, attitudes and help seeking among youth. Early Interv Psychiatry. 2013 May;7(2):109-21. doi: 10.1111/eip.12010. Epub 2013 Jan 24. **PMID:** 23343220 **Citation:** Taubner S, Ioannou Y, Saliba A, Sales CMD, Volkert J, Protic S, Adler A, Barkauskiene R, Conejo-Ceron S, Di Giacomo D, Mestre JM, Moreno-Peral P, Vieira FM, Mota CP, Henriques MIRS, Rossberg JI, Perdih TS, Schmidt SJ, Zettl M, Ulberg R, Heinonen E. Mediators of outcome in adolescent psychotherapy and their implications for theories and mechanisms of change: a systematic review. Eur Child Adolesc Psychiatry. 2023 Mar 15. doi: 10.1007/s00787-023-02186-9. Online ahead of print. **PMID:** 36918434 **Citation:** Sahebalzamani M, Farahani H, Feizi F. Efficacy of life skills training on general health in students. Iran J Nurs Midwifery Res. 2012 Nov;17(7):553-5. **PMID:** 23922605 **Citation:** Singla DR, Waqas A, Hamdani SU, Suleman N, Zafar SW, Zill-E-Huma, Saeed K, Servili C, Rahman A. Implementation and effectiveness of adolescent life skills programs in low- and middle-income countries: A critical review and meta-analysis. Behav Res Ther. 2020 Jul;130:103402. doi: 10.1016/j.brat.2019.04.010. Epub 2019 Apr 26. **PMID:** 31146889 **Citation:** Maghsoudi J, Sabour NH, Yazdani M, Mehrabi T. The effect of acquiring life skills through humor on social adjustment rate of the female students. Iran J Nurs Midwifery Res. 2010 Fall;15(4):195-201. **PMID:** 22049280 **Citation:** Magnani R, Macintyre K, Karim AM, Brown L, Hutchinson P, Kaufman C, Rutenburg N, Hallman K, May J, Dallimore A; Transitions Study Team. The impact of life skills education on adolescent sexual risk behaviors in KwaZulu-Natal, South Africa. J Adolesc Health. 2005 Apr;36(4):289-304. doi: 10.1016/j.jadohealth.2004.02.025. **PMID:** 15780784 **Citation:** undefined ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7796 - Name: Emergencies - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03444779 **Acronym:** TUBERIMPACT **Brief Title:** Comparative Evaluation of Minimally Invasive "Tibial Tuberoplasty" Surgical Technique Versus Conventional Open Surgery for Tibial Plateau Fractures **Official Title:** Comparative Evaluation of Minimally Invasive "Tibial Tuberoplasty" Surgical Technique Versus Conventional Open Surgery for Tibial Plateau Fractures (TUBERIMPACT Study) #### Organization Study ID Info **ID:** 2018-A01027-48 #### Organization **Class:** OTHER **Full Name:** Poitiers University Hospital ### Status Module #### Completion Date **Date:** 2024-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-01-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-12 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2022-10-26 **Type:** ACTUAL #### Start Date **Date:** 2018-10-26 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2018-02-23 **Type:** ACTUAL **Study First Submit Date:** 2018-02-02 **Study First Submit QC Date:** 2018-02-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Poitiers University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** PMSI (French Medico-Administrative Database) data shows more than 10000 proximal tibial fractures diagnosed in 2014 and 4055 lateral tibial plateau fractures operated in 2013 in France. 50% of these surgical fractures is related to the lateral condyle and causes split/depression (Schatzker 2) or pure depression (Schatzker 3). This high rate results from the recent democratization of high-risk sports, as well as an aging population with increased risks of falling. Aside from the resulting reduced physical activity, the social and professional impact of these fractures is undeniable and represents significant costs for our health care system. A recently published prospective case series reports 28 job losses out of 41 patients treated. The clinical outcome of these patients depends mainly on the primary stability provided by the surgical treatment, after the greatest anatomical reduction possible. Indeed, Giannoudis and al. have demonstrated that under simple X-rays, the smaller the detected step-off, the better the outcome.The aim is to allow for recovery of good joint mobility to promote rapid resumption of activity and to limit the onset of early osteoarthritis. The classical technique used for reduction and osteosynthesis of tibial plateau fractures (open surgical technique using a bone tamp) has several pitfalls : devascularization of the bone and skin, risks of infection and functional rehabilitation difficulties with delayed recovery of weight bearing. Moreover, this technique does not allow for the simultaneous diagnosis and treatment of other possible lesions, such as meniscal injuries in particular. Since 2011, Poitiers University Hospital is offering to its patients a new minimally invasive technique for the reduction and stabilization of tibial plateau fractures, baptized "Tibial Tuberoplasty". The concept derives from the divergent use of vertebral kyphoplasty, initially dedicated for spinal injuries and transposed here to the tibial plateau. This technique involves expansion of the tibial plateau through inflation of a kyphoplasty balloon, filling of the created cavity with cement (PMMA, calcium phosphate) and percutaneous screw fixation. Orthopaedic surgeons of Poitiers University Hospital performed the first tibial tuberoplasties through a feasibility study on 36 cadaveric subjects and then transposed the technique to human. Surgeons identified major advantages such as minimal skin damage, possible treatment of posterior and multi-fragmented compressions (lifting in a single block by the balloon), reinforcement of the stability of the assembly using cement, possible use of combined arthroscopy (for concomitant meniscal injuries treatment). This technique allows for optimization of the fracture reduction by elevating the posterior fragments with the inflatable bone tamp through an anterior approach. The reduction is made possible thanks to the specificity of the inflatable bone tamp which inflates and reduces the area of least resistance. The aim of this innovative technique is focused on the anatomical reduction in order to restore the convexity of the tibial plateau which is similar to the balloon convexity. The results from the first 40 patients operated since 2011 are promising and show a proportion of 70% presenting less than 5 mm step-off reduction. A larger scale multicenter randomized controlled trial is now requested to further demonstrate the superiority of the "Tibial Tuberoplasty" to the standard treatment. The coordinator investigator designed this study to evaluate the quality of tibial fracture reduction offered by percutaneous "Tibial Tuberoplasty" versus conventional open surgery for tibial plateau fracture but also its impact on clinical outcome. ### Conditions Module **Conditions:** - Schatzker Type 2 or 3 Tibial Plateau Fracture **Keywords:** - tibial plateau fracture - minimally invasive surgery - ballon reduction ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Masking Description:** Patient blinded until D2 visit. **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 140 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patients will be treated with an open technique: cutaneous incision with submeniscal arthrotomy under guidance of a fluoroscope. The reduction will be performed using a spatula, a bone tamp or open reduction internal fixation. The osteosynthesis and filling of the cavity will be performed by the same surgical access. **Intervention Names:** - Device: Open technique **Label:** Control group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** The patients will be treated with the "Tibial Tuberoplasty" technique under fluoroscopic guidance with or without arthroscopy. The reduction will be performed by an anterior approach using a kyphoplasty balloon. The combined osteosynthesis including cannulated screws and cementoplasty will both be performed by a percutaneous technique. **Intervention Names:** - Device: Tibial Tuberoplasty **Label:** Experimental group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental group **Description:** Kyphoplasty ballon **Name:** Tibial Tuberoplasty **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control group **Description:** Cutaneous incision with submeniscal arthrotomy under guidance of a fluoroscope. **Name:** Open technique **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Compare step-off anatomical reduction of tibial plateau fracture by "Tibial Tuberoplasty" versus conventional open surgery using CT-scan **Measure:** Post-operative radiological step-off reduction blindly measured by high resolution CT-scan **Time Frame:** Day 2 #### Secondary Outcomes **Description:** Knee range of motion **Measure:** Knee range of motion (degrees) **Time Frame:** Day 21, Day 45, Month 3, Month 6, Month 12 and Month 24 **Description:** The NPRS is an 11-point scale from 0-10 ("0" = no pain and "10" = the most intense pain imaginable). Patients verbally select a value that is most in line with the intensity of pain that they have experienced in the last 24 hours. **Measure:** Numeric Pain Rating Scale **Time Frame:** Inclusion, Day 2, Day 21, Day 45, Month 3, Month 6, Month 12 and Month 24 **Description:** The KOOS questionnaire is a functional score validated in the French language and one of the only validated in knee trauma. The Knee injury and Osteoarthritis Outcome Score (KOOS) was developed as an extension of the WOMAC Osteoarthritis Index with the purpose of evaluating short-term and long-term symptoms and function in subjects with knee injury and osteoarthritis. The KOOS holds five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS has been validated for several orthopaedic interventions such as anterior cruciate ligament reconstruction, meniscectomy and total knee replacement. **Measure:** Knee injury and Osteoarthritis Outcome Score **Time Frame:** Inclusion, Day 21, Day 45, Month 3, Month 6, Month 12 and Month 24 **Description:** The EQ-5D-5L is a standardized instrument used to measure health-related quality of life (HRQoL) which comprises a descriptive system and a visual analogue scale. The descriptive system is composed of 5 questions assessing mobility, self-care, usual activities, pain/discomfort and anxiety/depression with 5 possible responses for each item: 1- no problems, 2- slight problems, 3- moderate problems, 4- severe problems and 5- extreme problems). A global index with a maximum score of 1 is calculated from the responses to these 5 dimensions by means of normograms. The maximum score of 1 indicates the best possible quality of life. The visual analogue scale ranging from 0 to 100 also allows the patient to rate his/her perceived quality of life, where 100 indicates the best possible quality of life. **Measure:** Score on Euro Quality of Life-5 Dimension Health questionnaire **Time Frame:** Inclusion, Day 45, Month 3, Month 6, Month 12 and Month 24 **Description:** Adverse events **Measure:** Description of Adverse events **Time Frame:** from Inclusion to Month 24 (End Of Study) **Description:** Time to partial and full weight-bearing **Measure:** Time to partial and full weight-bearing **Time Frame:** from Day 0 (surgery) to Month 24 (End Of Study) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age ≥ 18 years old. 2. Patients with a Schatzker type 2 or 3 tibial plateau fracture (compression with or without split) demonstrated on CT-scan and located in the lateral or medial condyle of tibia. 3. Patients with fractures caused by trauma. 4. Patients with fractures 10 days old maximum. 5. Understand and accept the constraints of the study. 6. Be a beneficiary or affiliated member of a Health Insurance plan. 7. Give written consent for the study after having received clear information. Exclusion Criteria: 1. Age \< 18 years old. 2. Patients with fractures resulting from osteolysis. 3. Patients with open fractures. 4. Patients with fractures more than 10 days old. 5. Patients with concomitant fracture(s) or condition(s) during the trauma reducing the range of motion. 6. Patients unable to walk before the injury. 7. History of sepsis in the injured knee. 8. Contraindications to anesthesia, contrast agent, medical devices or cement. 9. History of hypersensitivity reactions to contrast media, bone filler or metal. 10. Patients with a degenerative joint disease (polyarthritis, etc.). 11. Absence of signature of the informed consent form. 12. Patients not covered by French national health insurance. 13. Subjects requiring closer protection, i.e. minors, pregnant women, nursing mothers, subjects deprived of their freedom by a court or administrative decision, subjects admitted to a health or social welfare establishment, major subjects under legal protection, and finally patients in an emergency setting. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Amiens **Country:** France **Facility:** CHU d'Amiens **Location 2:** **City:** Angers **Country:** France **Facility:** CHU Angers **Location 3:** **City:** Boulogne-Billancourt **Country:** France **Facility:** AP-HP / Hopital Ambroise Paré **Location 4:** **City:** Brest **Country:** France **Facility:** CHU de Brest **Location 5:** **City:** Dijon **Country:** France **Facility:** CHU Dijon **Location 6:** **City:** Nantes **Country:** France **Facility:** CHU de Nantes **Location 7:** **City:** Poitiers **Country:** France **Facility:** CHU de Poitiers **Location 8:** **City:** Rennes **Country:** France **Facility:** CHU de Rennes **Location 9:** **City:** Rouen **Country:** France **Facility:** CHU Rouen **Location 10:** **City:** Tours **Country:** France **Facility:** CHRU Tours **Location 11:** **City:** Versailles **Country:** France **Facility:** CH Versailles **Location 12:** **City:** Fort de France **Country:** Martinique **Facility:** CHU de Martinique #### Overall Officials **Official 1:** **Affiliation:** Poitiers Hospital University **Name:** Tanguy VENDEUVRE, Dr **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Vendeuvre T, Monlezun O, Brandet C, Ingrand P, Durand-Zaleski I, Gayet LE, Germaneau A, Khiami F, Roulaud M, Herpe G, Rigoard P. Comparative evaluation of minimally invasive 'tibial tuberoplasty' surgical technique versus conventional open surgery for Schatzker II-III tibial plateau fractures: design of a multicentre, randomised, controlled and blinded trial (TUBERIMPACT study). BMJ Open. 2019 Sep 3;9(8):e026962. doi: 10.1136/bmjopen-2018-026962. **PMID:** 31481365 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries - ID: D000092443 - Term: Knee Fractures - ID: D000013978 - Term: Tibial Fractures - ID: D000007718 - Term: Knee Injuries - ID: D000007869 - Term: Leg Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: HIGH - As Found: Fracture - ID: M2925 - Name: Tibial Plateau Fractures - Relevance: HIGH - As Found: Tibial Plateau Fractures - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M2923 - Name: Knee Fractures - Relevance: LOW - As Found: Unknown - ID: M16737 - Name: Tibial Fractures - Relevance: LOW - As Found: Unknown - ID: M10738 - Name: Knee Injuries - Relevance: LOW - As Found: Unknown - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000050723 - Term: Fractures, Bone - ID: D000092463 - Term: Tibial Plateau Fractures ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01895179 **Acronym:** TIMED EATING **Brief Title:** Comparison of Time-Restricted Feeding Versus Grazing **Official Title:** Time-Restricted Feeding to Improve Glucose Tolerance and Vascular Condition #### Organization Study ID Info **ID:** PBRC 13017 #### Organization **Class:** OTHER **Full Name:** Pennington Biomedical Research Center ### Status Module #### Completion Date **Date:** 2017-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-03-16 **Type:** ACTUAL **Last Update Submit Date:** 2018-03-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-11 **Type:** ACTUAL #### Start Date **Date:** 2013-07 **Status Verified Date:** 2018-03 #### Study First Post Date **Date:** 2013-07-10 **Type:** ESTIMATED **Study First Submit Date:** 2013-07-03 **Study First Submit QC Date:** 2013-07-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Pennington Biomedical Research Center #### Responsible Party **Investigator Affiliation:** Pennington Biomedical Research Center **Investigator Full Name:** Courtney Peterson **Investigator Title:** Instructor **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** The purpose of this pilot study is to find out what eating meals in a short time period early in the day (time-restricted feeding) versus eating meals spread out during the day (grazing) does to the body's ability to control blood sugar and to the health of its blood vessels. The investigators hypothesize that time-restricted feeding will be more effective at improving glucose tolerance and vascular condition (inflammation and micro- and macro-vascular function) than grazing. **Detailed Description:** Each participant will eat according to one of the two eating schedules (grazing or time-restricted feeding) for 5 weeks, have a 7-week washout period, and then eat according to the other eating schedule for 5 weeks. Measurements of glucose homeostasis and vascular condition will be performed before and after a participant follows each eating schedule. ### Conditions Module **Conditions:** - Prediabetes - Insulin Resistance - Vascular Diseases **Keywords:** - Time-restricted feeding - Intermittent fasting - Prediabetes - Insulin resistance - Glucose tolerance - Insulin sensitivity - Circadian rhythms - Diurnal ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will consume all meals early in the day and within a 6-hour window. **Intervention Names:** - Other: Time-Restricted Feeding **Label:** Time-Restricted Feeding (early in the day eating) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will eat meals spread out over the course of the day. **Intervention Names:** - Other: Grazing **Label:** Grazing **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Time-Restricted Feeding (early in the day eating) **Description:** Time-restricted feeding is a variant of intermittent fasting that involves eating all of one's calories within a few hours each day (typically 4-9 hours), followed by a daily fast of 15-20 hours. **Name:** Time-Restricted Feeding **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Grazing **Description:** Grazing involves eating meals spread out over the course of the day. **Name:** Grazing **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Glucose tolerance and indices of glucose homeostasis will be determined using an Oral Glucose Tolerance Test (OGTT). **Measure:** Change in Glucose Tolerance **Time Frame:** Before and after 5 weeks on each feeding schedule #### Secondary Outcomes **Description:** Macro- and micro-vascular function will be assessed by Radial Artery Applanation Tonometry and by Orthogonal Polarization Spectroscopy. The endpoints measured by these two tests include aortic blood pressure, arterial stiffness, capillary density, and red blood cell velocity. **Measure:** Change in Vascular Function **Time Frame:** Before and after 5 weeks on each feeding schedule **Description:** Serum markers of inflammation, such as C-Reactive Protein (CRP) and inflammatory cytokines, and of metabolic processes will be measured (composite measure). **Measure:** Change in Inflammation and Metabolic Markers **Time Frame:** Before and after 5 weeks on each feeding schedule ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Are male * Overweight: Have a body mass index between 25 and 50 kg/m\^2 inclusive (a number calculated from height and weight) * Are 35-70 years of age * Have a hemoglobin A1C between 5.5 - 6.4% or prior medical indication of prediabetes * Have a blood sugar level between 140 and 199 mg/dL two hours after drinking a sugary solution (OGTT) * Have been eating dinner at least 8.5 hours after eating breakfast at least 90% of the time during the past year * Have not fasted (go for a day without any food) more than 12 days total during the past year * Be willing to eat most meals at Pennington Biomedical and/or under supervision * Not eat any food other than that served by Pennington Biomedical * Not drink any alcohol, juice, or other beverages that have calories other than what is served by Pennington Biomedical * Keep water and no-calorie drinks like tea or diet soda the same during both of the timed eating periods * Be willing to eat your meals according to the fixed schedules Exclusion Criteria: * Have diabetes or are on anti-diabetes medication * Have evidence of cardiovascular disease * Suffer from significant cardiovascular, renal (kidney), cardiac (heart), liver, lung or nervous system disease * Evidence of significant gastrointestinal issues or surgery that impacts nutrient absorption * Regularly use medications such as steroids, beta blockers, and adrenergic-stimulating agents * Are on any regular medicine that has not had the same dose for 1 month or longer * Have a clinically significant abnormality as measured by a blood test * Regularly drink alcohol (more than 2 servings per day) * Have to do any kind of heavy physical activity * Currently perform overnight shift work more than one day a week * Are not able to eat only the food served to you by Pennington Biomedical, while in the study * Are not able to stop drinking alcohol or other drinks with calories (e.g., soda, juice) other than what is served to you by Pennington Biomedical, while in the study **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 35 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Baton Rouge **Country:** United States **Facility:** Pennington Biomedical Research Center **State:** Louisiana **Zip:** 70808 ### References Module #### References **Citation:** Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A. Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2021 Jan 29;1(1):CD013496. doi: 10.1002/14651858.CD013496.pub2. **PMID:** 33512717 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006946 - Term: Hyperinsulinism - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000003920 - Term: Diabetes Mellitus - ID: D000004700 - Term: Endocrine System Diseases - ID: D000006943 - Term: Hyperglycemia ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases ### Condition Browse Module - Browse Leaves - ID: M10370 - Name: Insulin Resistance - Relevance: HIGH - As Found: Insulin Resistance - ID: M17400 - Name: Vascular Diseases - Relevance: HIGH - As Found: Vascular Disease - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14117 - Name: Prediabetic State - Relevance: HIGH - As Found: Prediabetes - ID: M20295 - Name: Glucose Intolerance - Relevance: HIGH - As Found: Prediabetes - ID: M9997 - Name: Hyperinsulinism - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M9994 - Name: Hyperglycemia - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014652 - Term: Vascular Diseases - ID: D000007333 - Term: Insulin Resistance - ID: D000011236 - Term: Prediabetic State - ID: D000018149 - Term: Glucose Intolerance ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03620279 **Brief Title:** Magic Camp for Children With Hemiplegic Cerebral Palsy **Official Title:** Magic Camp for Children With Hemiplegic Cerebral Palsy #### Organization Study ID Info **ID:** IRB-300001044 #### Organization **Class:** OTHER **Full Name:** University of Alabama at Birmingham ### Status Module #### Completion Date **Date:** 2018-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-02-24 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-10-01 **Type:** ACTUAL #### Start Date **Date:** 2018-06-04 **Type:** ACTUAL **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2018-08-08 **Type:** ACTUAL **Study First Submit Date:** 2018-08-02 **Study First Submit QC Date:** 2018-08-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Alabama at Birmingham #### Responsible Party **Investigator Affiliation:** University of Alabama at Birmingham **Investigator Full Name:** Hon K. Yuen, PhD **Investigator Title:** principal investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The proposed study will test the feasibility and effectiveness of a "Magic Camp" in children with spastic hemiplegic cerebral palsy (CP). A single group pretest-posttest design (n=10) will be used to investigate the immediate (2 weeks) and longer-term effect (3 months) of a "Magic Camp" on improving upper limb motor function and health-related quality of life (HRQoL) in children with hemiplegic CP. **Detailed Description:** This project will employ a single group pretest-posttest design to investigate the impact of a "Magic Camp" on the improvement in upper limb motor function, health-related quality of life, and emotional stress among children with spastic hemiplegic CP. After the baseline evaluation, eligible participants will complete one-on-one "magic trick" training 3-hours per day for 2 consecutive weeks. The primary outcome measures will be unimanual function as measured by the Jebsen Taylor Test of Hand Function, bimanual coordination as measured by kinematic parameters using motion analysis, and spontaneous use of the more affected limb in real-life activities that demand the use of both hands as measured by the Children's Hand Experience Questionnaire. Secondary outcome measures will include HRQoL as measured by the Cerebral Palsy Quality of Life Questionnaire, in-depth dyad qualitative interviews of the caregivers and children, and emotional stress as measured by the fingernail cortisol levels. ### Conditions Module **Conditions:** - Cerebral Palsy **Keywords:** - motor training for cerebral palsy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 7 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** These children are diagnosed with cerebral palsy and we will provide motor control training. **Intervention Names:** - Behavioral: Magic camp intervention **Label:** Magic camp intervention **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Magic camp intervention **Description:** Hand-arm bimanual motor skills training **Name:** Magic camp intervention **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Jebsen Taylor Test of Hand Function (JTTHF) is a standardized timed test administered by occupational therapy (OT) students to assess the efficiency of unimanual grasp and release of items with six tasks. Higher scores (i.e., longer duration the participant takes to complete the task) represent poorer unimanual skills **Measure:** Unimanual skill as measured by the Jebsen Taylor Test of Hand Function **Time Frame:** baseline **Description:** Participants will be asked to perform the task with their preferred hand choice at a self-selected pace following by an auditory go-signal. Each trial ends when the button is pressed. Five trials will be collected after 2 practice trials, and outcome measures will be averaged over the 5 trials. Longer time duration it takes for the participant to complete the task represents poorer bimanual coordination. **Measure:** Bimanual coordination as measured by 3-D kinematic motion analysis **Time Frame:** baseline **Description:** CHEQ is a 29-item (parent and child report) questionnaire that evaluates the experience of children in using the more affected hand in activities where usually two hands are required. Percentage use of the more affected hand will be expressed as percentage of independent activities performed bimanually in which the more affected hand is used to stabilize or grip items. Higher percentage (ranging from 0% to 100%) represents higher extent of using the more affected hand. **Measure:** Extent of the more affected hand use in daily bimanual activities as measured by the Children's Hand Experience Questionnaire (CHEQ) **Time Frame:** Baseline **Description:** CPQOL evaluates the well-being of children with CP across several broad domains such as social well-being and acceptance, and emotional well-being. Items are rated on a 9-point scale, and recoded and transformed into scaled scores (transformed to a scale of 1-100) for each domain. An average of the scale scores from all domains (family \& friends, school, communication, health, special equipment, pain and bother, and access to services) is conducted. Higher scores represent better health-related quality of life. **Measure:** Health-related quality of life as measured by the Cerebral Palsy Quality of Life (CPQOL) Questionnaire **Time Frame:** Baseline **Description:** Fingernail samples from every digit will be collected by clipping directly into a Ziploc® bag to avoid losing any parts of the sample. Nail samples will be sent to the Bio-Analytical Redox Biology (BARB) Core Laboratory, University of Alabama at Birmingham (UAB) for analysis. **Measure:** Emotional stress as measured by the amount of cortisol in participants' and their caregivers' fingernails. **Time Frame:** Baseline #### Secondary Outcomes **Description:** Jebsen Taylor Test of Hand Function (JTTHF) is a standardized timed test administered by OT students to assess the efficiency of unimanual grasp and release of items with six tasks. Higher scores (i.e., longer duration the participant takes to complete the task) represent poorer unimanual skills. **Measure:** Unimanual skill as measured by the Jebsen Taylor Test of Hand Function **Time Frame:** from baseline to two weeks **Description:** Participants will be asked to perform the task with their preferred hand choice at a self-selected pace following by an auditory go-signal. Each trial ends when the button is pressed. Five trials will be collected after 2 practice trials, and outcome measures will be averaged over the 5 trials.Longer time duration it takes for the participant to complete the task represents poorer bimanual coordination. **Measure:** Bimanual coordination as measured by 3-D kinematic motion analysis **Time Frame:** from baseline to two weeks **Description:** CHEQ is a 29-item (parent and child report) questionnaire that evaluates the experience of children in using the more affected hand in activities where usually two hands are required. Percentage use of the more affected hand will be expressed as percentage of independent activities performed bimanually in which the more affected hand is used to stabilize or grip items. Higher percentage (ranging from 0% to 100%) represents higher extent of using the more affected hand. **Measure:** Extent of the more affected hand use in daily bimanual activities as measured by the Children's Hand Experience Questionnaire (CHEQ) **Time Frame:** from baseline to two weeks **Description:** CPQOL evaluates the well-being of children with CP across several broad domains such as social well-being and acceptance, and emotional well-being. Items are rated on a 9-point scale, and recoded and transformed into scaled scores for each domain. An average of the scale scores from all domains (family \& friends, school, communication, health, special equipment, pain and bother, and access to services) is conducted. Higher scores represent better health-related quality of life. **Measure:** Health-related quality of life as measured by the Cerebral Palsy Quality of Life (CPQOL) Questionnaire **Time Frame:** from baseline to two weeks **Description:** Jebsen Taylor Test of Hand Function (JTTHF) is a standardized timed test administered by OT students to assess the efficiency of unimanual grasp and release of items with six tasks. Higher scores (i.e., longer duration the participant takes to complete the task) represent poorer unimanual skills. **Measure:** Unimanual skill as measured by the Jebsen Taylor Test of Hand Function **Time Frame:** from two weeks to three months **Description:** Participants will be asked to perform the task with their preferred hand choice at a self-selected pace following by an auditory go-signal. Each trial ends when the button is pressed. Five trials will be collected after 2 practice trials, and outcome measures will be averaged over the 5 trials. Longer time duration it takes for the participant to complete the task represents poorer bimanual coordination. **Measure:** Bimanual coordination as measured by 3-D kinematic motion analysis **Time Frame:** from two weeks to three months **Description:** CHEQ is a 29-item (parent and child report) questionnaire that evaluates the experience of children in using the more affected hand in activities where usually two hands are required. Percentage use of the more affected hand will be expressed as percentage of independent activities performed bimanually in which the more affected hand is used to stabilize or grip items. Higher percentage (ranging from 0% to 100%) represents higher extent of using the more affected hand. **Measure:** Extent of the more affected hand use in daily bimanual activities as measured by the Children's Hand Experience Questionnaire (CHEQ) **Time Frame:** from two weeks to three months **Description:** CPQOL evaluates the well-being of children with CP across several broad domains such as social well-being and acceptance, and emotional well-being. Items are rated on a 9-point scale, and recoded and transformed into scaled scores for each domain. An average of the scale scores from all domains (family \& friends, school, communication, health, special equipment, pain and bother, and access to services) is conducted. Higher scores represent better health-related quality of life. **Measure:** Health-related quality of life as measured by the Cerebral Palsy Quality of Life (CPQOL) Questionnaire **Time Frame:** from two weeks to three months **Description:** Fingernail samples from every digit will be collected by clipping directly into a Ziploc® bag to avoid losing any parts of the sample. Nail samples will be sent to the BARB Core Laboratory, UAB for analysis. **Measure:** Emotional stress as measured by the amount of cortisol in participants' and their caregivers' fingernails. **Time Frame:** from baseline to three months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * spasticity with Modified Ashworth Scale grades between 1 and 3; * ability to lift the more affected arm 15 cm above a table surface; * impairment of hand function at levels I to III of the Manual Activity Classification System * ability to grasp and release light objects with the more affected hand * largely nonuse of the more affected hand in daily activities as determined by the Pediatric Motor Activity Log * are interested in learning magic tricks * have the cognitive and social ability to participate in a camp setting; * ability to follow directions in English; and * ability to remember simple sequences of actions to perform magic tricks. Exclusion Criteria: * severe muscle spasticity or fixed contracture in the more affected limb that limits functional arm and hand use * dystonia * severe visual or auditory disorders that prevent learning and carrying out the magic tricks * serious or recurring medical complications * participation in intensive upper limb intervention and/or musculoskeletal and tone management treatments, dorsal rhizotomy, or surgery on the upper limb in the previous 6 months or anticipated within subsequent 6 months * start muscle relaxant within the last 3 months; or * plan to move to another state within the next 6 months. **Maximum Age:** 18 Years **Minimum Age:** 9 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham **State:** Alabama **Zip:** 35294 #### Overall Officials **Official 1:** **Affiliation:** University of Alabama at Birmingham **Name:** Hon K Yuen, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000001925 - Term: Brain Damage, Chronic - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5796 - Name: Cerebral Palsy - Relevance: HIGH - As Found: Cerebral Palsy - ID: M13157 - Name: Paralysis - Relevance: HIGH - As Found: Palsy - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M5207 - Name: Brain Injuries - Relevance: LOW - As Found: Unknown - ID: M5202 - Name: Brain Damage, Chronic - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010243 - Term: Paralysis - ID: D000002547 - Term: Cerebral Palsy ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04011579 **Acronym:** MS-FIT **Brief Title:** Pilates Training in Multiple Sclerosis **Official Title:** Multiple Sclerosis Fitness Intervention Training With Pilates Exercises #### Organization Study ID Info **ID:** FISM 2019MSFIT #### Organization **Class:** OTHER **Full Name:** Fondazione Italiana Sclerosi Multipla ### Status Module #### Completion Date **Date:** 2023-10-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-22 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-10-20 **Type:** ACTUAL #### Start Date **Date:** 2022-03-15 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2019-07-08 **Type:** ACTUAL **Study First Submit Date:** 2019-06-11 **Study First Submit QC Date:** 2019-07-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fondazione Italiana Sclerosi Multipla #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** To date, despite recent advances in MS care including rehabilitation interventions, many PwMS are unable to access these developments due to limited mobility, fatigue and related issues, and costs associated with travel. Thus, physical activity at home could be a new way to deliver exercises to the patients. Although Pilates did not show any significant advantage over standardized physical therapy in the current literature, it is a good method to promote physical activity, sensorimotor integration and cognitive stimulation. Thus, it could be a treatment option to improve fatigue, balance and walking abilities in PwMS; consequently, Pilates could be suggested by the clinician as a physical activity to be integrated in the daily life. This possibility could be made more feasible using new tools such as those offered by low cost devices. The main MS-FIT project purposes are to provide and to test a tool based on serious game concept of Pilates-inspired exercises for daily use at home, by mixing the entertainment aspects typical of the videogames and the possibility to perform physical activity. The MS-FIT tool does not pursue therapeutic aims as rehabilitation does, but it could have a positive impact on prevention and health in MS. MS-FIT, by using the Microsoft Kinect Motion Controller Xbox or similar to deliver adapted physical activity, offers the possibility to transform the Pilates exercises into a virtual reality game. MS-FIT, through a multicentre approach, would provide: * a feasibility study in order to: * refine the tool for the final customized version to be used in a RCT MS study * assess the tool for PwMS in terms of technology acceptability and satisfaction-to-use * assess the process of recruitment, the adherence to the intervention, the dropout rate and identify potential issues * assess human resources necessary for the RCT * estimate the effect of the intervention and its variance necessary to calculate the appropriate sample size for the RCT * a RCT study in order to evaluate the effect of a physical activity intervention of exercises inspired to Pilates self-managed at home in terms on PwMS **Detailed Description:** Devices and technologies for at-home interventions could provide to PwMS with mild disability useful tools to successfully maintain own physical, cognitive and emotional status by performing at-home physical activity/exercises and avoiding outpatient interventions. Together, new devices and technologies could help in overcoming all barriers (i.e. transportations, working time, etc.) hindering the adherence to and, consequently, efficacy of the outpatient treatments. Although Pilates did not show any significant advantage over standardized physical therapy in the current literature, it is a good method to promote physical activity, sensorimotor integration and cognitive stimulation. Thus, it could be a treatment option to improve fatigue, balance and walking abilities in PwMS; consequently, Pilates could be suggested by the clinician as a physical activity to be integrated in the daily life. This possibility could be made more feasible using new tools such as those offered by low cost devices. The main MS-FIT project purposes are to provide and to test a tool based on serious game concept of Pilates-inspired exercises for daily use at home, by mixing the entertainment aspects typical of the videogames and the possibility to perform physical activity. The MS-FIT tool does not pursue therapeutic aims as rehabilitation does, but it could have a positive impact on prevention and health in MS. MS-FIT, by using the Microsoft Kinect Motion Controller Xbox or similar to deliver adapted physical activity, offers the possibility to transform the Pilates exercises into a virtual reality game. MS-FIT, through a multicentre approach, would provide: * Feasibility study * RCT study All the 14 participating centres will select a dedicated therapist who will be responsible for patient training in using the MS-FIT tool. All the subjects recruited following the inclusion/exclusion criteria will sign an informed consent and all the procedures (feasibility and RCT) will be in agreement with the Declaration of Helsinki (1964) and approved by Local Ethical Committee. No trial-specific procedures will be conducted before informed consent has been obtained, and participants will be reminded that they may withdraw from the trial at any time without it affecting the quality of their care in the future. Participants with relapses during the period of their involvement in the project will be considered as drop out and will be considered in the analysis for the entire period of study participation. Feasibility study Primary objective: • the refinement of the tool for the final customized version to be used in a RCT MS study. The primary objective will be reached by fixing eventual bugs relieved during the feasibility study and taking into account results from the assessment in terms of technology acceptability and satisfaction-to-use, adherence to the intervention, intervention safety and the physical effects of the intervention. Secondary Objectives: * the estimation of human resources necessary for the RCT. * the estimation of the effect of the intervention and its variance necessary to calculate the appropriate sample size for the RCT. Due to the nature of the feasibility study and based on previous literature showing that a sample size of 25-40 subjects per arm is adequate for a feasibility trial, the investigators will recruit 28 PwMS per arm. All the 14 participating centres will recruit a total of 56 recruited patients following the inclusion and exclusion criteria. In the range of EDSS inclusion criteria 28 subjects will be recruited with lower disability (EDSS 2-3) and 28 with higher disability (EDSS of 3.5 or 4). For both levels the subjects will be randomized into two groups: MSFITFeas (MS-FIT at-home + "unspecific physical activities") and CTRLFeas ("unspecific physical activities"). Randomization will be provided by an independent randomization service at FISM accessed via a web-based system, using computer-based block randomization (1 factor: EDSS score 2-3 and 3.5-4). Patient will be allocated to MSFITFeas and CTRLFeas in a 1:1 ratio. Confirmation emails will be sent to Centres PI. The MSFITFeas group will self-manage MS-FIT at-home for 6 weeks, performing at least 3 sessions/week for a total of 30 minutes of exercises (also distributed during the day with a minimum slot of 10 minutes) for each session. During this period Xbox One and Microsoft Kinect 2.0 will be delivered to the participants for the aims of the study. Before starting the at-home intervention each subject will be trained to the use of the platform by a therapist. No rehabilitative interventions except sphincter and speech rehabilitation and psychological support, are admitted for the 6 weeks of participation to the project. The execution of unspecific physical activities, if not already practiced, will be suggested to the participants. For the 6 weeks of participation to the project CTRLFeas will be similar to MSFITFeas group except for the execution of MS-FIT at-home. The protocol for the Feasibility study will consist on (Figure 2): * T0 evaluation (PRE) * 6 weeks of intervention * MSFITFeas: unspecific physical activities + MS-FIT at-home * CTRLFeas: unspecific physical activities * T1 evaluation (POST) The evaluation for the Feasibility study are described in the section Outcome Measures. Deliverables Deliverables of the Feasibility study will be the final customized tool, a set of indications for the management of the RCT, the sample size estimation for the RCT. Focus group A nested qualitative study on 14 participants will explore patients' experiences of MS-FIT via Focus Group Meeting (FGM). The objectives are to provide insight into the quantitative results, explore strengths and limitations of the intervention with MS-FIT, so as to guide the RCT. The report of each FGM analysis will be submitted to FGM participants for review (respondent validation). Deliverables Deliverables of the nested qualitative study will be the delivery of the report of the FGM analysis. RCT study Primary Objective: • evaluation of the change in TUG. Secondary Objectives: * evaluation of the physical effects also in terms of self-reported outcome, upper limb performances, resistance in walking and physical activity, cognitive and psychosocial effects, quality of life and wellbeing. Differences in physical and cognitive performances due to the genetic features will be evaluated also considering subgroups identified through the polymorphism analysis. * evaluation of the acceptability and satisfaction-to-use, adherence to the intervention, intervention safety through the measurements of endpoint already listed for the Feasibility study. The RCT sample size will be definitively calculated based on the results from the feasibility study. However, by considering the literature about Pilates in MS, the investigators can preliminary estimate the needed sample size. In particular, the investigators refer to the TUG post-intervention improvement found by Karlon et al. in a group of PwMS performing Pilates. For our aim, the investigators can consider this result even if no differences between Pilates group and control group (Physiotherapy) were found. Pilates group improved the performance in TUG of about 1.8s, that could be considered as clinically relevant for PwMS. By considering a variability of about 3.4s, a power of 80%, a level of significance (two sided) of 5% and a potential loss of 15% of patients at follow-up, the estimation of the necessary sample size consists of approximately 63 subjects for the experimental group (a total of 126). All the 14 participating centres will be involved in the patients' enrolment. The subjects will be randomized into two groups: MSFITRCT (MS-FIT at-home + "unspecific physical activities") and CTRLRCT ("unspecific physical activities"). The randomization will be carried out using a web based procedure and will be centrally managed. A stratified minimization/adaptive algorithm will be used in order to balance the baseline EDSS (2-3 vs 3.5-4) factors across the two groups. The MSFITRCT group will self-manage MS-FIT at-home for 12 weeks, performing at least 3 sessions/week for a total of 30 minutes of exercises (also distributed during the day with a minimum slot of 10 minutes) for each session. During this period Xbox One and Microsoft Kinect 2.0 will be delivered to the participants for the aims of the study. Before starting the at-home intervention each subject will be trained to the use of the platform by a therapist. The follow-up (FU) evaluation will be after 6 weeks since the end of the intervention. No rehabilitative interventions except sphincter and speech rehabilitation and psychological support, are admitted for the 18 (12 + 6) weeks of participation to the project. The execution of unspecific physical activities, if not already practiced, will be suggested to the participants. For the 18 (12 + 6) weeks of participation to the project CTRLFeas will be similar to MSFITFeas group except for the execution of MS-FIT at-home. At the end of the 18 weeks, the participants of the CTRLRCT group will be offered the MS-FIT intervention. The requirement that the enrolled patients will have not to perform any supervised physical activity or rehabilitative intervention is in line with recent studies showing that most of PwMS with mild disability (78.34% EDSS \<4) were not treated with rehabilitation. The subjects involved in the feasibility study will be excluded from the RCT study in order to avoid bias effects. The protocol design for the RCT study will consist on (Figure 3): * T0 evaluation (PRE) * 12 weeks of intervention * MSFITRCT: unspecific physical activities + MS-FIT at-home * CTRLRCT: unspecific physical activities * T1 evaluation (POST) * T2 evaluation (FU) - after 6 weeks from T1 The evaluation for the RCT study are described in the section Outcome Measures. Moreover, blood samples will be collected at T0 to investigate if genetic polymorphisms of candidate regulators of neuronal plasticity could be correlated to the response to the proposed protocol. According to previous report MS subjects of the two RCT groups could be subdivided in subgroups with respect to the polymorphism features. For example, for the CNR1 gene the subdivision could be based on the number of AAT repetitions (short AAT: homozygous or heterozygous for allele with ≤11 repeats of AAT triplets; long AAT: homozygous for allele with ≥12 repeats of AAT triplets). Differences among subgroups in terms of physical and cognitive performances will be evaluated. In particular, all patients will be genotyped for a total of 55 genetic polymorphisms of 23 potential regulators, like: Homer1; AKT1; RAPTOR; D2R; GAPD; CHAT; p53; BRCA2; LIG4; XRCC5; CYP3A4; NBS1; MDM2; CNR1, ATTn; CNR2; GRIN1; GRIN2B; TRPV1; FAAH, COMPT; (Brain-derived neurotrophic factor) BDNF. Blood sample will be assessed from participants early in the morning after awakening (8h). To synchronize the sample for lifestyle variables, subjects were requested to avoid excessive physical activity the last three days before the blood sampling, sleep for 7-8h the night before study, avoid starving, and eat a usual breakfast in the morning (approximately 1h before the time of the breakfast). The samples will be collected by each participant centre and shipped to the IRCCS Neuromed, Pozzilli, Isernia (Prof. Diego Centonze) for the analyses. Deliverables Deliverables will be the report of the results of the trial and the final guidelines to make available and easy-to-use the MS-FIT tool Criteria for Premature Withdrawal Criteria for the premature withdrawal are: 1. Patients withdrawal of the consent anytime; 2. Any medical conditions that the investigator determines jeopardize the patient's safety if she/he continues the study and/or study results; 3. Patient's no-compliance to complete the study procedures 4. MS Treatment changes during the study ### Conditions Module **Conditions:** - Multiple Sclerosis - Physical Activity **Keywords:** - Physical activity - Pilates - Fitness ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 126 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The MSFIT group will self-manage Pilates exercises at-home through a tool based on XBox Kinect for 12 weeks, performing at least 3 sessions/week for a total of 30 minutes of exercises for each session(also distributed during the day with a minimum slot of 10 minutes). No rehabilitative interventions except sphincter and speech rehabilitation and psychological support, are admitted for the 12 weeks of participation to the project and the following 6 weeks before Follow-up evaluations (a total of 18 weeks). The execution of unspecific physical activities, if not already practiced, will be suggested to the participants. **Intervention Names:** - Other: MSFIT **Label:** MSFIT **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No rehabilitative interventions except sphincter and speech rehabilitation and psychological support, are admitted for the 12 weeks of participation to the project and the following 6 weeks before Follow-up evaluations (a total of 18 weeks). The execution of unspecific physical activities, if not already practiced, will be suggested to the participants. **Label:** CTRL **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - MSFIT **Description:** MSFIT, by using the Microsoft Kinect Motion Controller Xbox to deliver adapted physical activity, offers the possibility to transform the Pilates exercises into a virtual reality game. Each exercise is implemented with different levels of difficulty in order to allow the adaptation to the capacities of the user. **Name:** MSFIT **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The Timed "Up and Go" Test measures, in seconds, the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm, arm height 65 cm), walk a distance of 3 meters (approximately 10 feet), turn, walk back to the chair, and sit down. **Measure:** Change in Timed Up & Go (TUG) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 #### Secondary Outcomes **Description:** The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk.The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. **Measure:** Change in Timed 25-Foot Walk (T25FW) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The AI is a rating scale developed by Hauser et al (1983) to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. Scores range from 0 (asymptomatic and fully active) to 10 (bedridden). The patient is asked to walk a marked 25-foot course as quickly and safely as possible. The examiner records the time and type of assistance (e.g., cane, walker, crutches) needed. **Measure:** Change in Ambulation Index (AI) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The 2-minute walk test (2WT) is an easy to perform and practical test that has been used in the assessment of patients with a variety of diseases. It simply measures the distance that a patient can walk on a flat, hard surface in a period of 2 minutes. **Measure:** Change in 2-Minutes Walking Test (2WT) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The technology acceptance model (TAM) is an information systems theory that models how users come to accept and use a technology. The model suggests that when users are presented with a new technology, a number of factors influence their decision about how and when they will use it, notably: the Perceived usefulness and the Perceived ease-of-use. **Measure:** Change in Technology Acceptance Model (TAM) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The CSQ-8 is the most used self-report questionnaires constructed to measure satisfaction with services received by individuals and families. The item score ranges from 1 to 4 and the maximum total score is 32. Higher values mean met needs. **Measure:** Change in Client Satisfaction Questionnaire-8 (CSQ-8) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** Evaluation of the level of satisfaction with telehealth from the perspective of clinic patients.The item score ranges from 1 to 4 and the maximum total score is 40. Higher values mean excellent satisfaction. **Measure:** Change in Telehealth Satisfaction Scale (TeSS) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** Number of sessions actually performed **Measure:** Adherence to the intervention based on sessions **Time Frame:** T1: after 12 weeks of intervention **Description:** Number of dropout **Measure:** Adherence to the intervention based on drop-out **Time Frame:** T1: after 12 weeks of intervention **Description:** The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a self-report measure of the impact of MS on the individual's walking ability. The item score ranges from 1 to 5 and the maximum total score is 60. Lower values mean lower disease impact on walking. **Measure:** Change in Twelve Item MS Walking Scale (MSWS-12) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** Balance performance subjective evaluation on a scale of 10 points. Subjects have to indicate the self-perceived balance performance in a line ranging from 0 to 10. **Measure:** Change in Visual Analogue Scale (VAS) (0-10) for balance performance **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The Nine-Hole Peg Test (9HPT) is a test used to measure finger dexterity in patients with various neurological diagnoses. **Measure:** Change in Nine-Hole Peg Test (9HPT) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** MFIS is a 21-items questionnaire and provides a subjective assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. The item score ranges from 0 to 4 and the maximum total score is 84. Lower values mean lower self-perceived effect of fatigue. Physical subtest range from 0 to 36. Cognitive subtest ranges from 0 to 40. Psychosocial subtest ranges from 0 to 8. **Measure:** Change in Modified Fatigue Impact Scale (MFIS) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The Brief International Cognitive Assessment for MS (BICAMS) battery includes Symbol Digit Modality Test (SDMT) for information processing, Californian Verbal Learning Test (CVLT) for verbal memory, Visuospatial Memory Test (BVMT) for spatial memory. In SDMT subjects have to assign as fast and as accurate as possible the numbers 1-9 to predefined symbols in 90s. In VLMT the examiner reads aloud and consecutively the 15 words to the participant who in return has to recall as many words as possible. This procedure is repeated 5 times. The sum score is the number of correctly recalled words. In BVMT subjects have to encode 6 geometrical figures and memorize their precise location during presentation of 10s. Immediately afterwards, subjects have to draw the memorized figures in the right location. The procedure is repeated 3 times. Depending on figure and exact location accuracy, a scoring from 0 to 2 points for each figure is given. The total recall score is the sum of the three trials. **Measure:** Change in Brief International Cognitive Assessment for MS (BICAMS) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment. PGIC is a 7 point scale depicting a patient's rating of overall improvement. It has the options "very much improved", "much improved", "minimally improved", "no change", "minimally worsened", "much worsened", and "very much worsened". **Measure:** Change in Patient Global Impression of Change (PGIC) with a 7-points scale **Time Frame:** T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument. There is no single overall score for the MSQOL-54. Two summary scores - physical health and mental health - can be derived from a weighted combination of scale scores. In addition, there are 12 subscales: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. There are also two single-item measures: satisfaction with sexual function and change in health. See the original article describing the development and testing of the MSQOL-54 (Vickrey et al, 1995) for details. Administration forms and scoring instructions can be downloaded. **Measure:** Change in Multiple Sclerosis Quality of Life-54 (MSQoL54) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** PWB measures 6 aspects of wellbeing/happiness that respondents rate statements on a scale of 1 to 6, with 1 indicating strong disagreement and 6 indicating strong agreement. Self-acceptance: High scorer: Possesses a positive attitude toward the self; Low scorer: Feels dissatisfied with self. Positive relations with others: Higher score: Has warm, satisfying, trusting relationships with others; Lower score: Has few close, trusting relationships with others. Autonomy: High scorer: Is self-determining and independent; Low scorer: Is concerned about the expectations and evaluations of others. Environmental mastery: High scorer: Has a sense of mastery and competence in managing the environment; Low scorer: Has difficulty managing everyday affairs; Purpose in life: High scorer: Has goals in life and a sense of directedness; Low scorer: Lacks a sense of meaning in life. Personal growth: High scorer: Has a continued development feeling; Low scorer: Has a personal stagnation sense. **Measure:** Change in Psychological Well-Being Scales (PWB) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** IPAQ is a method for physical activity assessment of time spent in several domains. In particular 5 domains are considered: JOB-RELATED; TRANSPORTATION; HOUSEWORK, HOUSE MAINTENANCE, AND CARING FOR FAMILY; RECREATION, SPORT, AND LEISURE-TIME; TIME SPENT SITTING. Three levels of physical activity are proposed: Low: Those individuals who not meet criteria for categories 2 or 3. Moderate: * 3 or more days of vigorous activity of at least 20 minutes per day * 5 or more days of moderate-intensity activity or walking of at least 30 minutes per day * 5 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 600 (metabolic equivalent)MET-min/week. High: * Vigorous-intensity activity on at least 3 days and accumulating at least 1500 MET-minutes/ week OR * 7 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 3000 MET-minutes/week. **Measure:** Change in International Physical Activity Questionnaire (IPAQ) **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** Assessment of physical activity in terms of total energy expenditure. The results were expressed in a weekly value \[kcal/week\] after dividing the calcu- lated 6-month energy expenditure by 26 weeks. The following ranges of activity intensity were used: low \[\< 4 MET\], medium \[4 - \< 6 MET\] and high \[≥ 6 MET\], where 1 MET equals the resting metabolic rate, which is approximately 3.5 ml oxygen kg-1 body weight per min-1. **Measure:** Change in Minnesota Leisure-Time Physical Activity Questionnaire **Time Frame:** T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1 **Description:** Blood samples at baseline to genotype the subjects. **Measure:** Correlation between genetic polymorphisms and response to protocol **Time Frame:** T0: before intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All disease courses of MS * Expanded Disability Status Scale (EDSS) 2-4 * Hospital Anxiety and Depression Scale (HADS) \< 10 in the two subset of anxiety and depression * Berg Balance Scale (BBS) \> 46 * Mini-Mental State Examination (MMSE) \> 24 * At least 1 month without having been treated with rehabilitation * Willingness to sign informed consent Exclusion Criteria: * Visual deficits that could compromise the use of MS-FIT * Relapses in the last 3 months **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Genoa **Country:** Italy **Facility:** Italian Multiple Sclerosis Foundation **Zip:** 16149 #### Overall Officials **Official 1:** **Affiliation:** Italian Multiple Sclerosis Foundation **Name:** Giampaolo Brichetto **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01783379 **Acronym:** MIMIC **Brief Title:** Pharmacokinetics of Micafungin in Patients Intensive Care Unit **Official Title:** Pharmacokinetics of Micafungin (Mycamine ®) Given Intravenously as Therapy to Patients With an Invasive Fungal Infection in the Intensive Care Unit - a Search for Co-variates #### Organization Study ID Info **ID:** UMCN AKF 12.05 #### Organization **Class:** OTHER **Full Name:** Radboud University Medical Center ### Status Module #### Completion Date **Date:** 2014-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-11-30 **Type:** ACTUAL **Last Update Submit Date:** 2020-11-26 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-03 **Type:** ACTUAL #### Start Date **Date:** 2013-01 **Status Verified Date:** 2020-11 #### Study First Post Date **Date:** 2013-02-04 **Type:** ESTIMATED **Study First Submit Date:** 2013-01-09 **Study First Submit QC Date:** 2013-01-31 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Radboud University Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In this trial, our goal is to determine the pharmacokinetics of micafungin in a non-selected cohort of patients with suspected or proven invasive fungal infections. Patients will receive micafungin for the period necessary to achieve clinical and / or mycological cure. An attempt will be made to have 2 PK curves, one full and one limited sampling on days 3 (n=9) and 7 (n=5). Furthermore, we will be able to determine intra-individual variability. On non-PK days, trough samples will be taken to determine the time to steady state. All samples will be taken just prior to the morning dose of micafungin. All infusion rates will be according to the SPC label information. Patients are considered to be evaluable if at least the first PK curve has been completed. Two moments of PK analysis will enable us to determine whether there is an increase over time in exposure if steady state has not been reached. **Detailed Description:** Whilst micafungin (Mycamine®) has much to offer, little is known about its pharmacokinetic profile in ICU patients with specific co-morbidities such as obesity, hypoalbumenia, and severe liverfunction disturbances. Also, ICU patients are known to experience changes in pharmacokinetics (PK) due to changes in hemodynamics, extracorporeal elimination techniques, interacting comedication, etc. Based on criteria outlined below, micafungin may prove to be the drug of choice in this cohort of patients. Therefore it seems prudent to conduct a trial in a cohort of patients who receive micafungin but with co-variates that may be of influence to the pharmacokinetic profile. To build a valid pharmacokinetic model, all patients on micafungin will be included in the analysis and used for model building. Co-variates that will be explored are at least: obesitas, liverfunction, albumin, creatinin-clearance. Simulations will be performed to determine if adequate exposure is reached under different patho-physiological conditions. In conclusion: this trial is on determining the PK of micafungin in a non-selected cohort of patients with suspected or proven invasive fungal infections. Most important covariates will be modelled using advanced mathematical techniques. Micafungin may prove to be beneficial over the other two echinocandins in terms of limited factors that impact PK. This has to be proven in a prospective trial. ### Conditions Module **Conditions:** - Invasive Fungal Infection **Keywords:** - invasive fungal infection - micafungin - intensive care - pharmacokinetics ### Design Module #### Bio Spec **Description:** blood samples for pharmacokinietic analysis will be collected **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** ICU patients with an invasive fungal infection on micafungin treatment **Intervention Names:** - Drug: micafungin **Label:** ICU patient on micafungin ### Interventions #### Intervention 1 **Arm Group Labels:** - ICU patient on micafungin **Description:** 100mg/day infusion in 1 hour **Name:** micafungin **Other Names:** - Mycamine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** AUC0-tau \[mg\*g/L\] of micafungin given to ICU patients. Other pharmacokinetic parameters will be assessed as well. **Measure:** micafunigin AUC **Time Frame:** Day 3 and Day 7 #### Secondary Outcomes **Description:** co-variates of influence on the pharmacokinetics of micafungin. Specific co-variates are of high interest to the researchers: high body weight (including obese patients, defined as BMI\> 30 kg/m2), hypo-albuminaemia, clearance pathways, impact of extracorporeal clearance system (ECMO, CVVH). **Measure:** covariates **Time Frame:** 17 days **Description:** To determine whether adequate exposure is attained in ICU patients **Measure:** exposure **Time Frame:** 17 days **Description:** To determine the safety of micafungin in this patient population **Measure:** number of adverse events **Time Frame:** 17 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patient is admitted to an ICU 2. Subject is at least 18 years of age on the day of the first dosing 3. If subject is female: neither pregnant nor able to become pregnant and is not nursing an infant 4. Subject has been treated with micafungin for a maximum of two days before enrolment in this trial 5. Is managed with a central venous catheter or an arterial catheter Exclusion Criteria: 1. Is known to be hypersensitive to echinocandin antifungal agents 2. Documented history of sensitivity to excipients similar to those found in the micafungin preparation 3. Known of positive HIV test or positive hepatitis B or C test in history 4. History of or current abuse of drugs, alcohol or solvents 5. Has previously participated in this trial **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** All patients receiving micafungin for the treatment or suspicion of an invasive fungal infection will be included. At least 20 patients will be included to obtain 16 evaluable patients. If recruitment of 20 patients is achieved within one year, more patients can be included. A formal sample size cannot be performed for several reasons but the sample size is rather based on the general assumption that 16 patients are sufficient to have a descriptive PK approach. ### Contacts Locations Module #### Locations **Location 1:** **City:** Arnhem **Country:** Netherlands **Facility:** Rijstate Hospital **Location 2:** **City:** Ede **Country:** Netherlands **Facility:** Gelderse Vallei Hospital **Location 3:** **City:** Nijmegen **Country:** Netherlands **Facility:** Canisius Wilhelmina Ziekenhuis **Location 4:** **City:** Nijmegen **Country:** Netherlands **Facility:** Radboud University Nijmegen Medical Centre #### Overall Officials **Official 1:** **Affiliation:** Radboud University Medical Center **Name:** R Bruggemann **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Lempers VJ, Schouten JA, Hunfeld NG, Colbers A, van Leeuwen HJ, Burger DM, Verweij PE, Pickkers P, Bruggemann RJ. Altered Micafungin Pharmacokinetics in Intensive Care Unit Patients. Antimicrob Agents Chemother. 2015 Aug;59(8):4403-9. doi: 10.1128/AAC.00623-15. Epub 2015 May 11. **PMID:** 25963988 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001423 - Term: Bacterial Infections and Mycoses ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: HIGH - As Found: Fungal Infections - ID: M1099 - Name: Invasive Fungal Infections - Relevance: HIGH - As Found: Invasive Fungal Infections - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000009181 - Term: Mycoses - ID: D000072742 - Term: Invasive Fungal Infections ### Intervention Browse Module - Ancestors - ID: D000000935 - Term: Antifungal Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1829 - Name: Micafungin - Relevance: HIGH - As Found: AMP - ID: M6252 - Name: Clotrimazole - Relevance: LOW - As Found: Unknown - ID: M11796 - Name: Miconazole - Relevance: LOW - As Found: Unknown - ID: M4254 - Name: Antifungal Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077551 - Term: Micafungin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03845179 **Brief Title:** GA 6: The Blood Glucose-lowering Effect of Glucose-dependent Insulinotropic Polypeptide **Official Title:** The Blood Glucose-lowering Effect of Glucose-dependent Insulinotropic Polypeptide #### Organization Study ID Info **ID:** H-18040916 #### Organization **Class:** OTHER **Full Name:** University Hospital, Gentofte, Copenhagen ### Status Module #### Completion Date **Date:** 2020-02-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-03-16 **Type:** ACTUAL **Last Update Submit Date:** 2021-03-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-02-28 **Type:** ACTUAL #### Start Date **Date:** 2019-05-29 **Type:** ACTUAL **Status Verified Date:** 2021-03 #### Study First Post Date **Date:** 2019-02-19 **Type:** ACTUAL **Study First Submit Date:** 2019-02-11 **Study First Submit QC Date:** 2019-02-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Gentofte, Copenhagen #### Responsible Party **Investigator Affiliation:** University Hospital, Gentofte, Copenhagen **Investigator Full Name:** Signe Stensen **Investigator Title:** MD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study will investigate if the effect of DPP-4 inhibitors is mediated in part by Glucose-dependent insulinotropic polypeptide. **Detailed Description:** A randomized, placebo controlled study. Using a GIP receptor antagonist, we will investigate the glucose lowering effect of GIP during treatment with DPP-4 inhibitors. ### Conditions Module **Conditions:** - Type2 Diabetes ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Randomized, placebo-controlled, cross-over. ##### Masking Info **Masking:** DOUBLE **Masking Description:** Double blinded study. Both participants and investigators are blinded to interventions. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Placebo tablet for placebo treatment period. Following treatment: 2 separate interventions/study days (placebo infusion and GIP receptor antagonist) **Intervention Names:** - Other: Placebo - Other: GIP receptor antagonist - Other: Placebo tablet **Label:** Placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** DPP-4 inhibitor treatment for active treatment period. Following treatment: 2 separate interventions/study days (placebo infusion and GIP receptor antagonist) **Intervention Names:** - Other: Placebo - Other: GIP receptor antagonist - Drug: DPP-4 inhibitor **Label:** DPP-4 inhibitor **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - DPP-4 inhibitor - Placebo **Description:** Saline infusion **Name:** Placebo **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - DPP-4 inhibitor - Placebo **Description:** Used for infusion on study days **Name:** GIP receptor antagonist **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - DPP-4 inhibitor **Description:** Oral administration of DPP-4 inhibitor in active treatment period **Name:** DPP-4 inhibitor **Other Names:** - Sitagliptin **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Placebo **Description:** Oral administration of placebo tablet in placebo treatment period **Name:** Placebo tablet **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Measures from ultrasound sonography **Measure:** Gallbladder volume **Time Frame:** 5 hours **Description:** Repeated measures **Measure:** Systolic and diastolic blood pressure **Time Frame:** 5 hours **Description:** Repeated measures **Measure:** heart rate **Time Frame:** 5 hours #### Primary Outcomes **Description:** Concentrations of C-peptide during GIP receptor antagonism compared to placebo **Measure:** C-peptide **Time Frame:** 5 hours #### Secondary Outcomes **Description:** Concentrations of plasma glucose during GIP receptor antagonism compared to placebo **Measure:** Plasma glucose **Time Frame:** 5 hours **Description:** Concentrations of insulin during GIP receptor antagonism compared to placebo **Measure:** Insulin **Time Frame:** 5 hours **Description:** Concentrations of total and intact GIP during GIP receptor antagonism compared to placebo **Measure:** Total and intact GIP **Time Frame:** 5 hours **Description:** Concentrations of total and intact GLP-1 during GIP receptor antagonism compared to placebo **Measure:** Total and intact GLP-1 **Time Frame:** 5 hours **Description:** Concentrations of glucagon during GIP receptor antagonism compared to placebo **Measure:** Glucagon **Time Frame:** 5 hours **Description:** Concentrations of CTX during GIP receptor antagonism compared to placebo **Measure:** CTX **Time Frame:** 5 hours **Description:** Concentrations of lipids during GIP receptor antagonism compared to placebo **Measure:** Lipids **Time Frame:** 5 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * type 2 diabetes, treatment: lifestyle changes or metformin * HbA1c \< 75 mmol/mol Exclusion Criteria: * diagnosed liver disease * eGFR \< 60 ml/min/1,73m2 * NYHA III or IV * anemia. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Copenhagen **Country:** Denmark **Facility:** Center for Clinical Metabolic Research **State:** Hellerup **Zip:** 2900 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Stensen S, Gasbjerg LS, Rosenkilde MM, Vilsboll T, Holst JJ, Hartmann B, Christensen MB, Knop FK. Endogenous Glucose-Dependent Insulinotropic Polypeptide Contributes to Sitagliptin-Mediated Improvement in beta-Cell Function in Patients With Type 2 Diabetes. Diabetes. 2022 Oct 1;71(10):2209-2221. doi: 10.2337/db22-0059. **PMID:** 35796651 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000054795 - Term: Incretins - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000011480 - Term: Protease Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M27957 - Name: Dipeptidyl-Peptidase IV Inhibitors - Relevance: HIGH - As Found: Artery Bypass Graft - ID: M335 - Name: Sitagliptin Phosphate - Relevance: HIGH - As Found: Anesthetic - ID: M8866 - Name: Gastric Inhibitory Polypeptide - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M27905 - Name: Incretins - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M19609 - Name: HIV Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M14343 - Name: Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068900 - Term: Sitagliptin Phosphate - ID: D000054873 - Term: Dipeptidyl-Peptidase IV Inhibitors ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05708079 **Brief Title:** Multidimensional Evaluation of Patients With Acute Ischemic Stroke Undergoing Pharmacological and Endovascular Revascularization Procedures for the Identification of Positive Prognostic Factors **Official Title:** Multidimensional Evaluation of Patients With Acute Ischemic Stroke Undergoing Pharmacological and Endovascular Revascularization Procedures for the Identification of Positive Prognostic Factors #### Organization Study ID Info **ID:** 3004 #### Organization **Class:** OTHER **Full Name:** Fondazione Policlinico Universitario Agostino Gemelli IRCCS ### Status Module #### Completion Date **Date:** 2023-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-02-08 **Type:** ACTUAL **Last Update Submit Date:** 2023-02-06 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2020-06-01 **Type:** ACTUAL **Status Verified Date:** 2023-02 #### Study First Post Date **Date:** 2023-02-01 **Type:** ACTUAL **Study First Submit Date:** 2023-01-23 **Study First Submit QC Date:** 2023-01-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fondazione Policlinico Universitario Agostino Gemelli IRCCS #### Responsible Party **Investigator Affiliation:** Fondazione Policlinico Universitario Agostino Gemelli IRCCS **Investigator Full Name:** Alexandre Andrea, MD MSc **Investigator Title:** MD, MSc, Neuroradiologist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** In developed countries, stroke is the third leading cause of death and the leading cause of permanent disability. Systemic and endovascular thrombolytic treatments in acute cerebral ischemic stroke caused by occlusion of large caliber vessels are currently the standard of care for the acute treatment of stroke. The rationale of this study is to validate the results of this treatment on a large scale, in the context of what can be called "real life". The study will have the characteristics of a descriptive observational study on patients suffering from acute ischemic stroke treated at the Policlinico A. Gemelli-IRCCS from 1 January 2016 to 31 December 2023. These data will be compared with a retrospective control group of patients undergoing mechanical thrombectomy for cerebral ischemic stroke in our polyclinic. The primary endpoint is the outcome of patients treated with mechanical endovascular thrombectomy evaluated with the modified Ranking Scale at 90 days, while as secondary endpoints some individual characteristics of the patient will be considered (sex, age, clinical history, etc.), characteristics of the thrombus (anatomical-pathological, radiological etc) and related to acute management (therapy, rehabilitation, etc). **Detailed Description:** Background and rationale of the study In developed countries, stroke is the third leading cause of death and the leading cause of permanent disability. Recently, while some developments have been observed in the acute treatment of ischemic stroke such as the introduction of thrombolysis with rt-PA in the acute phase, in the face of acceptable side effects (NINDS, SITS MOST, ECASS), new treatments have been approved for the acute treatment of some types of acute stroke, such as endovascular treatment. Endovascular treatment in acute cerebral ischemic stroke caused by large vessel occlusion has become the standard of care following the publication of five multicenter randomized trials performed in different reference centers in 2015. In these studies, the treatment cut-off was set at 4.5 hours, a previously validated standard time for intravenous thrombolysis, only for one of these was it instead set at 6 hours. In 2018, two other trials were published, which demonstrated the efficacy of the treatment even beyond 6 hours, one 16 hours after onset, the other up to 24 hours. Several case studies have now been published which confirm the results of these latest trials, and others which demonstrate how the indications can be extended even beyond those envisaged by the most recent international guidelines. The development of this therapeutic approach has therefore upset what was the standard therapy and consequently the natural history of many patients suffering from cerebral ischemic stroke. The rationale of this study is to validate the results of this treatment on a large scale, in the context of what can be called "real life" (outside a randomized multicenter trial), as well as to define more precisely indications, contraindications , benefits (outcome at 90 days measured with the modified Ranking Scale) and possible complications of this technique. Furthermore, the presence of cofactors relating to acute management, thrombus characteristics and the data emerging from neuro-imaging performed in the acute phase that can determine better results will be evaluated. Working hypothesis: in the various trials reported, divergences emerge in terms of characteristics of the patients enrolled, treatment timing and patient management in the acute phase. The hypothesis is that some characteristics of the patient, of the thrombus or of the type of treatment are important for the success of the treatment and their identification would allow to individualize the treatment determining better outcomes. ### Conditions Module **Conditions:** - Stroke - Endovascular Thrombectomy - Ischemic Stroke ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** OTHER #### Enrollment Info **Count:** 600 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Months ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** An endovascular thrombectomy is the removal of a thrombus (blood clot) under image guidance. A thrombectomy is most commonly performed for an arterial embolism, which is an arterial blockage often caused by atrial fibrillation, a heart rhythm disorder. **Name:** Endovascular thrombectomy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** outcome of patients treated by mechanical endovascular thrombectomy evaluated with modified Ranking Scale at 90 days. **Measure:** 3 months mRS **Time Frame:** 3 months #### Secondary Outcomes **Description:** Correlation between radiological parameters (site of occlusion, ASPECT score on CT without contrast medium, angiographic mTICI at the end of the procedure) and clinical parameters (age, NIHSS at onset) with outcome at 90 days. **Measure:** Radiological-clinical correlation **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * age \> 18 years * Acute ischemic stroke with consistent neurologic and radiologic evidence. * Performing a CT without contrast and a triphasic CT angiography. * Execution of mechanical endovascular thrombectomy procedure (whose indication is placed by a neurologist and interventional neuroradiologist). Exclusion Criteria: * patients lost to follow-up (e.g. back-transfer). **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Descriptive observational study on patients with acute ischemic stroke treated at the Policlinico A. Gemelli- IRCCS from 1 January 2016 to 31 December 2023. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** andrea.alexandre@policlinicogemelli.it **Name:** Andrea M Alexandre, MD, MSc **Phone:** +390630151 **Role:** CONTACT #### Locations **Location 1:** **City:** Roma **Contacts:** ***Contact 1:*** - **Email:** andrea.alexandre@policlinicogemelli.it - **Name:** Andrea M Alexandre, MD, MSc - **Phone:** +390630151 - **Role:** CONTACT **Country:** Italy **Facility:** Fondazione Policlinico Universitario A.Gemelli IRCCS **State:** RM **Status:** RECRUITING **Zip:** 00168 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Alexandre AM, Pedicelli A, Valente I, Scarcia L, Giubbolini F, D'Argento F, Lozupone E, Distefano M, Pilato F, Colosimo C. May endovascular thrombectomy without CT perfusion improve clinical outcome? Clin Neurol Neurosurg. 2020 Nov;198:106207. doi: 10.1016/j.clineuro.2020.106207. Epub 2020 Sep 7. **PMID:** 32950754 **Citation:** Alexandre AM, Valente I, Consoli A, Piano M, Renieri L, Gabrieli JD, Russo R, Caragliano AA, Ruggiero M, Saletti A, Lazzarotti GA, Pileggi M, Limbucci N, Cosottini M, Cervo A, Viaro F, Vinci SL, Commodaro C, Pilato F, Pedicelli A. Posterior Circulation Endovascular Thrombectomy for Large-Vessel Occlusion: Predictors of Favorable Clinical Outcome and Analysis of First-Pass Effect. AJNR Am J Neuroradiol. 2021 May;42(5):896-903. doi: 10.3174/ajnr.A7023. Epub 2021 Mar 4. **PMID:** 33664106 **Citation:** Alexandre AM, Valente I, Frisullo G, Morosetti R, Genovese D, Bartolo A, Gigli R, Rollo C, Scarcia L, Carosi F, Fortunato G, D'Argento F, Calabresi P, Della Marca G, Pedicelli A, Broccolini A. Mechanical thrombectomy in patients with stroke due to large vessel occlusion in the anterior circulation and low baseline NIHSS score. J Integr Neurosci. 2021 Sep 30;20(3):645-650. doi: 10.31083/j.jin2003068. **PMID:** 34645097 **Citation:** Pilato F, Silva S, Valente I, Distefano M, Broccolini A, Brunetti V, Caliandro P, Marca GD, Di Iorio R, Frisullo G, Monforte M, Morosetti R, Piano C, Calandrelli R, Capone F, Alexandre A, Pedicelli A, Colosimo C, Caricato A. Predicting Factors of Functional Outcome in Patients with Acute Ischemic Stroke Admitted to Neuro-Intensive Care Unit-A Prospective Cohort Study. Brain Sci. 2020 Nov 26;10(12):911. doi: 10.3390/brainsci10120911. **PMID:** 33256264 **Citation:** Di Iorio R, Pilato F, Valente I, Laurienzo A, Gaudino S, Frisullo G, Profice P, Cottonaro S, Alexandre A, Caliandro P, Morosetti R, Lozupone E, D'Argento F, Pedicelli A, Colosimo C, Calabresi P, Della Marca G, Broccolini A. Role of Favorable Perfusion Imaging in Predicting the Outcome of Patients with Acute Ischemic Stroke due to Large Vessel Occlusion Undergoing Effective Thrombectomy: A Single-Center Study. Cerebrovasc Dis Extra. 2021;11(1):1-8. doi: 10.1159/000513025. Epub 2021 Jan 15. **PMID:** 33454704 **Citation:** Alexandre AM, Valente I, Consoli A, Trombatore P, Scarcia L, Piano M, Limbucci N, Gabrieli JD, Russo R, Caragliano AA, Ruggiero M, Saletti A, Lazzarotti GA, Pileggi M, Cosottini M, Pilato F, Slomka A, Colo F, Giubbolini F, Frisullo G, Della Marca G, Broccolini A, Pedicelli A. Posterior Circulation Endovascular Thrombectomy for Large Vessels Occlusion in Patients Presenting with NIHSS Score </= 10. Life (Basel). 2021 Dec 17;11(12):1423. doi: 10.3390/life11121423. **PMID:** 34947955 **Citation:** Alexandre AM, Colo F, Brunetti V, Valente I, Frisullo G, Pedicelli A, Scarcia L, Rollo C, Falcou A, Milonia L, Andrighetti M, Piano M, Macera A, Commodaro C, Ruggiero M, Da Ros V, Bellini L, Lazzarotti GA, Cosottini M, Caragliano AA, Vinci SL, Gabrieli JD, Causin F, Panni P, Roveri L, Limbucci N, Arba F, Pileggi M, Bianco G, Romano DG, Diana F, Semeraro V, Burdi N, Ganimede MP, Lozupone E, Fasano A, Lafe E, Cavallini A, Russo R, Bergui M, Calabresi P, Della Marca G, Broccolini A. Mechanical thrombectomy in minor stroke due to isolated M2 occlusion: a multicenter retrospective matched analysis. J Neurointerv Surg. 2023 Nov;15(e2):e198-e203. doi: 10.1136/jnis-2022-019557. Epub 2022 Oct 12. **PMID:** 36223995 **Citation:** Pilato F, Valente I, Calandrelli R, Alexandre A, Arena V, Dell'Aquila M, Broccolini A, Della Marca G, Morosetti R, Frisullo G, Brunetti V, Distefano M, Pedicelli A, Colosimo C, Di Lazzaro V. Clot evaluation and distal embolization risk during mechanical thrombectomy in anterior circulation stroke. J Neurol Sci. 2022 Jan 15;432:120087. doi: 10.1016/j.jns.2021.120087. Epub 2021 Dec 14. **PMID:** 34933250 **Citation:** Alexandre AM, Valente I, Pedicelli A, Pezzullo AM, Colo F, Scarcia L, Romi A, Piano M, Macera A, Gabrieli JD, Cester G, Caragliano AA, Vinci SL, Ruggiero M, Commodaro C, Saletti A, Lazzarotti GA, Cosottini M, Da Ros V, Bellini L, Lozupone E, Paladini A, Brunetti V, Morosetti R, Frisullo G, Calabresi P, Marca GD, Broccolini A. Mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in the anterior circulation and low baseline National Institute of Health Stroke Scale score: a multicenter retrospective matched analysis. Neurol Sci. 2022 May;43(5):3105-3112. doi: 10.1007/s10072-021-05771-5. Epub 2021 Nov 29. **PMID:** 34843020 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes - ID: D000020520 - Term: Brain Infarction - ID: D000002545 - Term: Brain Ischemia - ID: D000007238 - Term: Infarction - ID: D000009336 - Term: Necrosis ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10543 - Name: Ischemia - Relevance: HIGH - As Found: Ischemic - ID: M22306 - Name: Stroke - Relevance: HIGH - As Found: Stroke - ID: M2400 - Name: Ischemic Stroke - Relevance: HIGH - As Found: Ischemic Stroke - ID: M5793 - Name: Cerebral Infarction - Relevance: HIGH - As Found: Ischemic Stroke - ID: M10282 - Name: Infarction - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M22305 - Name: Brain Infarction - Relevance: LOW - As Found: Unknown - ID: M5794 - Name: Brain Ischemia - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000020521 - Term: Stroke - ID: D000083242 - Term: Ischemic Stroke - ID: D000002544 - Term: Cerebral Infarction - ID: D000007511 - Term: Ischemia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05909579 **Brief Title:** Investigating the Effectiveness of PelvicSense(R) on Pain and Sexual Outcomes in Endometriosis **Official Title:** Investigating the Effectiveness of PelvicSense(R) on Pain and Sexual Outcomes in Endometriosis #### Organization Study ID Info **ID:** 379631-2 #### Organization **Class:** OTHER **Full Name:** Queen's University ### Status Module #### Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-16 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-14 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Start Date **Date:** 2023-11-02 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2023-06-18 **Type:** ACTUAL **Study First Submit Date:** 2023-05-05 **Study First Submit QC Date:** 2023-06-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dr. Caroline Pukall #### Responsible Party **Investigator Affiliation:** Queen's University **Investigator Full Name:** Dr. Caroline Pukall **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will examine the effectiveness of the PelvicSense 3-month online program on pain and other outcomes in those with endometriosis. This study is prospective in nature and will involve several assessment points: baseline, immediately post-treatment (at the end of the 3 month program), and 3-month follow up. All aspects of the study will be conducted remotely (e.g., online, email, video calls), and participants will be at least 18 years of age, fluent in English, and experience pain due to endometriosis for at least 3 months with a physician diagnosis. Participants are expected to continue their treatment as usual and this information will be documented throughout the study. ### Conditions Module **Conditions:** - Endometriosis ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** PelvicSense® is a home-based physiotherapy program integrating multiple techniques, including relaxation, breathing, stretching, strengthening and at-home manual therapy. This program also educates participants about the anatomy and physiology of the pelvis and teaches strategies to strengthen the mind-muscle connection to the pelvis. **Intervention Names:** - Behavioral: PelvicSense (R) **Label:** 3 month PelvicSense(R) program **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 3 month PelvicSense(R) program **Description:** PelvicSense® is a home-based physiotherapy program integrating multiple techniques, including relaxation, breathing, stretching, strengthening and at-home manual therapy. This program also educates participants about the anatomy and physiology of the pelvis and teaches strategies to strengthen the mind-muscle connection to the pelvis. **Name:** PelvicSense (R) **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Sexual Distress Scale, Short Form (SDS-SF). 5 items rated on 5 point scales from 0 (never) to 4 (always). Total scores range from 0-20. Higher scores are worse. **Measure:** Sexual distress **Time Frame:** Baseline **Description:** Sexual Distress Scale, Short Form (SDS-SF). 5 items rated on 5 point scales from 0 (never) to 4 (always). Total scores range from 0-20. Higher scores are worse. **Measure:** Sexual distress **Time Frame:** At the end of the 3 month program **Description:** Sexual Distress Scale, Short Form (SDS-SF). 5 items rated on 5 point scales from 0 (never) to 4 (always). Total scores range from 0-20. Higher scores are worse. **Measure:** Sexual distress **Time Frame:** 3 months after the end of the program **Description:** Pain Self-Efficacy Questionnaire (PSEQ). 10 items rated on 7 point scales from 0 (not at all confident) to 6 (completely confident). Total scores range from 0-60. **Measure:** Pain self-efficacy **Time Frame:** Baseline **Description:** Pain Self-Efficacy Questionnaire (PSEQ). 10 items rated on 7 point scales from 0 (not at all confident) to 6 (completely confident). Total scores range from 0-60. **Measure:** Pain self-efficacy **Time Frame:** At the end of the 3 month program **Description:** Pain Self-Efficacy Questionnaire (PSEQ). 10 items rated on 7 point scales from 0 (not at all confident) to 6 (completely confident). Total scores range from 0-60. **Measure:** Pain self-efficacy **Time Frame:** 3 months after the end of the program #### Primary Outcomes **Description:** Pain Intensity Numerical Rating Scale (NRS). Participants will be asked to report their pain intensity on an 11-point numerical scale of 0 (no pain) to 10 (worst pain ever felt). **Measure:** Pain intensity **Time Frame:** Baseline **Description:** Pain Intensity Numerical Rating Scale (NRS). Participants will be asked to report their pain intensity on an 11-point numerical scale of 0 (no pain) to 10 (worst pain ever felt). **Measure:** Pain intensity **Time Frame:** At the end of the 3 month program **Description:** Pain Intensity Numerical Rating Scale (NRS). Participants will be asked to report their pain intensity on an 11-point numerical scale of 0 (no pain) to 10 (worst pain ever felt). **Measure:** Pain intensity **Time Frame:** 3 months after the end of the program #### Secondary Outcomes **Description:** Pain Catastrophizing Scale (PCS). 13 items rated on 5 point scales from 0 (not at all) to 4 (all the time). Total scores range from 0-52. Higher scores are worse. **Measure:** Pain catastrophizing **Time Frame:** Baseline **Description:** Pain Catastrophizing Scale (PCS). 13 items rated on 5 point scales from 0 (not at all) to 4 (all the time). Total scores range from 0-52. Higher scores are worse. **Measure:** Pain catastrophizing **Time Frame:** At the end of the 3 month program **Description:** Pain Catastrophizing Scale (PCS). 13 items rated on 5 point scales from 0 (not at all) to 4 (all the time). Total scores range from 0-52. Higher scores are worse. **Measure:** Pain catastrophizing **Time Frame:** 3 months after the end of the program ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18 years or older, fluent in English, and have a formal diagnosis of endometriosis for at least 3 months. Exclusion Criteria: * Younger than 18 years of age, nonfluency in English, self-identified diagnosis, endometriosis duration of less than 3 months. **Gender Based:** True **Gender Description:** All identities accepted with female pelvic anatomy. **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** caroline.pukall@queensu.ca **Name:** Caroline Pukall, PhD **Phone:** 613 533 3200 **Role:** CONTACT #### Locations **Location 1:** **City:** Kingston **Contacts:** ***Contact 1:*** - **Email:** caroline.pukall@queensu.ca - **Name:** Caroline Pukall, PhD - **Phone:** 613 533 3200 - **Role:** CONTACT ***Contact 2:*** - **Email:** shannon.coyle13@gmail.com - **Name:** Shannon Coyle, MA - **Phone:** 613 533 3276 - **Role:** CONTACT **Country:** Canada **Facility:** Sexual Health Research Laboratory, Department of Psychology, Queen's University **State:** Ontario **Status:** RECRUITING **Zip:** K7L 3N6 #### Overall Officials **Official 1:** **Affiliation:** Queen's University **Name:** Caroline Pukall, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Please email the PI at caroline.pukall@queensu.ca **Description:** De-identified data will be available to other researchers after publication of the results. **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** De-identified data will be available to other researchers for 2 years after publication of the results. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M7877 - Name: Endometriosis - Relevance: HIGH - As Found: Endometriosis - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004715 - Term: Endometriosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00626379 **Acronym:** CHAS **Brief Title:** Examining How Heart Disease Risk Factors Affect Healthy Aging (The Chicago Healthy Aging Study [CHAS]) **Official Title:** Low CV Risk, Ages 25-44 & CV/Non-CV Outcomes, Ages 65+ #### Organization Study ID Info **ID:** 1379 #### Organization **Class:** OTHER **Full Name:** Northwestern University #### Secondary ID Infos **ID:** R01HL081141-04 **Link:** https://reporter.nih.gov/quickSearch/R01HL081141-04 **Type:** NIH ### Status Module #### Completion Date **Date:** 2010-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-08 **Type:** ACTUAL #### Start Date **Date:** 2007-11 **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2008-02-29 **Type:** ESTIMATED **Study First Submit Date:** 2008-02-27 **Study First Submit QC Date:** 2008-02-27 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Heart, Lung, and Blood Institute (NHLBI) #### Lead Sponsor **Class:** OTHER **Name:** Northwestern University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Heart disease is the leading cause of death in the United States and is responsible for 30% of all deaths in the United States. This study will examine how risk factors for heart disease in young and middle aged people affect people's health as they grow older. **Detailed Description:** Heart disease, including coronary heart disease (CHD) and cardiovascular disease (CVD), is a serious health problem in the United States. It is the leading cause of death in this country, and each year almost 700,000 people die from the disease. Risk factors for heart disease include high blood pressure, high cholesterol levels, tobacco use, diabetes, and history of a prior heart attack. It has been shown that young and middle aged adults with few risk factors experience a lower incidence of heart disease, lower Medicare costs, and longer lives than those with more risk factors. However, it is not known how having a low risk for heart disease at a young age affects health-related outcomes in older age. It may be possible that a low risk for developing heart disease in younger years results in healthier aging than does a higher risk. This study will examine former participants of the Chicago Heart Association (CHA) study who are now 65 to 84 years old. The purpose of this study is to determine how risk factors for heart disease in young adulthood and middle age are related to healthy aging. This study will enroll 1500 people who participated in the CHA study from 1967 to 1973 and who are still living in the Greater Chicagoland area. Six hundred former participants who had a low risk of developing heart disease and 900 former participants who had a high risk of developing heart disease will be enrolled. Participants will attend one study visit that will include medical history interviews and questionnaires, a physical examination, blood pressure measurements, blood and urine collection, and an electrocardiogram (ECG) to measure the electrical activity of the heart. Blood samples will be collected and stored for future genetic testing. Participants will undergo physical functioning performance tests on balance, leg strength and coordination, grip strength, and endurance. They will also undergo a computed tomography chest scan to measure the amount of calcium in the arteries of the heart and ultrasound scans of the arteries in the neck to measure artery size and function. ### Conditions Module **Conditions:** - Coronary Disease - Cardiovascular Diseases **Keywords:** - Coronary Heart Disease - Subclinical Atherosclerosis - CVD-Related Markers of Inflammation - Mortality ### Design Module #### Bio Spec **Description:** Whole blood, serum, white cells, and urine **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 1395 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Measure:** Subclinical atherosclerosis, CVD-related markers of inflammation, and levels of physical performance **Time Frame:** Measured during participant's one (baseline) study visit ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participated in the CHA study * Lives in the Greater Chicagoland area Exclusion Criteria: * Severely ill, disabled, or cognitively impaired **Maximum Age:** 84 Years **Minimum Age:** 65 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - OLDER_ADULT **Study Population:** Original participants in the Chicago Heart Association (CHA) Detection in Industry study (1967 to 1973) who still reside in the Greater Chicagoland area. ### Contacts Locations Module #### Locations **Location 1:** **City:** Chicago **Country:** United States **Facility:** Preventive Medicine Research Clinic **State:** Illinois **Zip:** 60611 #### Overall Officials **Official 1:** **Affiliation:** Northwestern University Feinberg School of Medicine **Name:** Martha L. Daviglus, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** No plan to share. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000017202 - Term: Myocardial Ischemia - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M6549 - Name: Coronary Disease - Relevance: HIGH - As Found: Coronary Disease - ID: M6546 - Name: Coronary Artery Disease - Relevance: LOW - As Found: Unknown - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M26188 - Name: Atherosclerosis - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000003327 - Term: Coronary Disease ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03530579 **Acronym:** RICE **Brief Title:** Community Health Worker Diabetes Prevention Intervention **Official Title:** Community Health Worker Diabetes Prevention Intervention #### Organization Study ID Info **ID:** 11-01416 #### Organization **Class:** OTHER **Full Name:** NYU Langone Health ### Status Module #### Completion Date **Date:** 2015-02-13 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-05-21 **Type:** ACTUAL **Last Update Submit Date:** 2018-05-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-02-13 **Type:** ACTUAL #### Start Date **Date:** 2014-02-13 **Type:** ACTUAL **Status Verified Date:** 2018-05 #### Study First Post Date **Date:** 2018-05-21 **Type:** ACTUAL **Study First Submit Date:** 2018-05-08 **Study First Submit QC Date:** 2018-05-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** NYU Langone Health #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary goal of this study is to develop, implement, and test a community health worker (CHW) program designed to promote diabetes prevention among Korean and South Asian Americans in New York City. In particular, the specific aims of this study are: 1. To utilize community based participatory research (CBPR) methods to expand upon an existing campus-community partnership to develop and implement a CHW program among Korean and South Asian Americans that promotes diabetes prevention; 2. To develop, implement, and assess the efficacy of a CHW intervention to promote diabetes prevention and access to care among NYC Koreans and South Asians. ### Conditions Module **Conditions:** - Diabetes Prevention **Keywords:** - Diabetes Prevention ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 954 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive 6 two and a half hour educational group trainings over the course of 6 months. **Intervention Names:** - Behavioral: Educational group trainings **Label:** Group 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** A community health worker will answer your questions about diabetes and refer participant if you need one. **Intervention Names:** - Behavioral: Community Health Care Worker **Label:** Group 2 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1 **Description:** Participants will receive 6 two and a half hour educational group training's over the course of 6 months. These sessions will be led by a trained CHW in your language and will be held on a monthly basis in a community based location. Session 1: What is Diabetes * Why is Prevention Important Session 2: Nutrition Session 3: Physical Activity Session 4: Cardiovascular Disease \& Diabetes Complication Session 5: Stress Management Session 6: Access to Service **Name:** Educational group trainings **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Group 2 **Description:** A community health care worker answer your questions about diabetes and refer participant to a physician. Survey will be completed at the start of the study and during the 3rd, 6th and 12th months **Name:** Community Health Care Worker **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** Change in weight **Time Frame:** 3 Months, 6 Months, 12 Months **Measure:** Change in Body Mass Index **Time Frame:** 3 Months, 6 Months, 12 Months **Measure:** Change in hip-to-waist ratio measurements **Time Frame:** 3 Months, 6 Months, 12 Months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * is a South Asian or Korean American immigrant; * is identified as at-risk by a diabetes risk assessment * is between 18-75 years of age; and * is willing to be randomized to either treatment or control groups. Exclusion Criteria: * is a confirmed diabetic; * is on renal dialysis; * has an acute or terminal illness or serious mental illness; * has a history of recent coronary event within the last 12 months; * has a recent history of acute medical problem or admission to hospital; * has any other severe medical conditions that might make it difficult to attend educational sessions; * has poor short-term prognosis (expected death in \<2 years); * is planning to travel for longer than 6 weeks during the 6-month intervention period; or * is participating in another CVD study. **Healthy Volunteers:** True **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** NYU Langone Health **Name:** Nadia Islam, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Wyatt LC, Katigbak C, Riley L, Zanowiak JM, Ursua R, Kwon SC, Trinh-Shevrin C, Islam NS. Promoting Physical Activity Among Immigrant Asian Americans: Results from Four Community Health Worker Studies. J Immigr Minor Health. 2023 Apr;25(2):291-305. doi: 10.1007/s10903-022-01411-y. Epub 2022 Oct 23. **PMID:** 36273386 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00943579 **Brief Title:** Open-Label Extension Study of Kuvan for Autism **Official Title:** Kuvan® (Sapropterin) as a Treatment for Autistic Disorder: An Open Label Extension Protocol #### Organization Study ID Info **ID:** CHC-0902 #### Organization **Class:** OTHER **Full Name:** The Children's Health Council ### Status Module #### Completion Date **Date:** 2012-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-05-02 **Type:** ACTUAL **Last Update Submit Date:** 2018-04-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2013-07-04 **Type:** ESTIMATED **Results First Submit Date:** 2013-01-16 **Results First Submit QC Date:** 2013-07-02 #### Start Date **Date:** 2009-08 **Status Verified Date:** 2018-04 #### Study First Post Date **Date:** 2009-07-22 **Type:** ESTIMATED **Study First Submit Date:** 2009-07-20 **Study First Submit QC Date:** 2009-07-20 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** BioMarin Pharmaceutical #### Lead Sponsor **Class:** OTHER **Name:** The Children's Health Council #### Responsible Party **Investigator Affiliation:** The Children's Health Council **Investigator Full Name:** Glen R. Elliott **Investigator Title:** Chief Psychiatrist and Medical Director **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an open-label extension study available only to subjects who completed an earlier double-blind, placebo-controlled study of sapropterin in children with autism. **Detailed Description:** This is an open-label extension study available only to subjects who completed an earlier double-blind, placebo-controlled study of sapropterin in children with autism. During this protocol, all subjects will be receiving brand-name Kuvan 20 mg/kg/day for 16 weeks; subject who complete the first 16 weeks will have the option of continuing on Kuvan at the same dose for up to 90 days after the last subject has completed the first 16 weeks of this protocol. The purpose of the study primarily is to gather additional information on safety and efficacy in this population. ### Conditions Module **Conditions:** - Autistic Disorder **Keywords:** - autism - autistic disorder - tetrahydrobiopterin - sapropterin - treatment ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 41 **Type:** ACTUAL **Phases:** - PHASE2 - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. **Intervention Names:** - Drug: Kuvan® **Label:** Kuvan® **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Kuvan® **Description:** Brand-name Kuvan® (sapropterin) will be administered to all subjects at a dose of 20 mg/kg/day for 16 weeks. **Name:** Kuvan® **Other Names:** - sapropterin - tetrahydrobiopterin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** This is a summary judgment made by a trained clinician based on observed and reported behaviors of the child compared to baseline. It is a 7-point scale (1) very much improved, (2) much improved, (3) minimally improved (4) no change, (5) minimally worse, (6) much worse and (7) very much worse. Chi-square analyses were used to assess change in CHI-I scores (by group, post-test)Mixed-effects regression models determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. The mixed-effects regression model is robust to data dependency that occurs with the repeated assessments of individuals over time \& can handle missing data. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time **Measure:** Clinical Global Impressions Scale **Time Frame:** 16 weeks #### Secondary Outcomes **Description:** The Vineland-2 is semi-structured interview designed to communication, daily living, socialization and motor skills. The Vineland-2 is comprised of a total Adaptive Composite Scale; we chose to use 10 subscales that specifically address functional domains relevant for a young ASD sample - Receptive Communication, Expressive Communication, Personal Daily Living Skills, Domestic Daily Living Skills, Community Daily Living Skills, Interpersonal Relations, Play Skills, Coping Skills, Gross Motor Skills, Fine Motor Skills. The scales generate raw or sum, V-, and age-equivalent scores; raw scores were selected for use in this study. Higher subscale scores indicate more skills. Raw scores can range from 0 to 766 for the overall adaptive behavior composite. Subscales are combined to form the overall Adaptive Behavior Composite, which is essentially a weighted average of the various subscales combined. **Measure:** Vineland Adaptive Behavior Scale, 2nd Edition **Time Frame:** Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). **Description:** The C-YBOCS is a scale is designed to rate the severity of obsessive and compulsive symptoms in children and adolescents, ages 6 to 17 years. It can be administered by a clinican or trained interviewer in a semi-structured fashion. In general, the ratings depend on the child's and parent's report; however, the final rating is based on the clinical judgement of the interviewer. Rate the characteristics of each item over the prior week up until, and including, the time of the interview. Scores should reflect the average of each item for the entire week, unless otherwise specified. **Measure:** Children's Yale Brown Obsessive Compulsive Scale **Time Frame:** Weeks 8 & 16 **Description:** this is a measure of parents impression of improvement. **Measure:** Parental Global Assessment **Time Frame:** Weeks 8 & 16 **Description:** Measures expressive \& receptive language and total scores in ages 0 to 6 years 11 months. The scales generate raw, standard, and age-equivalent scores; raw scores for the total scale were selected for use in this study. Total is average of subscales. Minimum raw score = 0, maximum = 130. Higher raw scores indicate better language skills. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept \& trend modeling that accounts for each individual's initial level of symptom severity/functioning \& rate of change/time **Measure:** Preschool Language Scale, 4th Edition (PLS-4) **Time Frame:** Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). **Description:** This is a measure of behavioral symptomatology in children 2-6 years of age. The ADHD scale is one subdomain. **Measure:** Connor's Preschool ADHD Questionnaire **Time Frame:** Weeks 8 & 16 **Description:** This is a 58-item informant-based, factor-analyzed scale comprised of a total scale and 5 subscales that generate raw scores. Scores based on a likert scale ranging from 0-3 where 0 is not a problem to 3 where the problem is severe. Subscales include: Irritability, Social Withdrawal, Stereotypic Behaviors, Hyperactivity and Inappropriate Speech. Total maximum score is 174. Higher subscale scores indicate more symptoms. Scores are totaled to compute subscale scores. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time **Measure:** Aberrant Behavior Checklist (ABC) **Time Frame:** Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). **Description:** This is not a standardized measure but instead a set of questions, both closed and open ended, asked of families about their child's response to the medication. Used for determining whether treatment needed to be discontinued. **Measure:** Adverse Events Reporting **Time Frame:** Cummulative throughout study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All subjects must have completed earlier trial, CHC 0901 (NCT00850070) * Parents must be willing and able to sign informed consent Exclusion Criteria: * Child failed to complete CHC 0901 (NCT00850070) **Maximum Age:** 6 Years **Minimum Age:** 3 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Palo Alto **Country:** United States **Facility:** The Children's Health Council **State:** California **Zip:** 94304 #### Overall Officials **Official 1:** **Affiliation:** The Children's Health Council **Name:** Glen R Elliott, PhD, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000067877 - Term: Autism Spectrum Disorder - ID: D000002659 - Term: Child Development Disorders, Pervasive - ID: D000065886 - Term: Neurodevelopmental Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4623 - Name: Autistic Disorder - Relevance: HIGH - As Found: Autistic Disorder - ID: M206 - Name: Autism Spectrum Disorder - Relevance: LOW - As Found: Unknown - ID: M5903 - Name: Child Development Disorders, Pervasive - Relevance: LOW - As Found: Unknown - ID: M5902 - Name: Developmental Disabilities - Relevance: LOW - As Found: Unknown - ID: M30644 - Name: Neurodevelopmental Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001321 - Term: Autistic Disorder ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** All participants were asked at each visit regarding adverse events. Specific examples were asked, such as difficulties with sleep, irritability and bowel movements then it was left open ended for parents to describe if other adverse events were noted. #### Event Groups **Group ID:** EG000 **Title:** Kuvan Following Placebo **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** EG000 **Other Num Affected:** 14 **Other Num at Risk:** 21 **Serious Number At Risk:** 21 **Title:** Kuvan Following Placebo **Group ID:** EG001 **Title:** Kuvan Following Active Treatment **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** EG001 **Other Num Affected:** 13 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Kuvan Following Active Treatment **Frequency Threshold:** 1 #### Other Events **Term:** Changes in bowel movements **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Diarrhea **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Increased irritability in a variety of settings **Organ System:** Psychiatric disorders **Source Vocabulary:** **Term:** Difficulty Sleeping **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Persistent changes in sleep, including onset insomnia, frequent wakening during the night, lightening of sleep **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Viral or autoimmune rash **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Hyperactivity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Persistent increase in overall activity level in a variety of settings **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Increase in anxious symptoms **Organ System:** Psychiatric disorders **Source Vocabulary:** **Term:** Repetitive Behaviors **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Sustained changes in or appearance of stereotypies or other odd, repetitive behaviors **Organ System:** Nervous system disorders **Source Vocabulary:** **Time Frame:** Adverse events were monitored for the length of the study, i.e., 16 weeks. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 41 **Units:** Participants ### Group **ID:** BG000 **Title:** Kuvan Following Placebo **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. ### Group **ID:** BG001 **Title:** Kuvan Following Active Treatment **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 21 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 41 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1 **Value:** 5 #### Measurement **Group ID:** BG001 **Spread:** 1 **Value:** 5 #### Measurement **Group ID:** BG002 **Spread:** 1 **Value:** 5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 10 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 16 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 31 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 21 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 41 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** gelliott@chconline.org **Organization:** Children's Health Council **Phone:** 650.688.3649 **Title:** Glen R. Elliott, Ph.D., MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** 95 **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Chi-square analyses were used to assess CGI-I scores. there were no transformations. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** >.05 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Chi-squared **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.77 - **Upper Limit:** - **Value:** 275 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.78 - **Upper Limit:** - **Value:** 321 **Title:** #### Outcome Measure 3 #### Outcome Measure 4 #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.48 - **Upper Limit:** - **Value:** 57.24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.27 - **Upper Limit:** - **Value:** 77.83 **Title:** #### Outcome Measure 6 #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.68 - **Upper Limit:** - **Value:** 16.84 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.73 - **Upper Limit:** - **Value:** 9.70 **Title:** #### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** This is a summary judgment made by a trained clinician based on observed and reported behaviors of the child compared to baseline. It is a 7-point scale (1) very much improved, (2) much improved, (3) minimally improved (4) no change, (5) minimally worse, (6) much worse and (7) very much worse. Chi-square analyses were used to assess change in CHI-I scores (by group, post-test)Mixed-effects regression models determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. The mixed-effects regression model is robust to data dependency that occurs with the repeated assessments of individuals over time \& can handle missing data. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time **Parameter Type:** NUMBER **Population Description:** The number of participants analyzed included those who completed the open label extension of this study. **Reporting Status:** POSTED **Time Frame:** 16 weeks **Title:** Clinical Global Impressions Scale **Type:** PRIMARY **Unit of Measure:** # participants much - very much improved ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** OG001 **Title:** Kuvan Following Active Treatment #### Outcome Measure 2 **Description:** The Vineland-2 is semi-structured interview designed to communication, daily living, socialization and motor skills. The Vineland-2 is comprised of a total Adaptive Composite Scale; we chose to use 10 subscales that specifically address functional domains relevant for a young ASD sample - Receptive Communication, Expressive Communication, Personal Daily Living Skills, Domestic Daily Living Skills, Community Daily Living Skills, Interpersonal Relations, Play Skills, Coping Skills, Gross Motor Skills, Fine Motor Skills. The scales generate raw or sum, V-, and age-equivalent scores; raw scores were selected for use in this study. Higher subscale scores indicate more skills. Raw scores can range from 0 to 766 for the overall adaptive behavior composite. Subscales are combined to form the overall Adaptive Behavior Composite, which is essentially a weighted average of the various subscales combined. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All participants who completed the open label extension were analyzed. **Reporting Status:** POSTED **Time Frame:** Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). **Title:** Vineland Adaptive Behavior Scale, 2nd Edition **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **ID:** OG001 **Title:** Kuvan Following Active Treatment #### Outcome Measure 3 **Description:** The C-YBOCS is a scale is designed to rate the severity of obsessive and compulsive symptoms in children and adolescents, ages 6 to 17 years. It can be administered by a clinican or trained interviewer in a semi-structured fashion. In general, the ratings depend on the child's and parent's report; however, the final rating is based on the clinical judgement of the interviewer. Rate the characteristics of each item over the prior week up until, and including, the time of the interview. Scores should reflect the average of each item for the entire week, unless otherwise specified. **Population Description:** The data was not analyzed secondary to lack of significant findings in primary outcome measures and limited data collected on this measure. The data cannot now be provided as the research team has since disbanded and it is not possible to reanalyze the data at this time. **Reporting Status:** POSTED **Time Frame:** Weeks 8 & 16 **Title:** Children's Yale Brown Obsessive Compulsive Scale **Type:** SECONDARY ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Kuvan®: Brand-name Kuvan® (sapropterin) will be administered to all subjects at a dose of 20 mg/kg/day for 16 weeks. **ID:** OG000 **Title:** Kuvan® #### Outcome Measure 4 **Description:** this is a measure of parents impression of improvement. **Population Description:** the data were not analyzed secondary to lack of findings in primary outcome measure as well as the nature of an open label study. The data cannot now be provided as the research team has since disbanded and it is not possible to reanalyze the data at this time. **Reporting Status:** POSTED **Time Frame:** Weeks 8 & 16 **Title:** Parental Global Assessment **Type:** SECONDARY ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** OG001 **Title:** Kuvan Following Active Treatment #### Outcome Measure 5 **Description:** Measures expressive \& receptive language and total scores in ages 0 to 6 years 11 months. The scales generate raw, standard, and age-equivalent scores; raw scores for the total scale were selected for use in this study. Total is average of subscales. Minimum raw score = 0, maximum = 130. Higher raw scores indicate better language skills. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept \& trend modeling that accounts for each individual's initial level of symptom severity/functioning \& rate of change/time **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All participants completed the open label extension were analyzed in the study. **Reporting Status:** POSTED **Time Frame:** Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). **Title:** Preschool Language Scale, 4th Edition (PLS-4) **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** OG001 **Title:** Kuvan Following Active Treatment #### Outcome Measure 6 **Description:** This is a measure of behavioral symptomatology in children 2-6 years of age. The ADHD scale is one subdomain. **Population Description:** Data was not analyzed secondary to lack of significant findings in primary outcome measure and reduced number of completed questionnaires. The data cannot now be provided as the research team has since disbanded and it is not possible to reanalyze the data at this time. **Reporting Status:** POSTED **Time Frame:** Weeks 8 & 16 **Title:** Connor's Preschool ADHD Questionnaire **Type:** SECONDARY ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** OG001 **Title:** Kuvan Following Active Treatment #### Outcome Measure 7 **Description:** This is a 58-item informant-based, factor-analyzed scale comprised of a total scale and 5 subscales that generate raw scores. Scores based on a likert scale ranging from 0-3 where 0 is not a problem to 3 where the problem is severe. Subscales include: Irritability, Social Withdrawal, Stereotypic Behaviors, Hyperactivity and Inappropriate Speech. Total maximum score is 174. Higher subscale scores indicate more symptoms. Scores are totaled to compute subscale scores. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. The mixed-effects models accounted for each participant's outcome data at each time point. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** all participants who completed the open label extension were analyzed. **Reporting Status:** POSTED **Time Frame:** Weeks baseline (week 16 from CHC-0901), 8 and 16. Primary outcome assessment looked at change between baseline (week 16 from CHC-0901 and week 16 of CHC-0902). **Title:** Aberrant Behavior Checklist (ABC) **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** OG001 **Title:** Kuvan Following Active Treatment #### Outcome Measure 8 **Description:** This is not a standardized measure but instead a set of questions, both closed and open ended, asked of families about their child's response to the medication. Used for determining whether treatment needed to be discontinued. **Population Description:** Data were not specifically analyzed but used instead to determine whether treatment needed to be discontinued. The data cannot now be provided as the research team has since disbanded and it is not possible to reanalyze the data at this time. **Reporting Status:** POSTED **Time Frame:** Cummulative throughout study **Title:** Adverse Events Reporting **Type:** SECONDARY ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** OG000 **Title:** Kuvan Following Placebo ##### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** OG001 **Title:** Kuvan Following Active Treatment ### Participant Flow Module #### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on placebo. **ID:** FG000 **Title:** Kuvan Following Placebo #### Group **Description:** Kuvan® (sapropterin) will be administered to all subjects at 20 mg/kg/day for 16 weeks. Participants in this arm received Kuvan following the randomized control trial in which they were on active medication. **ID:** FG001 **Title:** Kuvan Following Active Treatment #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 21 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 15 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 15 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 5 **Pre-Assignment Details:** All participants who consented went straight from the randomized control trial in 0901 (NCT00850070) to entering this trial. No washout period was needed. No participants were excluded who had completed the previous trial. **Recruitment Details:** Recruitment spanned from 08/09 - 10/11. Only individuals who completed 0901 (NCT00850070) were eligible to participate in this study thus recruitment was restricted to those already enrolled in that trial. When participants were at their 12-week visit for 0901 (NCT00850070) they were asked if they wanted to continue in the open label extension. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02356679 **Brief Title:** Efficacy and Safety of Eupasidin-s Tab.(EUPASIDIN-S) in Gastritis Patients **Official Title:** A Phase 4, Multicenter, Randomized, Open, Active Drug Comparative Trial to Evaluated the Efficacy and Safety of EUPASIDIN-S Tab. in Gastritis Patients #### Organization Study ID Info **ID:** EUPASIDIN-S_P4 #### Organization **Class:** INDUSTRY **Full Name:** Chong Kun Dang Pharmaceutical ### Status Module #### Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-08-24 **Type:** ESTIMATED **Last Update Submit Date:** 2015-08-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Start Date **Date:** 2014-08 **Status Verified Date:** 2015-08 #### Study First Post Date **Date:** 2015-02-05 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-02 **Study First Submit QC Date:** 2015-02-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Chong Kun Dang Pharmaceutical #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is evaluate the Efficacy and Safety of EUPASIDIN-S Tab. in Gastritis Patients. ### Conditions Module **Conditions:** - Acute Gastritis - Chronic Gastritis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 230 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** three times per day, 1 tab for each time, PO, during 2weeks **Intervention Names:** - Drug: Eupasidin-s Tab **Label:** Eupasidin-s tab. **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** three times per day, 1 tab for each time, PO, during 2weeks **Intervention Names:** - Drug: Stillen Tab. **Label:** Stillen tab. **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Eupasidin-s tab. **Description:** three times per day, 1 tab for each time, PO, during 2weeks **Name:** Eupasidin-s Tab **Other Names:** - Artemisia herb isopropanol soft ext. 60mg **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Stillen tab. **Description:** three times per day, 1 tab for each time, PO, during 2weeks **Name:** Stillen Tab. **Other Names:** - Artemisia asiatica 95% ethanol ext. 60mg **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** cure rate of erosion **Time Frame:** 2 weeks #### Secondary Outcomes **Measure:** improvement rate of erosion **Time Frame:** 2 weeks **Measure:** improvement rate of erythema **Time Frame:** 2 weeks **Measure:** improvement rate of hemorrhage **Time Frame:** 2 weeks **Measure:** improvement rate of edema **Time Frame:** 2 weeks **Measure:** improvement rate of self symptoms **Time Frame:** 2 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age is 19 years old and over, men or women 2. Patients diagnosed with acute or chronic gastritis by gastroscopy and need a treatment for gastritis symptoms 3. Patients with one or more erosions found by gastroscopy 4. Patients who voluntarily signed written informed consent may participate in the study Exclusion Criteria: 1. Patients with peptic ulcer and gastroesophageal reflux disease 2. Patients with Gastrointestinal malignant tumor or surgery related to stomach resection 3. Patients with thromboembolism and coagulation disorder 4. Patients with significant cardiovascular, pulmonary, heptic, renal primary disease 5. Patients with abnormal laboratory result at screening * Aspartate aminotransferase(AST), Alanine aminotransferase(ALT), Creatinine \> upper limit of normal range x 2 * White blood cell(WBC) \< 4,000/mm3 * Platelet \< 50,000/mm3 6. Patients administered with H2 receptor antagonists, proton pump inhibitors, muscarine receptor antagonists, other gastiritis treatment drug, protective factor builder, non-steroid anti-inflammatory drugs prior to study in 2 weeks 7. History of allergic reaction to the investigational product 8. Women either pregnant, breast feeding or possible to pregnant without contraceptive method 9. Use of other investigational drugs within 3 months prior to the study 10. Patients that investigators consider ineligible for this study **Minimum Age:** 19 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Busan **Country:** Korea, Republic of **Facility:** Inje University Busanpaik hospital **State:** Busangjin **Zip:** 614-735 **Location 2:** **City:** Jeonju **Country:** Korea, Republic of **Facility:** Chonbuk National University Hospital **State:** Deokjin-gu **Zip:** 561-712 **Location 3:** **City:** Guangju **Country:** Korea, Republic of **Facility:** Chonnam National University Hospital **State:** Dong-gu **Zip:** 501-757 **Location 4:** **City:** Wonju **Country:** Korea, Republic of **Facility:** Wonju Severance Christian Hospital **State:** Ilsan-ro **Zip:** 220-701 **Location 5:** **City:** Daejeon **Country:** Korea, Republic of **Facility:** Chungnam National University Hospital **State:** Jung-gu **Zip:** 301-721 **Location 6:** **City:** Iksan **Country:** Korea, Republic of **Facility:** Wonkwang University School of Medicine & Hospital **State:** Muwang-ro **Zip:** 570-711 **Location 7:** **City:** Daegu **Country:** Korea, Republic of **Facility:** Yeungnam University Medical Center **State:** Nam-gu **Zip:** 705-703 **Location 8:** **City:** Busan **Country:** Korea, Republic of **Facility:** Kosin University Gospel Hospital **State:** Seo-gu **Zip:** 602-702 **Location 9:** **City:** Busan **Country:** Korea, Republic of **Facility:** Dong-A University Hospital **State:** Seo-gu **Zip:** 602-812 **Location 10:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Hanyang University Medical Center **State:** Seongdong-gu **Zip:** 133-792 #### Overall Officials **Official 1:** **Affiliation:** Inje University Busanpaik Hospital **Name:** Sangyong Seol, Professor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000013272 - Term: Stomach Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M8872 - Name: Gastritis - Relevance: HIGH - As Found: Gastritis - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M16062 - Name: Stomach Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005756 - Term: Gastritis ### Intervention Browse Module - Ancestors - ID: D000000891 - Term: Anti-Infective Agents, Local - ID: D000000890 - Term: Anti-Infective Agents - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: HB - Name: Herbal and Botanical ### Intervention Browse Module - Browse Leaves - ID: M3777 - Name: Ethanol - Relevance: HIGH - As Found: Dependent - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M4215 - Name: Anti-Infective Agents, Local - Relevance: LOW - As Found: Unknown - ID: T232 - Name: Mugwort - Relevance: HIGH - As Found: Messenger - ID: T327 - Name: Wormwood - Relevance: HIGH - As Found: Messenger ### Intervention Browse Module - Meshes - ID: D000000431 - Term: Ethanol ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06384079 **Brief Title:** Duration of Ureteral Rest Prior to Ureteral Reconstruction Surgery **Official Title:** Study to Assess Duration of Ureteral Rest Prior to Ureteral Reconstruction Surgery #### Organization Study ID Info **ID:** STU00219828 #### Organization **Class:** OTHER **Full Name:** Northwestern University ### Status Module #### Completion Date **Date:** 2030-11 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-25 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-22 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-11 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-04-25 **Type:** ACTUAL **Study First Submit Date:** 2024-02-19 **Study First Submit QC Date:** 2024-04-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Northwestern University #### Responsible Party **Investigator Affiliation:** Northwestern University **Investigator Full Name:** Ziho Lee **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Our objective is to assess the effect of duration of ureteral rest, defined as time from conversion of ureteral stent to percutaneous nephrostomy, on stricture length prior to ureteral reconstruction surgery. ### Conditions Module **Conditions:** - Ureteral Stricture ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Antegrade and retrograde pyelogram will be completed prior to definitive ureteral repair **Intervention Names:** - Procedure: Antegrade and retrograde pyelogram **Label:** Endoscopic Evaluation ### Interventions #### Intervention 1 **Arm Group Labels:** - Endoscopic Evaluation **Description:** Participation in the study will guarantee that participants will receive this procedure. **Name:** Antegrade and retrograde pyelogram **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Ureteral stricture length measured by antegrade or retrograde pyelogram **Time Frame:** 2 weeks and 6 weeks post procedure #### Secondary Outcomes **Measure:** Ureteral Stricture Quality will be graded as either narrowed or obliterated segment. **Time Frame:** 2 weeks and 6 weeks post procedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * \>18 years of age * Undergoing ureteral reconstruction surgery for ureteral stricture with conversion of an indwelling stent to a percutaneous nephrostomy tube for ureteral rest * Willing to sign informed consent form * Able to read and understand informed consent form Exclusion Criteria: * \<18 years of age * Inability to provide informed consent * Members of vulnerable patient populations **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects over 18 years of age undergoing surgery to fix the ureter. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** emily.ji@nm.org **Name:** Emily Ji **Phone:** 312-695-8146 **Role:** CONTACT #### Locations **Location 1:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Email:** emily.ji@nm.org - **Name:** Emily Ji - **Phone:** 312-695-8146 - **Role:** CONTACT ***Contact 2:*** - **Name:** Ziho Lee, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Northwestern University **State:** Illinois **Status:** RECRUITING **Zip:** 60611 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2023-10-25 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 140931 - Type Abbrev: Prot - Upload Date: 2024-03-01T13:40 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020763 - Term: Pathological Conditions, Anatomical ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M6475 - Name: Constriction, Pathologic - Relevance: HIGH - As Found: Stricture - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003251 - Term: Constriction, Pathologic ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03858179 **Brief Title:** Effects of Photobiomodulation Therapy in Strength Training and Detraining in Humans **Official Title:** Effects of Photobiomodulation Therapy in Strength Training and Detraining in Humans #### Organization Study ID Info **ID:** 1781602 #### Organization **Class:** OTHER **Full Name:** University of Nove de Julho ### Status Module #### Completion Date **Date:** 2020-07-05 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-03-24 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-07-05 **Type:** ESTIMATED #### Start Date **Date:** 2019-03-25 **Type:** ACTUAL **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2019-02-28 **Type:** ACTUAL **Study First Submit Date:** 2019-02-26 **Study First Submit QC Date:** 2019-02-27 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Fundação de Amparo à Pesquisa do Estado de São Paulo #### Lead Sponsor **Class:** OTHER **Name:** University of Nove de Julho #### Responsible Party **Investigator Affiliation:** University of Nove de Julho **Investigator Full Name:** Ernesto Cesar Pinto Leal Junior **Investigator Title:** Full professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** In last years it has been demonstrated that photobiomodulation therapy (PBMT) has ergogenic effects, improving muscular performance and accelerating post-exercise recovery. However, many aspects related to these effects and its' clinical applicability remain unknown. Therefore, the aim of this project is to evaluate the ergogenic effects of PBMT in detraining after a strength training protocol. **Detailed Description:** It will be carried out a randomized, triple-blind, placebo-controlled trial. Forty-eight volunteers will be randomly allocated to four experimental groups: 1. PBMT before the strength training sessions and PBMT during the detraining period; 2. PBMT before the strength training sessions and placebo during the detraining period; 3. Placebo before the strength training sessions and PBMT during the detraining period; 4. Placebo before the strength training sessions and placebo during the detraining period . The individuals randomly allocated to the different groups will be subjected to 12 consecutive weeks of dynamic strength training involving leg-press and knee extension exercises in leg-press and leg-extension machines, respectively, 2 times a week.After the 12-week training period, the volunteers will receive the application of PBMT or placebo depending on the group to which they are allocated for 4 weeks (2 times a week) without training. The data will be collected by a blind assessor. It will be analyzed the muscular strength and the structural properties of quadriceps before starting the study (baseline), at 4, 8, and 12 weeks after starting the training period, and at 4 weeks after completing the training (detraining period), in both lower limbs. The findings will be tested for their normality using the Shapiro-Wilk test. Parametric data will be expressed as mean and standard deviation and non-parametric data as median and respective upper and lower limits. Parametric data will be analyzed by two-way repeated measures analysis of variance (ANOVA; time versus experimental group) with post-hoc Bonferroni correction. Non-parametric data will be analyzed using the Friedman test and, secondarily, the Wilcoxon signed-rank test. Data will be analyzed in terms of both their absolute values and their relationship to the percentage change based on the values established in the baseline tests. The significance level will be set at p\<0.05. ### Conditions Module **Conditions:** - Muscle Strength **Keywords:** - Photobiomodulation Therapy - Low-level Laser Therapy - Skeletal Muscle Strenght - Strength Training ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** A researcher will program the device (placebo or PMBT) and will be instructed not to inform the volunteers or other researchers as to the type of treatment (PMBT or placebo). Therefore, the researcher responsible for the treatment will be blinded to the type of treatment being administered to the volunteers. The sounds and signals emitted from the device as well as the information displayed on the screen will be identical, regardless of the type of treatment (placebo or PBMT). **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** PBMT applied before the strength training sessions (12 weeks, 2 times a week) and PBMT applied during the detraining period (4 weeks, 2 times a week). **Intervention Names:** - Device: PBMT **Label:** PBMT + training/ PBMT + detraining **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** PBMT applied before the strength training sessions (12 weeks, 2 times a week) and placebo applied during the detraining period (4 weeks, 2 times a week). **Intervention Names:** - Device: PBMT - Device: Placebo **Label:** PBMT + training/ placebo + detraining **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo applied before the strength training sessions (12 weeks, 2 times a week) and PBMT applied during the detraining period (4 weeks, 2 times a week). **Intervention Names:** - Device: PBMT - Device: Placebo **Label:** Placebo + training/ PBMT + detraining **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Placebo applied before the strength training sessions (12 weeks, 2 times a week) and placebo applied during the detraining period (4 weeks, 2 times a week). **Intervention Names:** - Device: Placebo **Label:** Placebo + training/ placebo + detraining **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - PBMT + training/ PBMT + detraining - PBMT + training/ placebo + detraining - Placebo + training/ PBMT + detraining **Description:** PBMT will be applied bilaterally using the direct contact method with light pressure on the skin to 6 sites of the anterior thigh (2 medial, 2 lateral, and 2 central). A 12-diode cluster, with 4 905-nm laser diodes (12.5W peak power for each diode), 4 875-nm LED diodes (17.5 mW mean power for each diode), and 4 640-nm LED diodes (15 mW mean power for each diode), manufactured by Multi Radiance Medical® (Solon, OH, USA), will be used to apply the PBMT. The dose used for applications during the training and/or detraining periods will be 30 Joules (J) per site (180 J per thigh). PBMT will be applied before each workout and during the detraining period, depending on the group to which the volunteers are allocated. **Name:** PBMT **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - PBMT + training/ placebo + detraining - Placebo + training/ PBMT + detraining - Placebo + training/ placebo + detraining **Description:** Placebo PBMT will be applied bilaterally using the direct contact method with light pressure on the skin to 6 sites of the anterior thigh (2 medial, 2 lateral, and 2 central). The placebo PBMT will per performed using the dose of 0 J per diode. The sounds and signals emitted from the device as well as the information displayed on the screen will be identical, regardless of the type of treatment (active or placebo). Placebo PBMT will be applied before each workout and during the detraining period, depending on the group to which the volunteers are allocated. **Name:** Placebo **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The peak torque will be measured by Maximum Voluntary Contraction (MVC) test. **Measure:** Peak Torque **Time Frame:** 16 weeks - 4 weeks after completing the training (detraining period). #### Secondary Outcomes **Description:** The peak torque will be measured by Maximum Voluntary Contraction (MVC) test. **Measure:** Peak Torque **Time Frame:** 4, 8, and 12 weeks after starting the training period. **Description:** Muscle strength will be measured by one-repetition maximum (1-RM) test. **Measure:** Muscle strength **Time Frame:** 4, 8, and 12 weeks after starting the training period, and at 4 weeks after completing the training (detraining period). **Description:** Muscle thickness will be measured by ultrasound imaging. **Measure:** Muscle thickness **Time Frame:** 4, 8, and 12 weeks after starting the training period, and at 4 weeks after completing the training (detraining period). **Description:** Muscle fascicle length will be measured by ultrasound imaging. **Measure:** Muscle fascicle length **Time Frame:** 4, 8, and 12 weeks after starting the training period, and at 4 weeks after completing the training (detraining period). **Description:** Muscle fiber pennation angle will be measured by ultrasound imaging. **Measure:** Muscle fiber pennation angle **Time Frame:** 4, 8, and 12 weeks after starting the training period, and at 4 weeks after completing the training (detraining period). ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy men; * Aged from 18 to 35 years; * Complete at least 80% of the study procedures will be included in the study. Exclusion Criteria: * History of musculoskeletal injury in the hip and knee regions in the 2 months before the study; * Become injured during the study; * Regularly use pharmacological agents and/ or nutritional supplements; * Signs and symptoms of any neurological, metabolic, inflammatory, pulmonary, oncological, or cardiovascular disease that may limit the execution of high-intensity exercises. **Gender Based:** True **Healthy Volunteers:** True **Maximum Age:** 35 Years **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** ernesto.leal.junior@gmail.com **Name:** Ernesto Cesar Pinto Leal Junior, PhD **Phone:** +55 11 33859134 **Role:** CONTACT #### Locations **Location 1:** **City:** São Paulo **Contacts:** ***Contact 1:*** - **Name:** Ernesto Cesar Pinto Leal Junior, PhD - **Phone:** +55 11 33859134 - **Role:** CONTACT **Country:** Brazil **Facility:** Laboratory of Phototherapy and Innovative Technologies in Health **Status:** RECRUITING **Zip:** 01504-001 #### Overall Officials **Official 1:** **Affiliation:** University of Nove de Julho **Name:** Ernesto Cesar Pinto Leal Junior, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Data will be shared upon request addressed to the principal investigator. **Info Types:** - STUDY_PROTOCOL - SAP - CSR **IPD Sharing:** YES ### References Module #### References **Citation:** de Paiva PRV, Casalechi HL, Tomazoni SS, Machado CDSM, Vanin AA, Baroni BM, de Carvalho PTC, Leal-Junior ECP. Effects of photobiomodulation therapy combined to static magnetic field in strength training and detraining in humans: protocol for a randomised placebo-controlled trial. BMJ Open. 2019 Oct 28;9(10):e030194. doi: 10.1136/bmjopen-2019-030194. **PMID:** 31662370 ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01668979 **Brief Title:** Assessment of a New System to Detect, Quantify and Treat Near Falls in Older Adults **Official Title:** Assessment of a New System to Detect, Quantify and Treat Near Falls in Older Adults #### Organization Study ID Info **ID:** TASMC-12-NG-0363-CTIL #### Organization **Class:** OTHER_GOV **Full Name:** Tel-Aviv Sourasky Medical Center ### Status Module #### Completion Date **Date:** 2013-09 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2012-08-20 **Type:** ESTIMATED **Last Update Submit Date:** 2012-08-16 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2013-09 **Type:** ESTIMATED #### Start Date **Date:** 2012-09 **Status Verified Date:** 2012-08 #### Study First Post Date **Date:** 2012-08-20 **Type:** ESTIMATED **Study First Submit Date:** 2012-08-16 **Study First Submit QC Date:** 2012-08-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Tel-Aviv Sourasky Medical Center #### Responsible Party **Investigator Affiliation:** Tel-Aviv Sourasky Medical Center **Investigator Full Name:** Michal Roll PhD,MBA **Investigator Title:** Director of Research and Development **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study is aimed to assess a new system for the automatic detection, quantification and treatment of Near Fall (NF) episodes in healthy older adults with a history of falls. The system is comprized of a treadmill and a virtual reality simulation which provides a motor-cognitive challenge to provoke NF. The challenges provided by the system are individualized and using machine learning algorithms will enable the identification and detection of NF under different conditions and allow for the most suitable treatment. ### Conditions Module **Conditions:** - Idiopathic Fallers ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** the new system comprises of a treadmill and a virtual reality simulation that will be used to induce Near Falls in healthy older adults with a history of falls. **Intervention Names:** - Device: new system to detect Near Falls **Label:** new system to detect Near Falls ### Interventions #### Intervention 1 **Arm Group Labels:** - new system to detect Near Falls **Description:** We will invite healthy older adults with a history of falls to try the new system and assess whether the new system can induce, detect and quantify Near Fall episodes **Name:** new system to detect Near Falls **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** usability of the system to detect Near Falls **Time Frame:** one year #### Secondary Outcomes **Measure:** Near Fall severity **Time Frame:** one year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy older adults with a history of falls or complaints of gait instability 2. Able to walk independently for at least 10 minutes Exclusion Criteria: 1. Systemic chronic or acute pathologies: 1. Ischemic heart disease 2. Orthopedic or Rheumatic diseases 3. Severe vision problems 4. Neurological disease: PD, AD, CVA 2. Patients who underwent brain surgery in the last 6 months prior to the study **Healthy Volunteers:** True **Maximum Age:** 85 Years **Minimum Age:** 60 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Healthy older adults with a history of falls ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** nirg@tasmc.health.gov.il **Name:** Nir Giladi, MD **Phone:** +972 3 6974958 **Role:** CONTACT **Contact 2:** **Email:** anatmi@tasmc.health.gov.il **Name:** Anat Mirelman, PhD **Phone:** +972 3 6973960 **Role:** CONTACT #### Locations **Location 1:** **City:** Tel Aviv **Contacts:** ***Contact 1:*** - **Email:** nirg@tasmc.health.gov.il - **Name:** Nir Giladi, MD - **Phone:** +972 3 6974958 - **Role:** CONTACT ***Contact 2:*** - **Name:** Anat Mirelman, PhD - **Role:** SUB_INVESTIGATOR **Country:** Israel **Facility:** Tel Aviv Sourasky Medical Center **Zip:** 64239 #### Overall Officials **Official 1:** **Affiliation:** Tel-Aviv Sourasky Medical Center **Name:** Nir Giladi, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05047679 **Acronym:** B²EARS **Brief Title:** The Effectiveness of Pain Neuroscience Education in At-risk Patients Following Surgery for Lumbar Radiculopathy **Official Title:** The Effectiveness of Pain Neuroscience Education in Patients at Risk for Unfavorable Outcome Following Surgery for Lumbar Radiculopathy: A Multicentric Randomized Controlled Trial #### Organization Study ID Info **ID:** FWOSB108 #### Organization **Class:** OTHER **Full Name:** Vrije Universiteit Brussel #### Secondary ID Infos **Domain:** Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO) **ID:** 1S61521N **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2023-10-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-22 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2023-10-16 **Type:** ACTUAL #### Start Date **Date:** 2021-09-30 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2021-09-17 **Type:** ACTUAL **Study First Submit Date:** 2021-09-03 **Study First Submit QC Date:** 2021-09-13 **Why Stopped:** Recruitment issues that could not be resolved in a timely manner. ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Universitair Ziekenhuis Brussel **Class:** OTHER **Name:** Research Foundation Flanders #### Lead Sponsor **Class:** OTHER **Name:** Vrije Universiteit Brussel #### Responsible Party **Investigator Affiliation:** Vrije Universiteit Brussel **Investigator Full Name:** Jo Nijs **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study aims to assess the effectiveness of perioperative pain neuroscience education (PPNE) in patients who are at risk for unfavorable outcome following surgery for lumbar radiculopathy. Although most of these surgeries are successful, 23-28% of patients report chronic pain and disability following surgery. Many preoperative factors are associated with an unfavorable surgical outcome, including maladaptive cognitive and emotional factors. Yet, current preoperative education, which focuses on anatomy and biomechanics of the lumbar spine, is ineffective in changing those maladaptive factors. PPNE was introduced as an innovative therapy that addresses modifiable risk factors in patients undergoing surgery for lumbar radiculopathy. PPNE reconceptualizes pain, informs patients about their pain development and is well established for improving maladaptive cognitions in several chronic pain-populations. Hence, we hypothesize that PPNE will be more effective than perioperative biomedical education in improving postsurgical quality of life, pain, analgesic use and return to work in patients at risk for unfavorable outcome following surgery for lumbar radiculopathy. First, a multicentric randomized controlled trial will compare the therapy effects of PPNE to perioperative biomedical education in these at-risk patients. Next, the mediating role of changes in maladaptive cognitions, such as fear of movement and pain catastrophizing, on the therapy effect of PPNE will be investigated. **Detailed Description:** Study rationale: Lumbar radiculopathy is described as uni- or bilateral leg pain which is often worse than back pain, with pain radiating in the related dermatomes and possible associations with sensory and/or motor symptoms or even deficits. Although surgical intervention for lumbar radiculopathy is often considered anatomically successful, several patients undergoing similar surgeries continue to experience pain and disability. Furthermore, patients developing such an unfavorable outcome also report decreased quality of life values, as well as an increase in analgesic use and health care utilization. Such unfavorable outcome is associated with a multitude of preoperative factors, including but not limited to maladaptive cognitive and emotional factors (e.g., fear of movement, pain catastrophizing, anxiety, distress and depression), preexisting chronic pain and long duration of preoperative sick leave. In line with this, it has been suggested that maladaptive psychological factors require special attention and optimization before surgery. Perioperative pain neuroscience education (PPNE) is such an intervention addressing these maladaptive psychological factors, such as fear of movement and pain catastrophizing. Therefore, a study assessing the effectiveness of PPNE on surgical outcome in at-risk patients undergoing surgery for lumbar radiculopathy is warranted. Rationale for study design: The present study builds on the evidence provided by the study of Louw et al. (2014 \& 2016) which was a randomized controlled trial comparing PPNE with no supplemental intervention in patients undergoing surgery for lumbar radiculopathy. As such, we will conduct a multicentric randomized controlled trial investigating the therapy effect of PPNE specifically in patients with lumbar radiculopathy at risk for unfavorable surgical outcome. Doing this we will address several knowledge gaps by comparing two balanced therapy groups (PPNE vs perioperative biomedical education (PBE)), therefore overcoming potential bias due to unbalanced treatment arms, by adding several relevant outcome measures, and by targeting high-risk patients rather than all patients undergoing surgery. Study objectives: The primary objective is to examine whether PPNE is more effective than PBE in improving postoperative quality of life at 6 weeks follow-up in patients undergoing surgery for lumbar radiculopathy at risk for unfavorable surgical outcome. Secondary objectives include: 1) to explore baseline associations between pain cognitions, quality of life and pain in patients scheduled for surgery for lumbar radiculopathy at risk for unfavorable outcome; 2) to examine whether PPNE is more effective than PBE in obtaining good surgical results concerning quality of life, pain, analgesic use, return to work, self-reported symptoms of central sensitization and pain cognitions at 6 weeks, 6 months and 1 year post-surgery and 3) to reveal the mediating role of changes in pain cognitions in the mechanism behind the therapy effect of PPNE in patients undergoing surgery for lumbar radiculopathy at risk for unfavorable outcome. Study design: This study is a randomized controlled trial with one-year follow-up using preoperative patient screening based on chronic pain (≥ 6 months), kinesiophobia (Tamp Scale for Kinesiophobia ≥ 37/68) and pain catastrophizing (Pain Catastrophizing Scale ≥ 30/52). Eligible patients undergoing surgery for lumbar radiculopathy will be randomized and receive either the experimental intervention, i.e., PPNE, or the control intervention, i.e., PBE. Follow-up assessments will be organized at 6 weeks, 6 months and 12 months following the surgery. Patient recruitment: All patients scheduled for surgery for lumbar radiculopathy in one of the participating hospitals will be contacted by telephone by the coordinating investigator. First, patients will be informed about the project and asked if they are willing to participate. When patients agree with participating in the study, they will be screened for potential eligibility using the in- and exclusion criteria. Following the initial screening, patients will have to meet an additional set of presurgical criteria (i.e., chronic pain, pain catastrophizing and kinesiophobia) to assess whether they are at risk for unfavorable surgical outcome, and therefore eligible for inclusion in the study sample. To screen for these presurgical criteria, patients eligible for further screening after the initial telephone interview, will be asked to complete an online survey questioning the three aforementioned criteria. The first page of the online survey will inform the patients once again about the goal of the screening and all patients will have to indicate their consent (by checking a box) before they can proceed to the actual questionnaire. Randomization and blinding procedures: Following baseline assessments, participants will be randomized to one of both treatment groups. Concealed randomization will be prepared using a stratified permuted block allocation with stratification for treatment center. Randomization will be executed by an independent researcher who is not involved in the recruitment, assessments, treatment provision or statistical analyses. Patients will not know whether the intervention they receive is the experimental or the control intervention, however they will of course be aware of the content of the received intervention. A co-investigator, who will be responsible for baseline assessment and all follow-up assessments, will also be blinded to group allocation. With regard to this, patients will be asked not to communicate with the co-investigator about the intervention they received. The therapists providing the experimental treatment will not be involved in providing the control intervention and vice versa. Sample size: Sample size was calculated to be 108 (54 per intervention group) based on a medium effect size of 0.6, α of 0.05, desired power of 0.80, an allocation ratio (N2/N1) of 1 and an anticipated loss to follow-up of 20%. A longitudinal pilot study in patients undergoing surgery for lumbar radiculopathy and who were retrospectively selected based on chronic pain (≥3 months), kinesiophobia (Tampa Scale for Kinesiophobia ≥37/68) and pain catastrophizing (Pain Catastrophizing Scale ≥30/52) was performed and evaluated the effect of PPNE on Short-Form 36-item, these results were used to determine the effect size for the sample size calculation. Statistical analysis: Descriptive and correlation analyses will be performed on the baseline data. An AN(C)OVA repeated measures analysis will be used to evaluate treatment effects (primary and secondary objective). Lastly, a mediation analysis will be performed to examine the potential mediating role of changes in pain cognitions on the therapy effect of PPNE on quality of life. ### Conditions Module **Conditions:** - Lumbar Radiculopathy **Keywords:** - Biomedical Education - Pain Neuroscience Education - Lumbar surgery - Education - Chronic pain - Kinesiophobia - Catastrophization - Perioperative Education ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Masking Description:** Only the participant and the person responsible for the monitoring of the baseline and follow-up assessments will be masked. **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 6 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in the experimental treatment group will receive Perioperative Pain Neuroscience Education, including a preoperative session 3 days before the surgery, access to an educational web application and a postoperative session 2 days following the surgery. Both education sessions will be face-to-face and will last approximately 60 minutes. **Intervention Names:** - Behavioral: Perioperative Pain Neuroscience Education **Label:** Perioperative Pain Neuroscience Education **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients in the control treatment group will receive Perioperative Biomedical Education, including a preoperative session 3 days before the surgery, access to an educational web application and a postoperative session 2 days following the surgery. Both education sessions will be face-to-face and will last approximately 60 minutes. **Intervention Names:** - Behavioral: Perioperative Biomedical Education **Label:** Perioperative Biomedical Education **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Perioperative Pain Neuroscience Education **Description:** Perioperative pain neuroscience education addresses modifiable preoperative risk factors, and in particular cognitive and emotional risk factors, such as fear of movement and pain catastrophizing (i.e., excessively negative orientation toward pain). This education is a cognitive-based therapeutic intervention which reconceptualizes pain, informs patients about what to expect from the evolution of their pain, de-emphasizes the patho-anatomical content and focuses on factors contributing to the development of pain. It explains this all within a biopsychosocial framework, which means that it aims to optimize patients' beliefs. Furthermore, it intends to reassure the patient about the decision to have surgery, to potentially decrease perioperative distress. **Name:** Perioperative Pain Neuroscience Education **Other Names:** - Pain Education **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Perioperative Biomedical Education **Description:** Perioperative biomedical education will discuss the anatomy, physiology and biomechanics of the lumbar spine with the patient. Additionally, the content of this education includes the expected course of postoperative back and leg pain, as well as ergonomic advice on patient-specific daily activities. This education will be given within a biomedical framework, which means that it aims to explain the patients' complaints and recovery while focusing on anatomy and biomechanics, as opposed to patients' beliefs and cognitions. **Name:** Perioperative Biomedical Education **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Patients will be asked to fulfil a demographic questionnaire concerning their age, gender, height, weight, education level, household composition and professional situation. **Measure:** Demographic data **Time Frame:** Baseline (1 week before surgery) **Description:** Health literacy will be evaluated using the 16-item questionnaire from the Health Literacy Study Europe (HLS-EU-Q16). The HLS-EU-Q16 is the short form of the HLS-EU-Q47, as developed during the European Health Literacy Survey (HLS-EU). The total score is calculated as the sum of all dichotomized answers ('fairly' or 'very' easy = 1; 'fairly' or 'very' difficult = 0) and ranges between 0 and 16. Correlations between the results of the HLS-EU-Q16 and the HLS-EU-Q47 were found to be high and the clinimetric properties of the short form are considered to be acceptable. **Measure:** Health literacy **Time Frame:** Baseline (1 week before surgery) #### Primary Outcomes **Description:** Change in health-related quality of life will be be assessed by the Short Form 36-item Health Survey (SF-36). The SF-36 contains 8 subscales: physical, emotional, social and role functioning, bodily pain, mental health, vitality and general health. The psychometric properties are well established in a wide variety of patient populations, and its responsiveness to change following surgical interventions is superior than other generic health status measurement scales commonly used in evaluations of interventions for chronic, disabling pain. Additionally, the 5-level EuroQol 5-dimensions (EQ-5D\*), which also has good measurement properties, will be used to calculate the change in health utility values between baseline and 1 year post-surgery. **Measure:** Change in health-related quality of life **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery* #### Secondary Outcomes **Description:** Pain intensity for the leg and low back will be assessed by a series of 100mm Visual Analogue Scales (VAS). The VAS pain score is believed to be reliable, valid and sensitive to change. More specifically the patient will be asked to rate their highest and lowest pain severity in the last 24 hours for back or leg pain, and mean pain in the last 24 hours, as well as current pain for the back and leg separately. **Measure:** Change in self-reported leg and low back pain intensity **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery **Description:** Analgesic use will be assessed by a self-reported recall questionnaire, which has been proven to be valid and feasible for a period up to 6 months. Patients will be asked to report the name of the medication, frequency of use, dose and whether it was prescribed or not. Also, patients are asked to indicate whether the medication was taken because of their back or leg pain, and if not, what the reason was for taking this medication. **Measure:** Change in analgesic use **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery **Description:** Return to work will be assessed by asking patients whether they already resumed professional activities, and if yes, since when they resumed work and to what extent. Also, patients will be given the opportunity to mention whether they had to change jobs or job content for effective work resumption. Additionally, prescribed sick leave is recorded separately by asking patients to report the dates of the doctor's notes. **Measure:** Return to work (6 weeks post-surgery) **Time Frame:** 6 weeks post-surgery **Description:** Return to work will be assessed by asking patients whether they resumed or maintained professional activities, and if yes, since when they resumed work and to what extent they are currently working. Also, patients will be given the opportunity to mention whether they had to change jobs or job content for effective work resumption or maintenance. Additionally, prescribed sick leave is recorded separately by asking patients to report the dates of the doctor's notes. **Measure:** Return to work (6 months post-surgery) **Time Frame:** 6 months post-surgery **Description:** Return to work will be assessed by asking patients whether they resumed or maintained professional activities, and if yes, since when they resumed work and to what extent they are currently working. Also, patients will be given the opportunity to mention whether they had to change jobs or job content for effective work resumption or maintenance. Additionally, prescribed sick leave is recorded separately by asking patients to report the dates of the doctor's notes. **Measure:** Return to work (1 year post-surgery) **Time Frame:** 1 year post-surgery **Description:** The Dutch Central Sensitization Inventory (CSI) will be used to assess self-reported symptoms of central sensitization. The CSI consists of 25 statements about symptoms that people with chronic pain might encounter, such as sensitivity to light or concentration difficulties. A reported higher degree of self-symptomology regarding central sensitization indicates the potential presence of hypersensitivity. It shows good validity for assessing symptoms of central sensitization in patients with chronic pain. **Measure:** Change in self-reported symptoms of central sensitization **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery **Description:** Kinesiophobia will be assessed with the Tampa Scale for Kinesiophobia (TSK), which is a questionnaire consisting of 17 items, and the total score can range from 17 to 68 with higher scores indicating higher levels of kinesiophobia. It has good clinimetric properties in patients with low back pain. **Measure:** Change in kinesiophobia **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery **Description:** Pain catastrophizing will be assessed with the Pain Catastrophizing Scale (PCS), which has well-established clinimetric properties. It consists of 13 items describing different thought and feelings that individuals may experience when they are experiencing pain, total scores range from 0 to 52, with higher scores indicating more catastrophizing. **Measure:** Change in pain catastrophizing **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery **Description:** Pain hypervigilance will be assessed using the Pain Vigilance and Awareness Questionnaire (PVAQ), which is designed to measure attention to pain by assessing awareness, consciousness, vigilance and observation of pain. This questionnaire consists of 16 items and total scores can range from 0 to 90, with higher scores indicating more pain vigilance. These items have demonstrated good internal consistency reliability (Cronbach's alpha = 0.86) in patients with chronic low back pain. **Measure:** Change in pain hypervigilance **Time Frame:** Change between baseline (1 week before surgery) and 6 weeks post-surgery, baseline and 6 months post-surgery, baseline and 1 year post-surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Scheduled for surgery for lumbar radiculopathy * Aged 18 years or older * Willing to comply with pre-determined follow-up * Speaking and reading Dutch fluently * No new treatments/medication 3 weeks prior to participation and during the trial * Having chronic back and/or leg pain ≥ 6 months * Scoring ≥ 37/68 on the Tampa Scale for Kinesiophobia * Scoring ≥ 30/52 on the Pain Catastrophizing Scale Exclusion Criteria: * Surgery for another condition * Symptoms of cord compression or bilateral leg pain * Other chronic illness characterized by chronic pain * Other chronic rheumatoid, neurological, endocrinological, psychiatric or cognitive disorders * Indicated cognitive impairment (Scoring ≤11/15 on the 5-min Telephone Montreal Cognitive Assessment) * Pregnant or have given birth during the past year * No access to computer, or mobile device at home * Complications during the surgery **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bornem **Country:** Belgium **Facility:** AZ Rivierenland **State:** Antwerpen **Zip:** 2880 **Location 2:** **City:** Geel **Country:** Belgium **Facility:** AZ Sint-Dimpna **State:** Antwerpen **Zip:** 2440 **Location 3:** **City:** Jette **Country:** Belgium **Facility:** Universitair Ziekenhuis Brussel **State:** Brussel **Zip:** 1090 **Location 4:** **City:** Antwerpen **Country:** Belgium **Facility:** ZNA Middelheim **Zip:** 2020 #### Overall Officials **Official 1:** **Affiliation:** Vrije Universiteit Brussel **Name:** Jo Nijs, Prof. Dr. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Only researchers who intend to use and analyze the pseudonymized data for the purpose of scientific research can request access to the data. Additionally, researchers who intend to use the data are required to provide a statistical plan including the predetermined research question and detailing the intended analyses. Also, details regarding the storage of the shared data should be provided to ensure that the researchers took the appropriate measures to establish a secure storage location for the shared data. A request for data access can be send to the central contact person and a data sharing agreement will be signed by both parties. **Description:** Given the confidential nature of the collected data, the raw data will not be made open access following the study. However, excluding all possible personal identifiable data (e.g., date of birth and date of surgery), the pseudonymized data of all outcome measures (i.e., health-related quality of life, pain intensity, analgesic use, return to work, self-reported symptoms of central sensitization, pain catastrophizing, kinesiophobia and pain hypervigilance), as well as general demographic data (e.g., age, height, weight and education level) will be made available via a data repository with restricted access. **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** Following the study, the data will be stored at a data repository with restricted access for 10 years. ### References Module #### References **Citation:** Ickmans K, Moens M, Putman K, Buyl R, Goudman L, Huysmans E, Diener I, Logghe T, Louw A, Nijs J. Back school or brain school for patients undergoing surgery for lumbar radiculopathy? Protocol for a randomised, controlled trial. J Physiother. 2016 Jul;62(3):165. doi: 10.1016/j.jphys.2016.05.009. Epub 2016 Jun 11. **PMID:** 27298051 **Citation:** Louw A, Butler DS, Diener I, Puentedura EJ. Development of a preoperative neuroscience educational program for patients with lumbar radiculopathy. Am J Phys Med Rehabil. 2013 May;92(5):446-52. doi: 10.1097/PHM.0b013e3182876aa4. **PMID:** 23478459 **Citation:** Louw A, Diener I, Landers MR, Puentedura EJ. Preoperative pain neuroscience education for lumbar radiculopathy: a multicenter randomized controlled trial with 1-year follow-up. Spine (Phila Pa 1976). 2014 Aug 15;39(18):1449-57. doi: 10.1097/BRS.0000000000000444. **PMID:** 24875964 **Citation:** Wilson CA, Roffey DM, Chow D, Alkherayf F, Wai EK. A systematic review of preoperative predictors for postoperative clinical outcomes following lumbar discectomy. Spine J. 2016 Nov;16(11):1413-1422. doi: 10.1016/j.spinee.2016.08.003. Epub 2016 Aug 4. **PMID:** 27497886 **Citation:** den Boer JJ, Oostendorp RA, Beems T, Munneke M, Oerlemans M, Evers AW. A systematic review of bio-psychosocial risk factors for an unfavourable outcome after lumbar disc surgery. Eur Spine J. 2006 May;15(5):527-36. doi: 10.1007/s00586-005-0910-x. Epub 2005 May 25. **PMID:** 15915334 **Citation:** den Boer JJ, Oostendorp RA, Beems T, Munneke M, Evers AW. Continued disability and pain after lumbar disc surgery: the role of cognitive-behavioral factors. Pain. 2006 Jul;123(1-2):45-52. doi: 10.1016/j.pain.2006.02.008. Epub 2006 Mar 24. **PMID:** 16563624 **Citation:** Taylor RS, Taylor RJ. The economic impact of failed back surgery syndrome. Br J Pain. 2012 Nov;6(4):174-81. doi: 10.1177/2049463712470887. **PMID:** 26516490 **Citation:** Inoue S, Kamiya M, Nishihara M, Arai YP, Ikemoto T, Ushida T. Prevalence, characteristics, and burden of failed back surgery syndrome: the influence of various residual symptoms on patient satisfaction and quality of life as assessed by a nationwide Internet survey in Japan. J Pain Res. 2017 Apr 6;10:811-823. doi: 10.2147/JPR.S129295. eCollection 2017. **PMID:** 28435318 **Citation:** Manca A, Eldabe S, Buchser E, Kumar K, Taylor RS. Relationship between health-related quality of life, pain, and functional disability in neuropathic pain patients with failed back surgery syndrome. Value Health. 2010 Jan-Feb;13(1):95-102. doi: 10.1111/j.1524-4733.2009.00588.x. Epub 2009 Aug 20. **PMID:** 19695004 **Citation:** Van Oosterwijck J, Nijs J, Meeus M, Truijen S, Craps J, Van den Keybus N, Paul L. Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study. J Rehabil Res Dev. 2011;48(1):43-58. doi: 10.1682/jrrd.2009.12.0206. **PMID:** 21328162 **Citation:** Meeus M, Nijs J, Van Oosterwijck J, Van Alsenoy V, Truijen S. Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial. Arch Phys Med Rehabil. 2010 Aug;91(8):1153-9. doi: 10.1016/j.apmr.2010.04.020. **PMID:** 20684894 **Citation:** Louw A, Diener I, Landers MR, Zimney K, Puentedura EJ. Three-year follow-up of a randomized controlled trial comparing preoperative neuroscience education for patients undergoing surgery for lumbar radiculopathy. J Spine Surg. 2016 Dec;2(4):289-298. doi: 10.21037/jss.2016.12.04. **PMID:** 28097246 **Citation:** Butler D, Moseley GL. Explain pain: Adelaide: NOI Group Publishing; 2003 **Citation:** van Wilgen CP, Nijs J. Pijneducatie: een praktische handleiding voor (para)medici: Bohn Stafleu van Loghum; 2010. **Citation:** Louw A. Your Nerves Are Having Back Surgery. International Spine and Pain Institute, Minneapolis, U.S.A.; 2012. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010523 - Term: Peripheral Nervous System Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M29442 - Name: Chronic Pain - Relevance: LOW - As Found: Unknown - ID: M2922 - Name: Kinesiophobia - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M14689 - Name: Radiculopathy - Relevance: HIGH - As Found: Radiculopathy - ID: M13432 - Name: Peripheral Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011843 - Term: Radiculopathy ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03732079 **Brief Title:** Inferior Vena Cava Diameter and Postpartum Hemorrhage **Official Title:** The Correlation Between Inferior Vena Caval Diameter and the Volume of Postpartum Blood Loss #### Organization Study ID Info **ID:** HaEmek #### Organization **Class:** OTHER **Full Name:** HaEmek Medical Center, Israel ### Status Module #### Completion Date **Date:** 2019-04-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2018-11-06 **Type:** ACTUAL **Last Update Submit Date:** 2018-11-05 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2018-11-10 **Type:** ESTIMATED **Status Verified Date:** 2018-11 #### Study First Post Date **Date:** 2018-11-06 **Type:** ACTUAL **Study First Submit Date:** 2018-11-04 **Study First Submit QC Date:** 2018-11-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** HaEmek Medical Center, Israel #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Excessive bleeding after normal birth or cesarean section is defined as blood loss of 1000 mL or more (clinically estimated) within 24 hours after birth. It occurs in about 5% among postpartum women. Postpartum hemorrhage is a leading cause of morbidity and mortality among women giving birth. Postpartum hemorrhage may lead to hemorrhagic shock, renal failure, respiratory failure, need for surgical intervention, blood transfusion and hysterectomy. The cornerstone of effective treatment is rapid diagnosis and intervention in time. However, in a number of cases there is an underestimation of the volume of blood loss which may lead to delay in diagnosis and treatment. The consequences are even graver in women who delivered by a cesarean section, since unlike a normal birth in which the bleeding is external and visible, the bleeding is usually intra-abdominal, and so the delay in diagnosis may be even longer. The Inferior Vena Cava (IVC) is a flexible blood vessel sensitive to intravascular blood volume, and its diameter varies accordingly. Its diameter reflects the pressure in the right atrium, which is a measure of the cardiac preload. A number of studies have shown that the IVC diameter changes, before the variations in vital and clinical signs. Recently, IVC diameter has been assessed as an assessment of intravenous fluid balance in hemodynamically stable patients with a risk of sub-volume shock. The authors concluded that the IVC measurement is a good noninvasive method, compared to catheter insertion into the right atrium, and it is available as a bedside procedure. In obstetrics the use of IVC to determine blood loos was not widely examined and there is no information regarding the use of IVC diameter as a predictor or as a detection method of postpartum bleeding. In this study the investigators aim to examine the correlation between IVC diameter and the volume of postpartum blood loss. ### Conditions Module **Conditions:** - Other Immediate Postpartum Hemorrhage, With Delivery **Keywords:** - Inferior Vena Cava Diameter ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 108 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Women with early postpartum hemorrhage. **Intervention Names:** - Diagnostic Test: Ultrasound **Label:** Research group #### Arm Group 2 **Description:** Postpartum women without abnormal bleeding. **Intervention Names:** - Diagnostic Test: Ultrasound **Label:** Control group ### Interventions #### Intervention 1 **Arm Group Labels:** - Control group - Research group **Description:** Ultrasound to measure the IVC diameter. The IVC diameter will be measured in the inspirium and the expirium, and the collapsibility index will be recorded. **Name:** Ultrasound **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Measure:** To examine the correlation between IVC diameter and the volume of postpartum blood loss. **Time Frame:** 6 months #### Secondary Outcomes **Measure:** To create a normogram of IVC diameter in postpartum women and to check whether there is a cutt-of value that appears before the onset of clinical signs of blood loss. **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women over the age of 18 after birth * Single pregnancy * Vaginal birth * Term pregnancy (gestational age between week 37-42) * The newborn is appropriate for gestational age (10-90 percentile) Exclusion Criteria: * Gestational or pre-pregnancy hypertension * Heart, liver, or chronic kidney disease * Women who delivered newborn with major malformation **Gender Based:** True **Gender Description:** postpartum women **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Postpartum women. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** manal.massalha@clalit.org.il **Name:** Manal Massalha, MD **Phone:** 0506415166 **Role:** CONTACT **Contact 2:** **Email:** salim_ra@clalit.org.il **Name:** Raed Salim, MD **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Emek Medical Center **Name:** Manal Massalha, Massalha **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol. 2017 Oct;130(4):e168-e186. doi: 10.1097/AOG.0000000000002351. **PMID:** 28937571 **Citation:** Callaghan WM, Kuklina EV, Berg CJ. Trends in postpartum hemorrhage: United States, 1994-2006. Am J Obstet Gynecol. 2010 Apr;202(4):353.e1-6. doi: 10.1016/j.ajog.2010.01.011. **PMID:** 20350642 **Citation:** Byeon K, Choi JO, Yang JH, Sung J, Park SW, Oh JK, Hong KP. The response of the vena cava to abdominal breathing. J Altern Complement Med. 2012 Feb;18(2):153-7. doi: 10.1089/acm.2010.0656. **PMID:** 22339104 **Citation:** Grant E, Rendano F, Sevinc E, Gammelgaard J, Holm HH, Gronvall S. Normal inferior vena cava: caliber changes observed by dynamic ultrasound. AJR Am J Roentgenol. 1980 Aug;135(2):335-8. doi: 10.2214/ajr.135.2.335. **PMID:** 6773338 **Citation:** Kusaba T, Yamaguchi K, Oda H, Harada T. Echography of inferior vena cava for estimating fluid removed from patients undergoing hemodialysis. Nihon Jinzo Gakkai Shi. 1994 Aug;36(8):914-20. **PMID:** 7933667 **Citation:** Lyon M, Blaivas M, Brannam L. Sonographic measurement of the inferior vena cava as a marker of blood loss. Am J Emerg Med. 2005 Jan;23(1):45-50. doi: 10.1016/j.ajem.2004.01.004. **PMID:** 15672337 **Citation:** Rahman NH, Ahmad R, Kareem MM, Mohammed MI. Ultrasonographic assessment of inferior vena cava/abdominal aorta diameter index: a new approach of assessing hypovolemic shock class 1. Int J Emerg Med. 2016 Dec;9(1):8. doi: 10.1186/s12245-016-0101-z. Epub 2016 Feb 19. **PMID:** 26894896 **Citation:** Hernandez CA, Reed KL, Juneman EB, Cohen WR. Changes in Sonographically Measured Inferior Vena Caval Diameter in Response to Fluid Loading in Term Pregnancy. J Ultrasound Med. 2016 Feb;35(2):389-94. doi: 10.7863/ultra.15.04036. Epub 2016 Jan 18. **PMID:** 26782160 **Citation:** Ryo E, Unno N, Hagino D, Kozuma S, Nagasaka T, Taketani Y. Inferior vena cava diameter and the risk of pregnancy-induced hypertension and fetal compromise. Int J Gynaecol Obstet. 1999 May;65(2):143-8. doi: 10.1016/s0020-7292(99)00027-2. **PMID:** 10405058 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000011644 - Term: Puerperal Disorders - ID: D000014592 - Term: Uterine Hemorrhage ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M9559 - Name: Postpartum Hemorrhage - Relevance: HIGH - As Found: Postpartum Hemorrhage - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M14499 - Name: Puerperal Disorders - Relevance: LOW - As Found: Unknown - ID: M17340 - Name: Uterine Hemorrhage - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006473 - Term: Postpartum Hemorrhage - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Browse Branches - Abbrev: HB - Name: Herbal and Botanical - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T204 - Name: Kava - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01420679 **Brief Title:** Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients **Official Title:** A Multi-center, Randomized, Phase 3 Study of Sequential Pralatrexate Versus Observation in Patients Previously Undiagnosed Peripheral T-cell Lymphoma Who Achieved an Objective Response After Initial Treatment With CHOP-based Chemotherapy #### Organization Study ID Info **ID:** PDX-017 #### Organization **Class:** INDUSTRY **Full Name:** Spectrum Pharmaceuticals, Inc #### Secondary ID Infos **ID:** 2010-022230-81 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2017-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-11-19 **Type:** ACTUAL **Last Update Submit Date:** 2021-11-18 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2017-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-11-19 **Type:** ACTUAL **Results First Submit Date:** 2021-10-01 **Results First Submit QC Date:** 2021-11-18 #### Start Date **Date:** 2011-08 **Type:** ACTUAL **Status Verified Date:** 2021-11 #### Study First Post Date **Date:** 2011-08-22 **Type:** ESTIMATED **Study First Submit Date:** 2011-08-18 **Study First Submit QC Date:** 2011-08-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Spectrum Pharmaceuticals, Inc #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to see if pralatrexate extends response and survival following CHOP-based chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) and if pralatrexate improves response in patients with partial response following CHOP-based chemotherapy. Patients will either receive pralatrexate or be under observation. All patients will receive vitamins B12 and folic acid and attend regular clinic visits to evaluate their disease and health. **Detailed Description:** This was an international, multi-center, randomized, Phase 3, open-label study of sequential pralatrexate versus observation in patients with previously undiagnosed PTCL who have achieved an objective response following initial treatment with CHOP-based chemotherapy. Upon documentation of completion of an objective response following at least 6 cycles of a designated CHOP-based chemotherapy confirmation of histopathology by independent review, and confirmation that all eligibility criteria were met, patients were randomized in a 2:1 ratio to either pralatrexate or observation, according to a permuted block design with stratification factor of Tumor Response per Investigator at completion of CHOP-based therapy (Complete Response \[CR\] vs Partial Response \[PR\]). All patients who receive at least 1 dose of pralatrexate were followed for safety through 35 (± 5) days after their last dose of pralatrexate or until all treatment-related AEs have resolved or returned to baseline/Grade 1, whichever is longer, or until it was determined that the outcome does not change with further follow-up. ### Conditions Module **Conditions:** - Peripheral T-cell Lymphoma **Keywords:** - Lymphoproliferative Disorders - Lymphoma - Non-Hodgkin's Lymphoma - T-cell Lymphoma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 21 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients randomized to the Pralatrexate Arm will receive pralatrexate injection and Vitamins B12 and Folic Acid until a criterion for pralatrexate injection treatment discontinuation is met. **Intervention Names:** - Drug: Pralatrexate Injection **Label:** Pralatrexate **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients randomized to the Observation Arm will receive Vitamins B12 and Folic Acid and remain under observation until a criterion for observation discontinuation is met. **Label:** Observation **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Pralatrexate **Description:** Intravenous (IV) push administration over 30 seconds to 5 minutes via a patent IV line containing normal saline (0.9% sodium chloride). Initial dose: 30 mg/m2 Administered weekly for 3 weeks of a 4-week cycle until criteria for discontinuation per the protocol are met. **Name:** Pralatrexate Injection **Other Names:** - FOLOTYN - PDX - Pralatrexate - (RS)-10-propargyl-10-deazaaminopterin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** PFS was defined as the time in days from randomization to the date of objective documentation of progressive disease (PD) or death, regardless of cause (date of PD or death - date of randomization + 1). PFS was to be assessed according to the International Workshop Criteria (IWC) without including positron emission tomography (PET). PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Participants who were alive without a disease response assessment of PD was to be censored at their last disease assessment date or the date of randomization, whichever was later. Date of progression was not to be imputed for participants with missing tumor assessments before an assessment of PD. Participants who withdraw from treatment prior to PD were to be followed for disease status whenever possible. Participants who have no response assessments after baseline were to be censored at randomization. **Measure:** Progression-Free Survival (PFS) **Time Frame:** From randomization to the date of progression of disease or death due to any cause (up to 76 months) **Description:** Overall survival was defined as the time in days from randomization to the date of death, regardless of cause (date of death - date of randomization + 1). **Measure:** Overall Survival (OS) **Time Frame:** From randomization until death (up to 76 months) #### Secondary Outcomes **Description:** Objective response rate was defined as percentage of participants with an objective response of complete response (CR) or partial response (PR), relative to disease status at the time of study entry. The percentage was to be calculated by dividing number of participants within each category of response by the number of participants with measurable disease at baseline. Objective response was assessed according to the IWC without including PET. CR was defined as complete disappearance all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR was defined as regression of measurable disease and no new sites. **Measure:** Objective Response Rate **Time Frame:** Up to 2 years **Description:** An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. AE included both serious and non- SAEs. An AE of "Hematology and Chemistry" was collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening and Grade 4 refers to life-threatening consequences. **Measure:** Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities **Time Frame:** From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient has one of the following peripheral T-cell lymphoma (PTCL) subtypes confirmed by an independent central pathology reviewer, using the Revised European American Lymphoma World Health Organization disease classification: * T/natural killer (NK)-cell leukemia/lymphoma * Adult T-cell lymphoma (TCL)/leukemia (human T-cell leukemia virus 1+) * Angioimmunoblastic TCL * Anaplastic large cell lymphoma (ALCL), primary systemic type, excluding anaplastic lymphoma kinase positive (ALK+) with International Prognostic Index (IPI) score less than 2 at initial diagnosis and complete response (CR) after CHOP-based therapy * PTCL-unspecified * Enteropathy-type intestinal lymphoma * Hepatosplenic TCL * Subcutaneous panniculitis TCL * Transformed mycosis fungoides (tMF) * Extranodal T/NK-cell lymphoma nasal or nasal type * Primary cutaneous gamma-delta TCL * Primary cutaneous CD8+ aggressive epidermic cytotoxic TCL * Documented completion of at least 6 cycles of CHOP-based therapy: * CHOP 21 * CHOP 14 * CHOP + etoposide * Other CHOP variants: substitution allowed for 1 component with a drug of the same mechanism of action. Additional components, except alemtuzumab, are allowed. Rituximab may be added if not given within 3 cycles of randomization. * Patient has achieved CR or partial response (PR) per per investigator's assessment following completion of CHOP-based therapy and has had radiological assessment within 21 days prior to randomization. * Eastern Cooperative Oncology Group performance status less than or equal to 2. * Adequate blood, liver, and kidney function as defined by laboratory tests. * Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate. * Men who are sexually active, including those with a pregnant partner, must agree to practice a medically acceptable barrier method contraceptive regimen (eg, condoms) while receiving pralatrexate and for 90 days after the last administration of pralatrexate. * Has given written informed consent. Exclusion Criteria: * Patient has: * Precursor T/NK neoplasms * ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after CHOP-based therapy * T cell prolymphocytic leukemia * T cell large granular lymphocytic leukemia * Mycosis fungoides, except tMF * Sézary syndrome * Primary cutaneous CD30+ disorders: ALCL and lymphomatoid papulosis * If there is a history of prior malignancies other than those below, must be disease free for at least 5 years. Patients with malignancies listed below less than 5 years before study entry may be enrolled if they have received treatment resulting in complete resolution of the cancer and have no clinical, radiologic, or laboratory evidence of active/recurrent disease. * non-melanoma skin cancer * carcinoma in situ of the cervix * localized prostate cancer * localized thyroid cancer * Receipt of prior chemotherapy (CT) or radiation therapy (RT) for PTCL, other than a single allowed CHOP regimen, except: * Patients with nasal NK lymphoma who received local RT less than 4 weeks prior to randomization. * Patients with tMF who received 1 systemic single-agent CT (except methotrexate) prior to transformation. * Prior exposure to pralatrexate. * Receipt of systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of 10 mg/day or less of oral prednisone or equivalent for at least 4 weeks or as part of a CHOP prednisone taper. * Planned use of any treatment for PTCL during the course of the study. * Patient has: * Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of less than 100 mm3 or detectable viral load within past 3 months and receiving anti-retroviral therapy. * Hepatitis B (HBV)-positive serology and is receiving interferon therapy or has liver function test results outside the parameters of study inclusion criteria. Other antiviral therapies are permitted if at a stable dose for at least 4 weeks. * Hepatitis C (HCV) virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy. * Symptomatic central nervous system metastases or lesions requiring treatment. * Uncontrolled hypertension or congestive heart failure Class III/IV per the New York Heart Association's Heart Failure Guidelines * Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness impairing the ability of the patient to receive protocol treatment. * Major surgery within 2 weeks prior to study entry, except for line placement or biopsy procedure. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Novi **Country:** United States **Facility:** Detroit Clinical Research Center, PC **State:** Michigan **Zip:** 48377 **Location 2:** **City:** New York **Country:** United States **Facility:** New York Presbyterian Hospital **State:** New York **Zip:** 10021 **Location 3:** **City:** New York **Country:** United States **Facility:** Memorial Sloan-Kettering Cancer Center **State:** New York **Zip:** 10065 **Location 4:** **City:** Adelaide **Country:** Australia **Facility:** Royal Adelaide Hospital **State:** South Australia **Zip:** 5000 **Location 5:** **City:** Bedford Park **Country:** Australia **Facility:** Flinders Medical Center **State:** South Australia **Zip:** 5042 **Location 6:** **City:** Hobart **Country:** Australia **Facility:** Royal Hobart Hospital **State:** Tasmania **Zip:** 7001 **Location 7:** **City:** Clayton **Country:** Australia **Facility:** Monash Medical Centre **State:** Victoria **Zip:** 3168 **Location 8:** **City:** Fitzroy **Country:** Australia **Facility:** Saint Vincent's Hospital Melbourne **State:** Victoria **Zip:** 3109 **Location 9:** **City:** Frankston **Country:** Australia **Facility:** Frankston Hospital **State:** Victoria **Zip:** 3199 **Location 10:** **City:** Malvern **Country:** Australia **Facility:** Cabrini Health **State:** Victoria **Zip:** 3144 **Location 11:** **City:** Perth **Country:** Australia **Facility:** Royal Perth Hospital **State:** Western Australia **Zip:** 6000 **Location 12:** **City:** Brugge **Country:** Belgium **Facility:** AZ Sint-Jan **Zip:** 8000 **Location 13:** **City:** Gent **Country:** Belgium **Facility:** Universitair Ziekenhuis Gent **Zip:** 9000 **Location 14:** **City:** Toronto **Country:** Canada **Facility:** Sunnybrook Health Science Centre **State:** Ontario **Zip:** M4N 3M5 **Location 15:** **City:** Montreal **Country:** Canada **Facility:** Hôpital du Sacré-Coeur de Montréal **State:** Quebec **Zip:** H4J 1C5 **Location 16:** **City:** Brest **Country:** France **Facility:** Hôpital Morvan **Zip:** 29609 **Location 17:** **City:** Pessac **Country:** France **Facility:** CHU Haut-Leveque **Zip:** 33604 **Location 18:** **City:** Dublin 8 **Country:** Ireland **Facility:** St James Hospital **Location 19:** **City:** Jerusalem **Country:** Israel **Facility:** Shaare Zedek Medical Center **Zip:** 91031 **Location 20:** **City:** Jerusalem **Country:** Israel **Facility:** Hadassah Ein-Kerem Medical Centre **Zip:** 91120 **Location 21:** **City:** Petach Tikva **Country:** Israel **Facility:** Rabin Medical Center **Zip:** 49100 **Location 22:** **City:** Tel Hashomer **Country:** Israel **Facility:** Chaim Sheba Medical Center **Zip:** 52621 **Location 23:** **City:** Meldola **Country:** Italy **Facility:** Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori **State:** Forli **Zip:** 47014 **Location 24:** **City:** Bologna **Country:** Italy **Facility:** Az. Ospedaliera Universitaria S. Orsola Malpighi **Zip:** 40138 **Location 25:** **City:** Brescia **Country:** Italy **Facility:** Spedali Civili di Brescia **Zip:** 25123 **Location 26:** **City:** Ravenna **Country:** Italy **Facility:** Ospedale S. Maria delle Croci **Zip:** 48121 **Location 27:** **City:** Roma **Country:** Italy **Facility:** Università Cattolica del Sacro Cuore **Zip:** 00168 **Location 28:** **City:** Siena **Country:** Italy **Facility:** Az. Ospedaliera Università Senese **Zip:** 53100 **Location 29:** **City:** Otahuhu **Country:** New Zealand **Facility:** Middlemore Hospital **State:** Auckland **Zip:** 1640 **Location 30:** **City:** Auckland **Country:** New Zealand **Facility:** Auckland City Hospital / Auckland University **Zip:** 1010 **Location 31:** **City:** Christchurch **Country:** New Zealand **Facility:** Christchurch Hospital **Zip:** 8011 **Location 32:** **City:** Milford **Country:** New Zealand **Facility:** North Shore Hospital **Location 33:** **City:** Warszawa **Country:** Poland **Facility:** Klinika Nowotworów Ukladu Chlonnego Centrum Onkologii Instytut Marii Sklodowskiej-Curie **State:** Mazowieckie **Zip:** 02-781 **Location 34:** **City:** Gdansk **Country:** Poland **Facility:** Dept of Hematology and Transplantology **Zip:** 80-952 **Location 35:** **City:** Kraków **Country:** Poland **Facility:** Małopolskie Centrum Medyczne **Zip:** 30-510 **Location 36:** **City:** San Juan **Country:** Puerto Rico **Facility:** Auxilio Mutuo Cancer Center **Zip:** 00918 **Location 37:** **City:** Pamplona **Country:** Spain **Facility:** Clinica Universidad de Navarra **State:** Navarra **Zip:** 31008 **Location 38:** **City:** Pamplona **Country:** Spain **Facility:** Complejo Hospitalario de Navarra, Servicio de Hematologia **State:** Navarra **Zip:** 31008 **Location 39:** **City:** A Coruña **Country:** Spain **Facility:** Complejo Hospitalario Universitario A Coruña- Hospital A Coruña **Zip:** 15006 **Location 40:** **City:** Barcelona **Country:** Spain **Facility:** Hospital General Vall d'Hebron **Zip:** 08035 **Location 41:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Clínic i Provincial de Barcelona **Zip:** 08036 **Location 42:** **City:** Madrid **Country:** Spain **Facility:** Hospital Universitario Ramón y Cajal **Zip:** 28034 **Location 43:** **City:** Madrid **Country:** Spain **Facility:** Hospital de Madrid Norte-Sanchinarro **Zip:** 28050 **Location 44:** **City:** Madrid **Country:** Spain **Facility:** Hospital Universitario Puerta de Hierro Majadahonda **Zip:** 28222 **Location 45:** **City:** Truro **Country:** United Kingdom **Facility:** Royal Cornwall Hospital **State:** Cornwall **Zip:** TR1 3LJ **Location 46:** **City:** Poole **Country:** United Kingdom **Facility:** Poole Hospital NHS Foundation Trust, Poole General Hospital **State:** Dorset **Zip:** BH15 2JB **Location 47:** **City:** Plymouth **Country:** United Kingdom **Facility:** Derriford Hospital **State:** England **Zip:** PL68DH **Location 48:** **City:** West Bromwich **Country:** United Kingdom **Facility:** Sandwell & West Birmingham Hospitals NHS Trust **State:** England **Zip:** B71 4HJ **Location 49:** **City:** Antrim **Country:** United Kingdom **Facility:** Antrim Area Hospital **State:** Northern Ireland **Zip:** BT41 2RL **Location 50:** **City:** Glasgow **Country:** United Kingdom **Facility:** NHS Greater Glasgow and Clyde Western Infirmary **State:** Scotland **Zip:** G11 6NT **Location 51:** **City:** Belfast **Country:** United Kingdom **Facility:** Belfast City Hospital **Zip:** BT9 7AB **Location 52:** **City:** Cardiff **Country:** United Kingdom **Facility:** Velindre Hospital **Zip:** CF14 2TL **Location 53:** **City:** Liverpool **Country:** United Kingdom **Facility:** Royal Liverpool University Hospital **Zip:** L7 8XP **Location 54:** **City:** Middlesex **Country:** United Kingdom **Facility:** Mount Vernon Cancer Centre **Zip:** HA6 2RN **Location 55:** **City:** Warwick **Country:** United Kingdom **Facility:** UHCW (University Hospital Coventry and Warwickshire) **Zip:** CA34 5BW ## Document Section ### Large Document Module #### Large Docs - Date: 2011-10-31 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 14850796 - Type Abbrev: Prot - Upload Date: 2021-10-01T10:27 - Date: 2012-04-18 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 297079 - Type Abbrev: SAP - Upload Date: 2021-10-01T10:28 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000008228 - Term: Lymphoma, Non-Hodgkin ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: HIGH - As Found: Lymphoma - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M18829 - Name: Lymphoma, T-Cell - Relevance: HIGH - As Found: T-cell Lymphoma - ID: M18833 - Name: Lymphoma, T-Cell, Peripheral - Relevance: HIGH - As Found: Peripheral T-cell Lymphoma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M11222 - Name: Lymphoma, Non-Hodgkin - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma - ID: T4496 - Name: Peripheral T-cell Lymphoma - Relevance: HIGH - As Found: Peripheral T-cell Lymphoma ### Condition Browse Module - Meshes - ID: D000008223 - Term: Lymphoma - ID: D000016399 - Term: Lymphoma, T-Cell - ID: D000016411 - Term: Lymphoma, T-Cell, Peripheral ### Intervention Browse Module - Ancestors - ID: D000005493 - Term: Folic Acid Antagonists - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M17548 - Name: Vitamin B 12 - Relevance: LOW - As Found: Unknown - ID: M9934 - Name: Hydroxocobalamin - Relevance: LOW - As Found: Unknown - ID: M237319 - Name: 10-deazaaminopterin - Relevance: HIGH - As Found: Repairing - ID: M3968 - Name: Aminopterin - Relevance: HIGH - As Found: Patient navigator - ID: M8619 - Name: Folic Acid Antagonists - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - Relevance: LOW - As Found: Unknown - ID: T446 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: T451 - Name: Methylcobalamin - Relevance: LOW - As Found: Unknown - ID: T448 - Name: Folate - Relevance: LOW - As Found: Unknown - ID: T475 - Name: Vitamin B9 - Relevance: LOW - As Found: Unknown - ID: T476 - Name: Vitamin B12 - Relevance: LOW - As Found: Unknown - ID: T441 - Name: Cobalamin - Relevance: LOW - As Found: Unknown - ID: T444 - Name: Cyanocobalamin - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000017178 - Term: 10-deazaaminopterin - ID: D000000630 - Term: Aminopterin ### Misc Info Module #### Removed Countries - Country: Austria - Country: Brazil - Country: Bulgaria - Country: Chile - Country: Colombia - Country: Czech Republic - Country: Germany - Country: Hong Kong - Country: Hungary - Country: Korea, Republic of - Country: Mexico - Country: Peru - Country: Romania - Country: Russian Federation - Country: Singapore - Country: Taiwan - Country: Ukraine - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment. #### Event Groups **Group ID:** EG000 **Title:** Pralatrexate Arm **Deaths Num Affected:** 3 **Deaths Num At Risk:** 14 **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. **ID:** EG000 **Other Num Affected:** 14 **Other Num at Risk:** 14 **Serious Number Affected:** 4 **Serious Number At Risk:** 14 **Title:** Pralatrexate Arm **Group ID:** EG001 **Title:** Observation Arm **Deaths Num Affected:** 1 **Deaths Num At Risk:** 7 **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. **ID:** EG001 **Other Num Affected:** 6 **Other Num at Risk:** 7 **Serious Number At Risk:** 7 **Title:** Observation Arm **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Abdominal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Abdominal Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Aphthous stomatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dry mouth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dyspepsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Haematochezia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Haemorrhoids **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Impaired gastric emptying **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Lip ulceration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Oral dysaesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Stomatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Asthenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Face oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Local swelling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Malaise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Mucosal inflammation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Bronchitis Viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Clostridium difficile colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Conjunctivitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Cystitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Diverticulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Fungal infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Rhinitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Viral infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Contusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 **Term:** Foot fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 **Term:** Skull fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 **Term:** Subdural haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 **Term:** Wound **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 17.0 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 17.0 **Term:** Blood alkaline phosphatase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 17.0 **Term:** Body temperature increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 17.0 **Term:** Gammaglutamyltransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 17.0 **Term:** Weight increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 17.0 **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Flank pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Muscle spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Muscular weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Musculoskeletal chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Musculoskeletal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Carotid artery occlusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Convulsion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dysaesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Haemorrhage intracranial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hypokinesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Lethargy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Neuropathy peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Paraesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Sciatica **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** VIIth nerve paralysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Confusional state **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hallucination **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Mental status changes **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dysuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Nocturia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Urinary incontinence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Urinary tract pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dysphonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hiccups **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Nasal congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Oropharyngeal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Pleuritic pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Productive cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Rhinorrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Sneezing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Blister **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Dry skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Eczema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Erythema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hyperhidrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Macule **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Melanosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Nail disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Night sweats **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Onychoclasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Penile ulceration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Pigmentation disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Pruritus generalised **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Rash maculo-papular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Rash pruritic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Skin hyperpigmentation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Skin ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Varicose vein **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Cataract **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Ocular hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Visual acuity reduced **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Endodontic procedure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA 17.0 **Term:** Stent removal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA 17.0 **Term:** Erectile dysfunction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Cardiac arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Sinus bradycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Ichthyosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Skin infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 17.0 **Term:** Decreased appetite/Anorexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Mucosal inflammation/Intermittant Mucositis of Mouth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 **Term:** Disturbance in attention **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 #### Serious Events **Term:** Cardiac arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Stomatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Subdural hematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Haemorrhage intracranial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Carotid artery occlusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** VIIth nerve paralysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Confusional state **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 17.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 14 **Group ID:** EG001 **Num At Risk:** 7 **Time Frame:** From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 14 **Group ID:** BG001 **Value:** 7 **Group ID:** BG002 **Value:** 21 **Units:** Participants ### Group **ID:** BG000 **Title:** Pralatrexate Arm **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. ### Group **ID:** BG001 **Title:** Observation Arm **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 51 **Upper Limit:** 83 **Value:** 72.0 #### Measurement **Group ID:** BG001 **Lower Limit:** 44 **Upper Limit:** 83 **Value:** 61.0 #### Measurement **Group ID:** BG002 **Lower Limit:** 44 **Upper Limit:** 83 **Value:** 68.0 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 8 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 13 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Black #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Arabic #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 15 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Missing **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** The study was prematurely terminated due to business reasons. There were no safety concerns that led to study closure. No efficacy assessments and analysis was conducted. A full statistical analysis and report were not completed. ### Point of Contact **Email:** gajanan.Bhat@sppirx.com **Organization:** Spectrum Pharmaceuticals, Inc **Phone:** 949-743-9219 **Title:** Gajanan Bhat ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** Median and 95% CI were not estimable due to low number of participants with events. - **Group ID:** OG000 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Median and 95% CI were not estimable due to low number of participants with events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 3 #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** PFS was defined as the time in days from randomization to the date of objective documentation of progressive disease (PD) or death, regardless of cause (date of PD or death - date of randomization + 1). PFS was to be assessed according to the International Workshop Criteria (IWC) without including positron emission tomography (PET). PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Participants who were alive without a disease response assessment of PD was to be censored at their last disease assessment date or the date of randomization, whichever was later. Date of progression was not to be imputed for participants with missing tumor assessments before an assessment of PD. Participants who withdraw from treatment prior to PD were to be followed for disease status whenever possible. Participants who have no response assessments after baseline were to be censored at randomization. **Population Description:** Data for this outcome measure was not collected and analyzed due to the early termination of the study. **Reporting Status:** POSTED **Time Frame:** From randomization to the date of progression of disease or death due to any cause (up to 76 months) **Title:** Progression-Free Survival (PFS) **Type:** PRIMARY ##### Group **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. **ID:** OG000 **Title:** Pralatrexate Arm ##### Group **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. **ID:** OG001 **Title:** Observation Arm #### Outcome Measure 2 **Description:** Overall survival was defined as the time in days from randomization to the date of death, regardless of cause (date of death - date of randomization + 1). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** ITT population included all randomized participants classified according to the treatment arms into which they were randomized, regardless of the actual study treatment received (or not received). **Reporting Status:** POSTED **Time Frame:** From randomization until death (up to 76 months) **Title:** Overall Survival (OS) **Type:** PRIMARY **Unit of Measure:** months ##### Group **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. **ID:** OG000 **Title:** Pralatrexate Arm ##### Group **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. **ID:** OG001 **Title:** Observation Arm #### Outcome Measure 3 **Description:** Objective response rate was defined as percentage of participants with an objective response of complete response (CR) or partial response (PR), relative to disease status at the time of study entry. The percentage was to be calculated by dividing number of participants within each category of response by the number of participants with measurable disease at baseline. Objective response was assessed according to the IWC without including PET. CR was defined as complete disappearance all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR was defined as regression of measurable disease and no new sites. **Population Description:** Data for this outcome measure was not collected and analyzed due to early termination of the study. **Reporting Status:** POSTED **Time Frame:** Up to 2 years **Title:** Objective Response Rate **Type:** SECONDARY ##### Group **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. **ID:** OG000 **Title:** Pralatrexate Arm ##### Group **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. **ID:** OG001 **Title:** Observation Arm #### Outcome Measure 4 **Description:** An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. AE included both serious and non- SAEs. An AE of "Hematology and Chemistry" was collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening and Grade 4 refers to life-threatening consequences. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment. **Reporting Status:** POSTED **Time Frame:** From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) **Title:** Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. **ID:** OG000 **Title:** Pralatrexate Arm ##### Group **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. **ID:** OG001 **Title:** Observation Arm ### Participant Flow Module #### Group **Description:** Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years. **ID:** FG000 **Title:** Pralatrexate Arm #### Group **Description:** Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met. **ID:** FG001 **Title:** Observation Arm #### Period **Title:** Overall Study ##### Withdraw **Type:** Disease Progression ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** More Than 28 Days Between Doses of Drug ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Patient Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Investigator Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Sponsor Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 7 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 7 **Pre-Assignment Details:** A total of 21 participants with peripheral T-cell lymphoma (PTCL) were randomized in 2:1 ratio to Pralatrexate arm or Observation arm. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03518879 **Brief Title:** ASTHMA-Educator Mobile Application Manage Asthma **Official Title:** The ASTHMA-Educator: A Novel Algorithmic Software Tool to Help Manage Asthma #### Organization Study ID Info **ID:** 2013-2693 #### Organization **Class:** OTHER **Full Name:** Montefiore Medical Center ### Status Module #### Completion Date **Date:** 2021-07-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-07 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-07-01 **Type:** ACTUAL #### Start Date **Date:** 2015-03 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2018-05-08 **Type:** ACTUAL **Study First Submit Date:** 2018-04-13 **Study First Submit QC Date:** 2018-04-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Montefiore Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Through this study, the investigators developed the ASTHMA-Educator mobile application, and evaluated its use among adult asthma patients at Montefiore. **Detailed Description:** Through this study, the investigators developed the ASTHMA-Educator mobile application, and evaluated its use through 2 phases: 1) Phase 1 = process outcomes evaluation with 30 patients); and 2) Phase 2 (longitudinal clinical evaluation with 40 patients receiving the intervention at baseline, 2 months, 4 months, and 6 months). The study's primary outcome is asthma control. ### Conditions Module **Conditions:** - Asthma **Keywords:** - informatics - asthma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** This is a single-arm proof of concept study to evaluate the impact of the ASTHMA-Educator on process and clinical outcomes ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 70 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The ASTHMA-Educator mobile application for patient-centered asthma education. The application is administered via on-site iPad (tablet). **Intervention Names:** - Other: ASTHMA-Educator mobile application **Label:** ASTHMA-Educator arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - ASTHMA-Educator arm **Description:** The on-site delivered ASTHMA-Educator mobile application. **Name:** ASTHMA-Educator mobile application **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Asthma symptom burden as measured by the Asthma Control Test **Measure:** Change from baseline asthma control to 2, 4, and 6 months **Time Frame:** Baseline, 2 months, 4 months, 6 months #### Secondary Outcomes **Description:** Asthma knowledge as measured by the validated Asthma Knowledge Questionnaire **Measure:** Change from baseline asthma knowledge to immediately post-intervention, 2 months, 4 months, and 6 months **Time Frame:** Baseline, immediately post-intervention, 2 months, 4 months, 6 months **Description:** Patient satisfaction measured by the Client Satisfaction Questionnaire-8 **Measure:** Patient satisfaction measured by the Client Satisfaction Questionnaire-8 **Time Frame:** Immediately post-intervention at the baseline visit, 2 months, 4 months, 6 months **Description:** Time spent in using the mobile application **Measure:** Time spent in using the mobile application **Time Frame:** Immediately post-intervention at the baseline visit **Description:** Patients' asthma quality of life measured by the mini-Asthma Quality of Life Questionnaire (mini-AQLQ) **Measure:** Asthma quality of life measured by the mini-Asthma Quality of Life Questionnaire (mini-AQLQ) **Time Frame:** Baseline, 2 months, 4 months, 6 months **Description:** Asthma emergency department visits **Measure:** Asthma emergency department visits **Time Frame:** Baseline, 2 months, 4 months, 6 months **Description:** Asthma hospitalizations **Measure:** Asthma hospitalizations **Time Frame:** Baseline, 2 months, 4 months, 6 months **Description:** Asthma-related steroid courses **Measure:** Asthma-related steroid courses **Time Frame:** Baseline, 2 months, 4 months, 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Adults (\>18 years) with: (a) severe asthma (i.e. at least one asthma-related ED visit and/or hospitalization in the previous year); (b) access to a smartphone with short message service (SMS) capability; (c) English speaking; (d) able to give informed consent. Exclusion Criteria: (a) use of oral corticosteroids in the 2 weeks prior to the baseline visit; (b) pregnancy; (c) severe psychiatric or cognitive problems that would prohibit an individual from understanding and completing the protocol; and (d) patients that previously received the ASTHMAXcel application. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bronx **Country:** United States **Facility:** Montefiore Medical Center **State:** New York **Zip:** 10467 #### Overall Officials **Official 1:** **Affiliation:** Montefiore Medical Center **Name:** Sunit Jariwala **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** The investigators will share de-identified and aggregated study findings. **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001982 - Term: Bronchial Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000008171 - Term: Lung Diseases - ID: D000012130 - Term: Respiratory Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4556 - Name: Asthma - Relevance: HIGH - As Found: Asthma - ID: M5258 - Name: Bronchial Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14967 - Name: Respiratory Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001249 - Term: Asthma ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01061879 **Brief Title:** Expansion of Umbilical Cord Blood Using a Unique Bio-system **Official Title:** Ex Vivo Expansion of Umbilical Cord Blood Using a Unique Bio-system #### Organization Study ID Info **ID:** 11973 #### Organization **Class:** OTHER **Full Name:** University of Kansas Medical Center ### Status Module #### Completion Date **Date:** 2010-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-01-03 **Type:** ESTIMATED **Last Update Submit Date:** 2012-12-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-11 **Type:** ACTUAL #### Start Date **Date:** 2010-02 **Status Verified Date:** 2012-12 #### Study First Post Date **Date:** 2010-02-03 **Type:** ESTIMATED **Study First Submit Date:** 2010-02-02 **Study First Submit QC Date:** 2010-02-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Kansas #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** By doing this study, researchers hope to develop a special technique and laboratory conditions to help support umbilical stem cell growth and multiplication. In this project, researchers propose a three dimensional (3D) microenvironment that mimics the bone marrow stem cell microenvironment, with its supporting cells of osteoblasts and stromal cells. In theory, this will result in better expansion of cord blood stem cells ex vivo. **Detailed Description:** To successfully expand umbilical cord blood stem cells ex vivo, a microenvironment that resembles the stem cell microenvironment, or stem cell 'niche' should be created. In designing this bio-system, we make use of several observations. First, bone osteoblasts are important in promoting hematopoietic stem cell expansion, accordingly, this bio-system will ensure the physical proximity of the cord blood stem cells to a 3D bone tissue derived from mesenchymal stem cells (MSCs). These MSCs will be isolated from Wharton's jelly, and by using an osteogenic medium and special scaffolds, these MSCs will differentiate into osteogenic progenitors creating a 3D bone structure. The other observation is that, co-culture of cord blood stem cells with mesenchymal stem cells is superior to liquid cultures in terms of ex vivo expansion , accordingly, in this experiment, undifferentiated MSCs will be co-cultured with cord blood stem cells in this created 3D bone structure. This is a unique design that has the potential to expand cord blood stem cells more efficiently. ### Conditions Module **Conditions:** - Pregnancy **Keywords:** - umbilical cord - umbilical cord blood collection - pregnancy ### Design Module #### Bio Spec **Description:** umbilical cord **Retention:** SAMPLES_WITH_DNA #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** To successfully expand the umbilical cord blood stem cells, a microenvironment that resembles the stem cell microenvironment, or stem cell 'niche' should be created. In designing this bio-system, we make use of several observations. Firstly, bone osteoblasts are important in promoting hematopoietic stem cell expansion , accordingly, this bio-system will ensure the physical proximity of the cord blood stem cells to a 3D bone tissue derived from mesenchymal stem cells (MSCs). These MSCs will be isolated from Wharton's jelly, and by using an osteogenic medium and special scaffolds, these MSCs will differentiate into osteogenic progenitors creating a 3D bone structure . The other observation is that, co-culture of cord blood stem cells with mesenchymal stem cells is superior to liquid cultures in terms of ex vivo expansion , accordingly, in this experiment, undifferentiated MSCs will be co-cultured with cord blood stem cells in the created 3D bone structure. **Measure:** bio-system for ex-vivo expansion of umbilical cord blood stem cells **Time Frame:** one year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * females that consent to permit researchers collect the discarded umbilical cords from the placenta and use for research purposes. Exclusion Criteria: - **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** umbilical cord collection from full-term caesarian section/normal vaginal delivery patients ### Contacts Locations Module #### Locations **Location 1:** **City:** Kansas City **Country:** United States **Facility:** University of Kansas Medical Center **State:** Kansas **Zip:** 66160 #### Overall Officials **Official 1:** **Affiliation:** University of Kansas Medical Center **Name:** Omar Aljitawi, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01329679 **Brief Title:** Impact of Energy Drinks on Cardiovascular Endpoints **Official Title:** Effects of Single and Multiple Energy Shots on Blood Pressure and Electrocardiographic Parameters: A Randomized, Double Blind, Crossover, Placebo-controlled Trial #### Organization Study ID Info **ID:** FWH20110111H #### Organization **Class:** FED **Full Name:** David Grant U.S. Air Force Medical Center ### Status Module #### Completion Date **Date:** 2013-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-09-09 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-24 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2013-07 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-01-10 **Type:** ESTIMATED **Results First Submit Date:** 2016-08-29 **Results First Submit QC Date:** 2016-11-13 #### Start Date **Date:** 2011-04 **Type:** ACTUAL **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2011-04-06 **Type:** ESTIMATED **Study First Submit Date:** 2011-04-04 **Study First Submit QC Date:** 2011-04-05 **Why Stopped:** Unable to recruit enough subjects ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** David Grant U.S. Air Force Medical Center #### Responsible Party **Investigator Affiliation:** David Grant U.S. Air Force Medical Center **Investigator Full Name:** Sachin Shah **Investigator Title:** Assistant Professor of Pharmacy Practice **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Objective: To assess the cardiac effects of a an energy drink on blood pressure and heart rhythm in healthy subjects. Study design: Double blind, placebo controlled, cross-over Study population: Healthy human volunteers (active-duty) between age 18 to 40 years with no other medical conditions. Intervention: Energy drink or Placebo Primary outcome: Change in office systolic blood pressure ### Conditions Module **Conditions:** - Healthy Volunteers ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** OTHER #### Enrollment Info **Count:** 26 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Energy drink, 2 oz twice daily for 7 days **Intervention Names:** - Dietary Supplement: Energy Drink **Label:** Energy Drink **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Water, lime juice and cherry flavoring, 2 oz twice daily for 7 days **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Energy Drink **Description:** Energy drink, 2oz twice daily for 7 days **Name:** Energy Drink **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Water, lime juice and cherry flavoring **Name:** Placebo **Other Names:** - Water, lime juice and cherry flavoring **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** SBP = Systolic Blood Pressure measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days. **Measure:** Change in Office Systolic Blood Pressure **Time Frame:** At baseline and 7 days post energy drink and placebo consumption #### Secondary Outcomes **Description:** DBP = Diastolic Blood Pressure measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days. **Measure:** Office DBP After a Single Energy Shot and After Chronic Consumption **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Description:** Maximum heart rate measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Measure:** Max Heart Rate After a Single Shot and After Chronic Consumption **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Description:** Maximum PR-interval measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Measure:** Max PR-interval After a Single Shot and After Chronic Consumption **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Description:** Max QRS duration measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Measure:** Max QRS Duration After a Single Shot and After Chronic Consumption **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Description:** Max QT interval measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Measure:** Max QT Interval After a Single Energy Shot or Placebo Consumption After Day 1 and After Chronic Consumption After Day 7 **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Description:** Max QTc interval measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Measure:** Max QTc Interval After a Single Energy Shot or Placebo Consumption After Day 1 and After Chronic Consumption After Day 7 **Time Frame:** At baseline and 7 days post energy drink and placebo consumption ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy volunteers between ages 18-40 years * ONLY "as needed" use of ibuprofen or acetamenophen * Active duty military * DoD beneficiary or Civilian Government Employees Exclusion Criteria: * No other co-morbid conditions * No active prescription or OTC drug use * Not pregnant or planning to become pregnant during study participation **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** David Grant Medical Center **Name:** Shah Sachin, Pharm.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module #### Removed Countries - Country: United States - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Energy Drink **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days **ID:** EG000 **Other Num at Risk:** 26 **Serious Number At Risk:** 26 **Title:** Energy Drink **Group ID:** EG001 **Title:** Placebo **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** EG001 **Other Num at Risk:** 26 **Serious Number At Risk:** 26 **Title:** Placebo **Frequency Threshold:** 0 **Time Frame:** During the study, for up to 7 days per intervention ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 26 **Units:** Participants ### Group **ID:** BG000 **Title:** All Study Participants **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days Placebo: Water, lime juice and cherry flavoring ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 26 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 5.77 **Value:** 28.3 **Class Title:** Age ### Measure #### Measurement **Group ID:** BG000 **Value:** 6 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 20 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 **Class Title:** Caucasian #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** African American #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** Hispanic ### Measure #### Measurement **Group ID:** BG000 **Value:** 26 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** Small sample size and limited to 7 days of consumption. ### Point of Contact **Email:** sshah@pacific.edu **Organization:** DavidGrant **Phone:** 707-423-3277 **Title:** Sachin Shah ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.98 - **Upper Limit:** - **Value:** 128 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.49 - **Upper Limit:** - **Value:** 123 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.88 - **Upper Limit:** - **Value:** 127 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.29 - **Upper Limit:** - **Value:** 124 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.79 - **Upper Limit:** - **Value:** 82.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.80 - **Upper Limit:** - **Value:** 79.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.84 - **Upper Limit:** - **Value:** 82.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.33 - **Upper Limit:** - **Value:** 78.7 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.50 - **Upper Limit:** - **Value:** 69.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.41 - **Upper Limit:** - **Value:** 70.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.21 - **Upper Limit:** - **Value:** 68.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.7 - **Upper Limit:** - **Value:** 67 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.8 - **Upper Limit:** - **Value:** 166 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.3 - **Upper Limit:** - **Value:** 161 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15 - **Upper Limit:** - **Value:** 164 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 16.7 - **Upper Limit:** - **Value:** 164 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.18 - **Upper Limit:** - **Value:** 92.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.26 - **Upper Limit:** - **Value:** 92.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.5 - **Upper Limit:** - **Value:** 94.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.76 - **Upper Limit:** - **Value:** 93.4 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 21.9 - **Upper Limit:** - **Value:** 414 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 16.2 - **Upper Limit:** - **Value:** 412 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 21.2 - **Upper Limit:** - **Value:** 422 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 21 - **Upper Limit:** - **Value:** 418 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.3 - **Upper Limit:** - **Value:** 422 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18 - **Upper Limit:** - **Value:** 424 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20.1 - **Upper Limit:** - **Value:** 426 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 21.5 - **Upper Limit:** - **Value:** 419 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** SBP = Systolic Blood Pressure measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Change in Office Systolic Blood Pressure **Type:** PRIMARY **Unit of Measure:** mmHg ##### Group **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** DBP = Diastolic Blood Pressure measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Office DBP After a Single Energy Shot and After Chronic Consumption **Type:** SECONDARY **Unit of Measure:** mmHg ##### Group **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** Maximum heart rate measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Max Heart Rate After a Single Shot and After Chronic Consumption **Type:** SECONDARY **Unit of Measure:** beats per minute ##### Group **Description:** Energy drink: Energy drink, 2 oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Description:** Maximum PR-interval measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Max PR-interval After a Single Shot and After Chronic Consumption **Type:** SECONDARY **Unit of Measure:** msec ##### Group **Description:** Energy drink, 2oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Description:** Max QRS duration measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Max QRS Duration After a Single Shot and After Chronic Consumption **Type:** SECONDARY **Unit of Measure:** msec ##### Group **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Description:** Max QT interval measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Max QT Interval After a Single Energy Shot or Placebo Consumption After Day 1 and After Chronic Consumption After Day 7 **Type:** SECONDARY **Unit of Measure:** msec ##### Group **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Description:** Max QTc interval measured at baseline (after a single energy shot or placebo consumption) and after chronic consumption for 7 days **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At baseline and 7 days post energy drink and placebo consumption **Title:** Max QTc Interval After a Single Energy Shot or Placebo Consumption After Day 1 and After Chronic Consumption After Day 7 **Type:** SECONDARY **Unit of Measure:** msec ##### Group **Description:** Energy drink: Energy drink, 2oz twice daily for 7 days **ID:** OG000 **Title:** Energy Drink ##### Group **Description:** Placebo: Water, lime juice and cherry flavoring **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Energy drink, 2 oz twice daily for 7 days, washout period, then Placebo: Water, lime juice and cherry flavoring **ID:** FG000 **Title:** Energy Drink, Then Placebo #### Group **Description:** Placebo: Water, lime juice and cherry flavoring, 2 oz twice daily for 7 days, washout period, then energy drink, 2 oz twice daily for 7 days **ID:** FG001 **Title:** Placebo, Then Energy Drink #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 13 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 13 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01971879 **Acronym:** PARADIS **Brief Title:** Protection of Arteritic Patients by Remote Preconditioning **Official Title:** Protection of Arteritic Patients by Remote Preconditioning #### Organization Study ID Info **ID:** AOI 2012-07 #### Organization **Class:** OTHER_GOV **Full Name:** University Hospital, Angers ### Status Module #### Completion Date **Date:** 2013-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2013-10-29 **Type:** ESTIMATED **Last Update Submit Date:** 2013-10-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2013-12 **Type:** ESTIMATED #### Start Date **Date:** 2013-10 **Status Verified Date:** 2013-10 #### Study First Post Date **Date:** 2013-10-29 **Type:** ESTIMATED **Study First Submit Date:** 2013-10-17 **Study First Submit QC Date:** 2013-10-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** University Hospital, Angers #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Prospective, monocentric, randomised, double-blind study with 20 patients enrolled to be explored twice through a Cross-over strategy to determine whether remote preconditioning improves arteritic patients' ability to walk. **Detailed Description:** Patients will be screened amongst arteritic patients who have undergone a positive treadmill test in Angers University Hospital, defined by a premature test stop caused by muscular pain associated to trans-cutaneous pressure of oxygen (TCPO2) drop. After signing the informed consent, patients will take two treadmill tests in a week-span. According to randomization, patients will undergo the "remote preconditioning" procedure or the "control" procedure before the first treadmill test. The following week, in respect to a cross-over strategy patients will undergo the other procedure before the second treadmill test. Only the study nurse will be advised of the procedure to do. Investigators will not be informed about the allocated procedure. Patients will not be informed about the procedure supposed to have a beneficial effect. The treadmill test will be run according to a calibrated protocol. After a 2-minute stand-up resting period, the treadmill will progressively speed up to a 3.2km/h during one minute. This stage will be maintained with a 10% slope for 14 minutes. Then, the treadmill's slope and speed will increase progressively every minute according to a calibrated protocol. The test duration will be measured from the start of the walk to the patient's request to stop because of pain in the lower limbs. TCPO2 will be measured before and during the test on the glutei and the legs. Tissue oxygenation on both lower limbs will be measured by Near Infra-Red Spectroscopy (NIRO-200NX system). Oxygen consumption will be analysed throughout the test. A blood sample will be drawn just before the start of the test, that is 5 minutes after the end of the last cuff deflation. A second blood sample will be drawn 2 minutes after the patient's request to stop walking. These blood samples are composed of one 3ml tube to measure out blood lactate level, one 6ml ethylene diamine tetraacetic acid (EDTA) tube and a 5ml plain tube. These two last tubes will be centrifuged and subsampled to build up a bio-collection stored at the local Biological Resources Center. ### Conditions Module **Conditions:** - Obliterating Arteriopathy of the Lower Limbs **Keywords:** - Remote ischemic preconditioning - Obliterating Arteriopathy of the Lower Limbs ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: Control **Label:** Control **Type:** SHAM_COMPARATOR #### Arm Group 2 **Intervention Names:** - Procedure: Remote ischemic preconditioning **Label:** Remote preconditioning **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Remote preconditioning **Description:** A blood pressure cuff is placed on one arm and is inflated to 200mmHg during 5 minutes. During the following 5 minutes, the cuff is inflated at the same pressure on the contralateral arm. This sequence is repeated 3 times, that is to say 3 sequences of cuff inflation for 5 minutes on each arm followed by 5 minutes without inflation. The treadmill test starts 5 minutes after the end of the last deflation of the cuff. **Name:** Remote ischemic preconditioning **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Control **Description:** A blood pressure cuff is placed on one arm and is inflated to 10mmHg during 5 minutes. During the following 5 minutes, the cuff is inflated at the same pressure on the contralateral arm. This sequence is repeated 3 times, that is to say 3 sequences of cuff inflation for 5 minutes on each arm followed by 5 minutes without inflation. The treadmill test starts 5 minutes after the end of the last deflation of the cuff. **Name:** Control **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Walking distance during the calibrated treadmill test **Time Frame:** 1 week #### Secondary Outcomes **Measure:** Tissue oxygenation measure by Near Infra-Red Spectroscopy during the test **Time Frame:** 1 week **Measure:** TCPO2 half-rise time measure after the test **Time Frame:** 1 week **Measure:** Measure of the deepness of TCPO2 drop **Time Frame:** 1 week **Measure:** Heart rate measured 1 min and 2 min after test stop/ resting heart rate before test **Time Frame:** 1 week **Measure:** Oxygen consumption analyse during the effort (VO2) **Time Frame:** 1 week **Measure:** Lactate blood level at the end of the test **Time Frame:** 1 week ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Positive treadmill test (maximum walking distance \< 750m because of lower limbs muscular pain) * Resting systolic pressure index \< 0,9 (uni- or bilateral) * Resting systolic blood pressure \<200mmHg * Written informed consent * Affiliation to a Social Security scheme Exclusion Criteria: * Effort hypoxemia during the selection treadmill test * Patient treated with metformin during the 7 days preceding the treadmill tests * Person who is not affiliated to a Social Security scheme or benefiting from such a scheme * Person in an exclusion period related to another biomedical study * Patient refusal / patient not having provided written informed consent **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** faprunier@chu-angers.fr **Name:** Fabrice PRUNIER, Professor **Phone:** +33241.355.147 **Role:** CONTACT #### Locations **Location 1:** **City:** Angers **Contacts:** ***Contact 1:*** - **Email:** PiAbraham@chu-angers.fr - **Name:** Pierre ABRAHAM, Professor - **Phone:** +33241.356.689 - **Role:** CONTACT ***Contact 2:*** - **Name:** Sylvain GRALL, Doctor - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Pierre ABRAHAM, Professor - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Antoine BRUNEAU, Doctor - **Role:** SUB_INVESTIGATOR **Country:** France **Facility:** Service de Médecine du Sport, CHU d'Angers **Status:** RECRUITING **Zip:** 49000 #### Overall Officials **Official 1:** **Affiliation:** University Hospital, Angers **Name:** Fabrice PRUNIER, Professor **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** University Hospital, Angers **Name:** Sylvain GRALL, Doctor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00643279 **Brief Title:** Chronicle Offers Management to Patients With Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) **Official Title:** Chronicle Offers Management to Patients With Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) #### Organization Study ID Info **ID:** COMPASS-HF #### Organization **Class:** INDUSTRY **Full Name:** Medtronic Cardiac Rhythm and Heart Failure ### Status Module #### Completion Date **Date:** 2013-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-22 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2005-06 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-09-16 **Type:** ACTUAL **Results First Submit Date:** 2019-06-11 **Results First Submit QC Date:** 2019-08-13 #### Start Date **Date:** 2003-03 **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2008-03-26 **Type:** ESTIMATED **Study First Submit Date:** 2008-02-29 **Study First Submit QC Date:** 2008-03-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Medtronic Cardiac Rhythm and Heart Failure #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** COMPASS-HF was a prospective, two-arm, randomized (1:1), multi-center, parallel controlled study. The purpose of the randomized study was to test the safety of an implantable hemodynamic monitor (IHM) and pressure sensor lead. The premise of this study was to compare the effectiveness of a novel heart failure management strategy based on information obtained from the IHM system in reducing heart failure morbidity compared to a strategy based on standard medical care alone. **Detailed Description:** COMPASS-HF was a prospective, two-arm, randomized (1:1), multi-center, parallel controlled study. The purpose of the randomized study was to test the safety of an implantable hemodynamic monitor (IHM) and pressure sensor lead. The premise of this study was to compare the effectiveness of a novel heart failure management strategy based on information obtained from the IHM system in reducing heart failure morbidity compared to a strategy based on standard medical care alone. After baseline evaluation and verification that entrance criteria were met, all subjects were implanted with a Chronicle IHM and pressure sensor lead. Following successful implantation, subjects were randomized to either the CHRONICLE group or CONTROL group. Subjects randomized to the CHRONICLE group were managed using Chronicle, specifically trended RV and estimated PA pressure, heart rate and activity data, whereas subjects randomized to the CONTROL group were treated conventionally without the use of the Chronicle data. In the case that implantation was not successful, subjects were exited from the study if no procedure related adverse events were identified; procedure related adverse events were followed through to resolution before the subject were withdrawn from the study. Subjects remained randomized until their six month clinic visit had been completed. Following the subject's six month visit, clinicians were granted access to the CONTROL subject's trended Chronicle data on the Chronicle website, and subjects were seen in the clinic for a protocol-required visit every six months until exit from the study. ### Conditions Module **Conditions:** - Heart Failure **Keywords:** - implantable hemodynamic monitor - Intracardiac pressures ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 277 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects randomized to the CHRONICLE group were managed using data from an implantable hemodynamic monitoring (IHM) device, including trended right ventricular (RV) and estimated pulmonary arterial (PA) pressures, heart rate and activity data. The Chronicle IHM device does not provide therapy, but rather provides intracardiac diagnostic information about the patient which the physician can utilize to manage the patient and the patients heart failure. **Intervention Names:** - Device: Chronicle Implantable Hemodynamic Monitor **Label:** CHRONICLE **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects randomized to the CONTROL group implanted with the Chronicle implantable hemodynamic monitoring (IHM) device, but the intracardiac diagnostic information was blinded to both the patient and the physician during the randomized period of the study. Subjects were managed conventionally with standard of care. Physicians and patients have access to the intracardiac data after the randomized period of the study is over, at 6 months. **Intervention Names:** - Other: Standard of Care **Label:** CONTROL **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - CHRONICLE **Description:** Surgical implantation of chronic ambulatory implantable hemodynamic monitoring (IHM) device and intracardiac pressure sensing lead. The implantable hemodynamic monitoring device captures intracardiac hemodynamic information about the patient including trended right ventricular (RV) and estimated pulmonary arterial (PA) pressures, heart rate and activity data. The IHM device does not provide therapy, but rather provides intracardiac diagnostic information about the patient which the physician can utilize to manage the patient and the patients heart failure. **Name:** Chronicle Implantable Hemodynamic Monitor **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - CONTROL **Description:** Surgical implantation of chronic ambulatory implantable hemodynamic monitoring (IHM) device and intracardiac pressure sensing lead, but physician and patient access to the intracardiac information provided by the device is restricted until the end of the randomized period of the study, at 6 months. Patients and patients heart failure are managed conventionally per standard of care. **Name:** Standard of Care **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** A Chronicle IHM system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death, (3) results in the explant of any Chronicle IHM component, and/or (4) causes permanent loss of significant function of the implanted system. Safety is defined as ≥ 80% of participants experiencing freedom from device related complications through 6 months. **Measure:** Safety as Measured by the Percentage of Participants Free From System Related Complications Through 6 Months. **Time Frame:** Within 6 months post-implant **Description:** A pressure sensor failure was defined as a recognizable, abrupt, non-physiologic shift in pressure parameters. Safety is defined as ≥ 90% of participants free from pressure sensor lead failure through 6 months. **Measure:** Safety as Measured by the Percentage of Participants Free From Implantable Hemodynamic Monitor Pressure Related Sensor Lead Failures Through 6 Months. **Time Frame:** Within 6 months post-implant **Description:** Hospital equivalents (HE) were defined to include the following events: 1. Heart failure-related hospital admissions for 24 hours or longer 2. Heart failure-related emergency department visits and necessitates invasive treatment (e.g. IV diuretic administration). 3. Heart failure-related urgent visits and necessitates invasive treatment (e.g. IV diuretic administration). **Measure:** Rate of Heart Failure-related Hospital Equivalents. **Time Frame:** 6 Months post-implant #### Secondary Outcomes **Description:** Characterize total health care utilization, the total number of all-cause hospitalization, emergency department, and urgent care visits. **Measure:** Health Care Utilization **Time Frame:** 6 Months post-implant **Description:** The number of days alive outside the hospital was calculated as the number of days of randomized follow-up minus the number of days hospitalized during the randomized follow-up period. **Measure:** Days Hospitalization Free **Time Frame:** 6 Months post-implant **Description:** Worsened, Improved and Unchanged were defined as follows: Worsened: Patient died, hospitalized for worsening heart failure, worsened NYHA Class Improved: Patient improved in NYHA Class Unchanged: Patient was neither improved nor worsened. **Measure:** Clinical Composite Response of Either "Worsened", "Improved", or "Unchanged" **Time Frame:** 6 Months post-implant **Description:** Quality of life was measured by the Minnesota Living with Heart Failure (MLHF), a questionnaire with 21 questions and scored on a scale from 0 (good quality of life) to 105 (low quality of life). Change in quality of life is defined as change from baseline to month 6. A participant must have completed a quality of life survey at the baseline visit and month 6 visit to be included in the analysis. **Measure:** Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire **Time Frame:** 6 Months post-implant **Description:** New York Heart Association (NYHA) Classifications were defined as follows: Class I - Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or angina. Class II - Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or angina. Class III - Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or angina. Class IV - Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. **Measure:** New York Heart Association (NYHA) Class **Time Frame:** 6 Months post-implant **Description:** Patients completed six minute hall walk at baseline and 6 months. Outcome is change in hall walk distance from baseline to 6 months. **Measure:** Distance Walked During a Six Minute Hall Walk **Time Frame:** 6 Months post-implant ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects with heart failure classified as New York Heart Association (NYHA) Class III and IV * Subject has been managed with standard medical therapy for heart failure (such as diuretic, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB), and beta-blocker for at least 3 months prior to the baseline evaluation * Subject must have at least one heart failure-related hospitalization or emergency department visit requiring intravenous treatment within 6 months prior to baseline evaluation Exclusion Criteria: * Subjects who are likely to be transplanted within 6 months from randomization or will remain hospitalized until transplantation * Subjects with severe COPD or restrictive airway disease (recommended FEV1 less than or equal to 1 liter or 50% predicted) * Subjects who are on continuous positive inotropic therapy * Subjects with known atrial or ventricular septal defects * Subjects with mechanical right heart valves * Subjects with stenotic tricuspid or pulmonary valves * Subjects with a presently implanted non-compatible pacemaker or ICD * Subjects with cardiac resynchronization therapy which has not achieved optimal programming for more than 3 months * Subjects with a major cardiovascular event within 3 months prior to baseline evaluation * Subjects with a severe non-cardiac condition limiting 6 month survival * Subjects with a primary diagnosis of pulmonary artery hypertension * Subjects with serum creatinine greater than or equal to 3.5 mg/dL or on chronic renal dialysis * Subjects enrolled in concurrent studies that may confound the results of this study * Women who are pregnant or with child bearing potential and who are not on a reliable form of birth control **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham **State:** Alabama **Location 2:** **City:** Loma Linda **Country:** United States **Facility:** Loma Linda University Medical Center **State:** California **Location 3:** **City:** Los Angeles **Country:** United States **Facility:** UCLA Medical Center **State:** California **Location 4:** **City:** Los Angeles **Country:** United States **Facility:** University of Southern California **State:** California **Location 5:** **City:** Gainesville **Country:** United States **Facility:** University of Florida - Shands **State:** Florida **Location 6:** **City:** Atlanta **Country:** United States **Facility:** Crawford LongHospital **State:** Georgia **Location 7:** **City:** Springfield **Country:** United States **Facility:** Prairie Heart Institute **State:** Illinois **Location 8:** **City:** Fort Wayne **Country:** United States **Facility:** Parkview Memorial Hospital **State:** Indiana **Location 9:** **City:** Boston **Country:** United States **Facility:** New England Medical Center **State:** Massachusetts **Location 10:** **City:** Saint Paul **Country:** United States **Facility:** St. Paul Heart **State:** Minnesota **Location 11:** **City:** Kansas City **Country:** United States **Facility:** Mid America Heart Institute **State:** Missouri **Location 12:** **City:** New Brunswick **Country:** United States **Facility:** Robert Wood Johnson Medical Center **State:** New Jersey **Location 13:** **City:** Newark **Country:** United States **Facility:** Newark Beth Israel **State:** New Jersey **Location 14:** **City:** New York **Country:** United States **Facility:** New York Presbyterian - Columbia **State:** New York **Location 15:** **City:** Chapel Hill **Country:** United States **Facility:** Duke University **State:** North Carolina **Location 16:** **City:** Cincinnati **Country:** United States **Facility:** University of Cincinnati **State:** Ohio **Location 17:** **City:** Columbus **Country:** United States **Facility:** The Ohio State University **State:** Ohio **Location 18:** **City:** Oklahoma City **Country:** United States **Facility:** Oklahoma Cardiovascular Associates **State:** Oklahoma **Location 19:** **City:** Oklahoma City **Country:** United States **Facility:** University of Oklahoma **State:** Oklahoma **Location 20:** **City:** Philadelphia **Country:** United States **Facility:** Hospital of the University of Pennsylvania **State:** Pennsylvania **Location 21:** **City:** Philadelphia **Country:** United States **Facility:** Temple University Hospital **State:** Pennsylvania **Location 22:** **City:** Pittsburgh **Country:** United States **Facility:** University of Pittsburgh **State:** Pennsylvania **Location 23:** **City:** Charleston **Country:** United States **Facility:** Medical University of South Carolina **State:** South Carolina **Location 24:** **City:** Germantown **Country:** United States **Facility:** Baptist Memorial Hospital **State:** Tennessee **Location 25:** **City:** Nashville **Country:** United States **Facility:** St. Thomas Hospital **State:** Tennessee **Location 26:** **City:** Houston **Country:** United States **Facility:** St. Luke's Episcopal Hospital/Texas Heart **State:** Texas **Location 27:** **City:** Salt Lake City **Country:** United States **Facility:** LDS Hospital **State:** Utah **Location 28:** **City:** Seattle **Country:** United States **Facility:** University of Washington Medical Center **State:** Washington #### Overall Officials **Official 1:** **Affiliation:** The University of Alabama at Birmingham **Name:** Robert Bourge, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Zile MR, Adamson PB, Cho YK, Bennett TD, Bourge RC, Aaron MF, Aranda JM Jr, Abraham WT, Stevenson LW, Kueffer FJ. Hemodynamic factors associated with acute decompensated heart failure: part 1--insights into pathophysiology. J Card Fail. 2011 Apr;17(4):282-91. doi: 10.1016/j.cardfail.2011.01.010. Epub 2011 Feb 26. **PMID:** 21440865 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Treatment **Deaths Num Affected:** 13 **Deaths Num At Risk:** 134 **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** EG000 **Other Num Affected:** 15 **Other Num at Risk:** 134 **Serious Number Affected:** 79 **Serious Number At Risk:** 134 **Title:** Treatment **Group ID:** EG001 **Title:** Control **Deaths Num Affected:** 11 **Deaths Num At Risk:** 140 **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** EG001 **Other Num Affected:** 17 **Other Num at Risk:** 140 **Serious Number Affected:** 91 **Serious Number At Risk:** 140 **Title:** Control **Frequency Threshold:** 1 #### Other Events **Term:** Sustained VT **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Decompensated Heart Failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Angina **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Volume depletion/dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Volume overload **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** #### Serious Events **Term:** Decompensation of heart failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 35 **Num At Risk:** 134 **Num Events:** 57 **Group ID:** EG001 **Num Affected:** 43 **Num At Risk:** 140 **Num Events:** 68 **Term:** Volume overload **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 134 **Num Events:** 10 **Group ID:** EG001 **Num Affected:** 16 **Num At Risk:** 140 **Num Events:** 26 **Term:** Volume depletion/dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 134 **Num Events:** 6 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 140 **Num Events:** 6 **Term:** Angina pectoris **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 8 **Num At Risk:** 134 **Num Events:** 8 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Cardiovascular procedure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 134 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 140 **Num Events:** 6 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 140 **Num Events:** 4 **Term:** Non-specific chest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 134 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 140 **Num Events:** 4 **Term:** Non sustained VT **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 140 **Num Events:** 3 **Term:** Sustained VT **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 140 **Num Events:** 3 **Term:** Acute MI/Cardiac Arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 134 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 140 **Num Events:** 3 **Term:** Atrial tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Paroxysmal atrial flutter/fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 134 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Persistent atrial flutter/fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Ventricular fibrillation/flutter **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 134 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 140 **Num Events:** 2 **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 140 **Num Events:** 2 **Term:** Renal insufficiencies/failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 134 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Ascites **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Stroke **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Electro Mechanical Dis-association **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Hyponatremia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Hypokalemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 140 **Num Events:** 2 **Term:** Elective Surgery **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Inhalant Poisoning from Cleaning Agents **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications ##### Stats **Group ID:** EG000 **Num At Risk:** 134 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Sudden Cardiac Death **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 140 **Num Events:** 1 **Term:** Dyspnea/SOB **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 134 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Edema/weight gain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Lab value abnormalities **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 134 **Num Events:** 3 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Worsening COPD **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Pulmonary edema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Anemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Urinary Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Pleural effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Change in mental status **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Respiratory Failure/Arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** MRSA Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Cardiac Transplant **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Peripheral Vascular Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Allergic Reaction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Term:** Coronary Artery **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 134 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 140 **Time Frame:** 6 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 134 **Group ID:** BG001 **Value:** 140 **Group ID:** BG002 **Value:** 274 **Units:** Participants ### Group **ID:** BG000 **Title:** Treatment **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management ### Group **ID:** BG001 **Title:** Control **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 14 **Value:** 58 #### Measurement **Group ID:** BG001 **Spread:** 13 **Value:** 58 #### Measurement **Group ID:** BG002 **Spread:** 14 **Value:** 58 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 59 #### Measurement **Group ID:** BG001 **Value:** 50 #### Measurement **Group ID:** BG002 **Value:** 109 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 75 #### Measurement **Group ID:** BG001 **Value:** 90 #### Measurement **Group ID:** BG002 **Value:** 165 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 134 #### Measurement **Group ID:** BG001 **Value:** 140 #### Measurement **Group ID:** BG002 **Value:** 274 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Value:** 112 #### Measurement **Group ID:** BG001 **Value:** 122 #### Measurement **Group ID:** BG002 **Value:** 234 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 40 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** New York Heart Association Class III (NYHA III) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** New York Heart Association Class IV (NYHA IV) **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** dana.wigert@medtronic.com **Organization:** Medtronic **Phone:** 763-526-2802 **Title:** Dana Wigert ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 88.7 **CI Number of Sides:** ONE_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** Survival estimate at 6-months **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** 6-month survival rate **Parameter Value:** 91.5 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 98.9 **CI Number of Sides:** ONE_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** Survival estimate at 6-months **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** 6-month survival rate **Parameter Value:** 100 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 277 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 274 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.51 - **Spread:** - **Upper Limit:** 0.78 - **Value:** 0.63 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.67 - **Spread:** - **Upper Limit:** 0.97 - **Value:** 0.81 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 218 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 255 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 164.1 - **Spread:** - **Upper Limit:** 177.6 - **Value:** 170.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 166.6 - **Spread:** - **Upper Limit:** 178.9 - **Value:** 172.7 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48 **Title:** Improved ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 66 **Title:** Worsend ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 **Title:** Unchanged #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -69 - **Spread:** - **Upper Limit:** 42 - **Value:** -12.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -73 - **Spread:** - **Upper Limit:** 89 - **Value:** -8.5 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** NYHA I ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 **Title:** NYHA II ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70 **Title:** NYHA III ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** NYHA IV #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 98.8 - **Upper Limit:** - **Value:** 6.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 114.2 - **Upper Limit:** - **Value:** -8.2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** A Chronicle IHM system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death, (3) results in the explant of any Chronicle IHM component, and/or (4) causes permanent loss of significant function of the implanted system. Safety is defined as ≥ 80% of participants experiencing freedom from device related complications through 6 months. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The analysis population for safety includes all subjects with an attempted implant of the Chronicle implantable hemodynamic monitoring device, including both successful implanted participants (274) and unsuccessful implanted participants (3). In total 277 participants were assessed for the safety objective. **Reporting Status:** POSTED **Time Frame:** Within 6 months post-implant **Title:** Safety as Measured by the Percentage of Participants Free From System Related Complications Through 6 Months. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** All subjects with an attempted implant of a Chronicle IHM. **ID:** OG000 **Title:** All Subjects With Attempted Implant #### Outcome Measure 2 **Description:** A pressure sensor failure was defined as a recognizable, abrupt, non-physiologic shift in pressure parameters. Safety is defined as ≥ 90% of participants free from pressure sensor lead failure through 6 months. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Within 6 months post-implant **Title:** Safety as Measured by the Percentage of Participants Free From Implantable Hemodynamic Monitor Pressure Related Sensor Lead Failures Through 6 Months. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** All subjects successfully implanted with a Chronicle IHM system **ID:** OG000 **Title:** All Subjects Successfully Implanted #### Outcome Measure 3 **Description:** Hospital equivalents (HE) were defined to include the following events: 1. Heart failure-related hospital admissions for 24 hours or longer 2. Heart failure-related emergency department visits and necessitates invasive treatment (e.g. IV diuretic administration). 3. Heart failure-related urgent visits and necessitates invasive treatment (e.g. IV diuretic administration). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** All randomized subjects **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** Rate of Heart Failure-related Hospital Equivalents. **Type:** PRIMARY **Unit of Measure:** Events ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control #### Outcome Measure 4 **Description:** Characterize total health care utilization, the total number of all-cause hospitalization, emergency department, and urgent care visits. **Parameter Type:** NUMBER **Population Description:** All randomized subjects **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** Health Care Utilization **Type:** SECONDARY **Unit of Measure:** Total number of events ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control #### Outcome Measure 5 **Description:** The number of days alive outside the hospital was calculated as the number of days of randomized follow-up minus the number of days hospitalized during the randomized follow-up period. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** All randomized subjects **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** Days Hospitalization Free **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control #### Outcome Measure 6 **Description:** Worsened, Improved and Unchanged were defined as follows: Worsened: Patient died, hospitalized for worsening heart failure, worsened NYHA Class Improved: Patient improved in NYHA Class Unchanged: Patient was neither improved nor worsened. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** All randomized subjects **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** Clinical Composite Response of Either "Worsened", "Improved", or "Unchanged" **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control #### Outcome Measure 7 **Description:** Quality of life was measured by the Minnesota Living with Heart Failure (MLHF), a questionnaire with 21 questions and scored on a scale from 0 (good quality of life) to 105 (low quality of life). Change in quality of life is defined as change from baseline to month 6. A participant must have completed a quality of life survey at the baseline visit and month 6 visit to be included in the analysis. **Dispersion Type:** Full Range **Parameter Type:** MEAN **Population Description:** All randomized subjects completing a quality of life survey at the baseline visit and month 6 visit **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire **Type:** SECONDARY **Unit of Measure:** Index score ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control #### Outcome Measure 8 **Description:** New York Heart Association (NYHA) Classifications were defined as follows: Class I - Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or angina. Class II - Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or angina. Class III - Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or angina. Class IV - Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** All randomized subjects with NYHA assessment completed at baseline and at 6 months were included in the analysis **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** New York Heart Association (NYHA) Class **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control #### Outcome Measure 9 **Description:** Patients completed six minute hall walk at baseline and 6 months. Outcome is change in hall walk distance from baseline to 6 months. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All randomized patients completing a hall walk at baseline and 6 months. **Reporting Status:** POSTED **Time Frame:** 6 Months post-implant **Title:** Distance Walked During a Six Minute Hall Walk **Type:** SECONDARY **Unit of Measure:** Meters ##### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** OG000 **Title:** Treatment ##### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** OG001 **Title:** Control ### Participant Flow Module #### Group **Description:** Physicians have access to device-based hemodynamic monitor information to guide patient management **ID:** FG000 **Title:** Treatment #### Group **Description:** Physicians do not have access to device-based hemodynamic monitor information to guide patient management **ID:** FG001 **Title:** Control #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 13 ###### Reason **Group ID:** FG001 **Number of Subjects:** 11 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 134 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 140 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 118 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 127 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 16 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 13 **Pre-Assignment Details:** Subjects were required to have a successful implant of the Chronicle® device prior to randomization. 277 subjects had an attempted implant, with 274 successfully implanted and randomized. 3 subjects had unsuccessful implant attempts and were exited prior to randomization. **Recruitment Details:** Recruitment began on March 13, 2003 and ended on November 16, 2004. All subjects were exited from the study on April 8, 2013. Twenty-nine US clinical centers participated in the COMPASS-HF study. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00305279 **Brief Title:** The Effects of Dietary Phosphate Intake on Calciotropic Hormones and FGF23. **Official Title:** The Effects of Dietary Phosphate Intake on Calciotropic Hormones and FGF23 #### Organization Study ID Info **ID:** H40550-27771 #### Organization **Class:** OTHER **Full Name:** University of California, San Francisco #### Secondary ID Infos **ID:** 1K23RR020343 **Link:** https://reporter.nih.gov/quickSearch/1K23RR020343 **Type:** NIH ### Status Module #### Completion Date **Date:** 2009-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2013-10-10 **Type:** ESTIMATED **Last Update Submit Date:** 2013-10-09 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2009-12 **Type:** ESTIMATED #### Start Date **Date:** 2006-02 **Status Verified Date:** 2013-10 #### Study First Post Date **Date:** 2006-03-21 **Type:** ESTIMATED **Study First Submit Date:** 2006-03-17 **Study First Submit QC Date:** 2006-03-17 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institutes of Health (NIH) #### Lead Sponsor **Class:** OTHER **Name:** University of California, San Francisco #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** The purpose of this study is to determine the effects of different amounts of phosphorus in the diet on hormones that control phosphorus and bone health both in people who are healthy and in ones who have moderate kidney disease. **Detailed Description:** Chronic kidney disease affects 11% of the US population; over half of those affected have skeletal manifestations of their renal disease. Renal osteodystrophy is a complex disease, in which multiple mineral systems and related hormones play a role, including phosphate homeostasis. Phosphate regulation primarily depends on renal handling of phosphate, which is partly controlled by parathyroid hormone and vitamin D. However, other mediators in this system clearly exist. Recently, evidence has been accruing that one such factor may be FGF23, a protein produced by osteogenic cells. States of excess FGF23 are associated with marked phosphate wasting, hypophosphatemia, osteomalacia, and inappropriately low calcitriol. FGF23 levels are measurable in healthy humans and markedly elevated in patients who require hemodialysis, although its physiologic role in either state is unknown. Some retrospective evidence suggests that FGF23 is affected by phosphate intake. We are performing a study to gather data describing the response of FGF23 to changes in dietary phosphorus intake in healthy men and women and in men and women with moderate renal insufficiency. The specific aims of this pilot study are: 1) To examine the physiologic effects of alterations in dietary phosphorus on FGF23 in healthy subjects; 2) To examine the physiologic response of FGF23 to dietary phosphorus alterations in patients with moderate renal failure; and 3) To assess whether serum levels of 1,25-dihydroxyvitamin D vary inversely with those of FGF23 when dietary phosphate is changed. The proposed research plan is a dietary intervention trial in which we will study the response of serum FGF23 levels to diets with varying phosphorus contents in healthy adults and adults with moderate renal insufficiency. ### Conditions Module **Conditions:** - Healthy - Kidney Failure, Chronic ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT #### Enrollment Info **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Other: Dietary **Label:** 1 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Other: Dietary **Label:** 2 **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Intervention Names:** - Other: Dietary **Label:** 3 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** Dietary **Name:** Dietary **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - 2 **Description:** Dietary **Name:** Dietary **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - 3 **Description:** Dietary **Name:** Dietary **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Hormonal regulators of mineral metabolism **Time Frame:** Last two days of each intervention phase ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: HEALTHY SUBJECTS: * Men 21-65 years of age; * Premenopausal women over 21 years of age taking oral contraceptives; * Postmenopausal women less than 65 years of age; CHRONIC KIDNEY DISEASE SUBJECTS: * Men 21-65 years of age; * Premenopausal women over 21 years of age taking oral contraceptives; * Postmenopausal women less than 65 years of age; * Creatinine clearance between 30 and 59 ml/min/1.73 m2 as calculated using the equation derived from the Modification of Diet in Renal Disease (MDRD) study. Exclusion Criteria: * Medications affecting bone metabolism; * Abnormal liver or GI function; * Extreme electrolyte abnormalities; * BMI \>30 kg/m2. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Francisco **Country:** United States **Facility:** University of California **State:** California **Zip:** 94143 #### Overall Officials **Official 1:** **Affiliation:** University of California, San Francisco **Name:** Diana M Antoniucci, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10699 - Name: Kidney Failure, Chronic - Relevance: HIGH - As Found: Kidney Failure, Chronic - ID: M26718 - Name: Renal Insufficiency - Relevance: HIGH - As Found: Kidney Failure - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M26717 - Name: Renal Insufficiency, Chronic - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000051437 - Term: Renal Insufficiency - ID: D000007676 - Term: Kidney Failure, Chronic ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04739579 **Brief Title:** Post-operative CRP Trend After Ileocolic Resection in Crohn's Disease Patients. **Official Title:** Post-operative CRP Trend May Lead to Early Diagnosis of Anastomotic Leak After Ileocolic Resection in Crohn's Disease Patients. #### Organization Study ID Info **ID:** 2020PI287 #### Organization **Class:** OTHER **Full Name:** Central Hospital, Nancy, France ### Status Module #### Completion Date **Date:** 2021-03-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-07-01 **Type:** ACTUAL **Last Update Submit Date:** 2021-06-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-02-01 **Type:** ACTUAL #### Start Date **Date:** 2021-01-27 **Type:** ACTUAL **Status Verified Date:** 2021-06 #### Study First Post Date **Date:** 2021-02-04 **Type:** ACTUAL **Study First Submit Date:** 2021-01-28 **Study First Submit QC Date:** 2021-02-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Central Hospital, Nancy, France #### Responsible Party **Investigator Affiliation:** Central Hospital, Nancy, France **Investigator Full Name:** ADELINE GERMAIN **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Our aim is to analyze C-Reactive Protein trends during the post-operative course in Crohn's Disease patients having undergone ileocolic resection and primary anastomosis, for the purpose of anastomotic leak early diagnosis. ### Conditions Module **Conditions:** - Crohn Disease **Keywords:** - Crohn Disease - Anastomotic Leak - C-Reactive Protein ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 59 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Diagnostic Test: C-Reactive Protein **Label:** Anastomotic Leak #### Arm Group 2 **Intervention Names:** - Diagnostic Test: C-Reactive Protein **Label:** Non-Anatomotic Leak ### Interventions #### Intervention 1 **Arm Group Labels:** - Anastomotic Leak - Non-Anatomotic Leak **Description:** C-Reactive Protein trend in post-operative course **Name:** C-Reactive Protein **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Presence of a collection in the area of the anastomosis on computed tomography scan or evident anastomotic dehiscence at reoperation for peritonitis. **Measure:** Anastomotic leak **Time Frame:** up to 30 days following surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Crohn's disease patients * Primary ileocolic anastomosis * C-Reactive Protein data available in medical file Exclusion Criteria: * Protective stoma * Associated resection with or without anastomosis during intervention **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients undergoing ileocolic resection with primary anastomosis ### Contacts Locations Module #### Locations **Location 1:** **City:** Nancy **Country:** France **Facility:** CHRU de Nancy #### Overall Officials **Official 1:** **Affiliation:** Central Hospital, Nancy, France **Name:** Adeline Germain, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000015212 - Term: Inflammatory Bowel Diseases - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6638 - Name: Crohn Disease - Relevance: HIGH - As Found: Crohn's Disease - ID: M28891 - Name: Anastomotic Leak - Relevance: HIGH - As Found: Anastomotic Leak - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M17917 - Name: Inflammatory Bowel Diseases - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003424 - Term: Crohn Disease - ID: D000057868 - Term: Anastomotic Leak ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02240979 **Brief Title:** Establishing a Non-invasive Method to Measure Your Heart's Performance **Official Title:** Establishing a Non-invasive Method to Measure Heart Performance #### Organization Study ID Info **ID:** HMRI-10Pico-1 #### Organization **Class:** OTHER **Full Name:** Huntington Medical Research Institutes #### Secondary ID Infos **Domain:** California Institute of Technology Boswell Fellowship **ID:** CIT2014 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2019-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-05-14 **Type:** ACTUAL **Last Update Submit Date:** 2019-05-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-05 **Type:** ACTUAL #### Start Date **Date:** 2014-08 **Type:** ACTUAL **Status Verified Date:** 2019-05 #### Study First Post Date **Date:** 2014-09-16 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-12 **Study First Submit QC Date:** 2014-09-15 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Southern California **Class:** OTHER **Name:** California Institute of Technology #### Lead Sponsor **Class:** OTHER **Name:** Marie Csete MD, PhD #### Responsible Party **Investigator Affiliation:** Huntington Medical Research Institutes **Investigator Full Name:** Marie Csete MD, PhD **Investigator Title:** Chief Scientific Officer **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of the study is to evaluate a new way to examine cardiac function, using software developed at Caltech. The experimental device is software loaded on an iPhone. The iPhone is used to capture a pulse (waveform) by simply placing the iPhone lightly over the neck where the carotid pulse can be felt. In this study the information collected from the iPhone app is compared to cardiac function data obtained from the current gold standard for measuring cardiac function, cardiac magnetic resonance imaging (MRI). Subjects referred from cardiologists will also generally have echocardiography information available for comparison with the iPhone app. For the study, subjects will have completely non-invasive studies done in one setting: The iPhone app to capture the waveforms (over carotid and radial (wrist) arteries), tonometry (another non-invasive method using a modified stethoscope), standard pulse oximetry, followed by a 30 minute MRI examination of the heart. A second complete study will be done about 6 months after the first. The complete study session takes about 1.5 hours. **Detailed Description:** Investigators at Caltech have developed an iPhone-based application that allows them to capture an arterial waveform using the iPhone camera held over the skin. Then based on the captured waveform and previous laboratory experiments and models, the investigators are able to calculate ejection fraction, the percentage of blood that goes out of the heart into the circulation with each beat. Previous studies suggested that the iPhone app measurements of ejection fraction were similar to those obtained with traditional cardiac echocardiography. In the current study the iPhone app measures are being compared to ejection fraction obtained using cardiac MRI. The iPhone also measures other physical properties of the heart and aorta that the investigators call "intrinsic frequencies". Using healthy subjects they have established the normal pattern/range of intrinsic frequencies, and in this study, a more diverse population of subjects (some with heart disease) will be studied, to determine how intrinsic frequency measures compare to traditional clinical measures of cardiac function. ### Conditions Module **Conditions:** - Heart Failure **Keywords:** - arterial waveform - cardiac magnetic resonance imaging - echocardiography - intrinsic frequency measures of cardiac function ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 72 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Adults able to undergo cardiac MRI **Intervention Names:** - Device: cardiac MRI **Label:** Adults able to undergo cardiac MRI exam ### Interventions #### Intervention 1 **Arm Group Labels:** - Adults able to undergo cardiac MRI exam **Description:** cardiac MRI **Name:** cardiac MRI **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Standard end-points of cardiac function such as chamber size and relaxation. **Measure:** Magnetic resonance measures of cardiac function **Time Frame:** Within 1 month of study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult age 18-90, outpatients Exclusion Criteria: * Inability to lie flat for 30 minutes with periodic breath holding * Metal implants or other standard contraindications to MRI * Acute cardiac decompensation (active chest pain, shortness of breath) * Hypotension (SBP\<90 mm Hg) * Claustrophobia * Patient too large to fit in closed MRI **Healthy Volunteers:** True **Maximum Age:** 90 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adults with normal and abnormal cardiac function will be studied. ### Contacts Locations Module #### Locations **Location 1:** **City:** Pasadena **Country:** United States **Facility:** Avicena LLC **State:** California **Zip:** 91105 **Location 2:** **City:** Pasadena **Country:** United States **Facility:** Huntington Medical Research Institutes MR Imaging Center **State:** California **Zip:** 91105 #### Overall Officials **Official 1:** **Affiliation:** Avicena LLC **Name:** Marie Csete, MD, PhD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** University of Southern California **Name:** Niema Pahlevan, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** A manuscript was submitted in February 2016 reporting results of the study. In editorial process. **IPD Sharing:** YES ### References Module #### References **Citation:** Pahlevan NM, Tavallali P, Rinderknecht DG, Petrasek D, Matthews RV, Hou TY, Gharib M. Intrinsic frequency for a systems approach to haemodynamic waveform analysis with clinical applications. J R Soc Interface. 2014 Sep 6;11(98):20140617. doi: 10.1098/rsif.2014.0617. **PMID:** 25008087 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03144479 **Brief Title:** New Technique to Assess Correct Positioning of the Right-sided Double Lumen Tube **Official Title:** A New Technique to Assess the Correct Positioning of a Right-sided Double-lumen Tube Without Fiberoptic Bronchoscopy #### Organization Study ID Info **ID:** 2016/29dec/565 #### Organization **Class:** OTHER **Full Name:** Cliniques universitaires Saint-Luc- Université Catholique de Louvain ### Status Module #### Completion Date **Date:** 2017-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-09-11 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-12-31 **Type:** ACTUAL #### Start Date **Date:** 2017-03-10 **Type:** ACTUAL **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2017-05-08 **Type:** ACTUAL **Study First Submit Date:** 2017-03-29 **Study First Submit QC Date:** 2017-05-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cliniques universitaires Saint-Luc- Université Catholique de Louvain #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A technique not yet described in the literature and allowing anesthesiologists who do not regularly practice fibroscopy or who do not routinely have this type of apparatus for their procedures, to install straight double-lumen tubes without compromising the ventilation of the patient. The aim is to introduce a central venous catheter wire guide into the bronchial arm of the right double-lumen tube and insert it into the right upper lobe bronchus orifice under fluoroscopic control. Then, to validate the new technique, we will carry out a fibroscopic control. **Detailed Description:** Right-sided double lumen tube (Mallinckrodt - Endobronchial tube) is introduced into the glottis via direct laryngoscopy. After the endotracheal lumen tube has passed the vocal cords, the stylet is removed, and the tube is rotated 90° toward the right and advanced slightly until resistance is encountered. Auscultation is then performed to check the proper side the endobronchial tube was inserted to. Then, the anatomy of the carina and the origins of the right and left upper bronchus are identified with the video-bronchoscopy. After a mild plication of the distal extremity of an adult central venous catheter wire guide (0.53mm diameter, 45cm length, one straight soft tip on one end and one "J" tip on other), the J-shaped extremity of this guide is introduced through the endobronchial lumen under direct video-bronchoscope. The wire guide is then slowly removed in order that proper alignment between the wire extremity and the right upper lobe occurs. The wire is removed again until its J-shaped extremity appears through the right-upper lobe ventilation orifice. In order to align the orifice of the tube with the upper lobe bronchus, a rotational movement of the double-lumen tube may be necessary. When the location of the orifice of the right upper lobe is identified, the guide is moved forward through the orifice into the upper lobe bronchus. Once satisfactory initial placement is achieved, the bronchial cuff is left inflated, the wire guide of the central venous catheter is kept in place in the upper lobe bronchus, and the patient is turned to the right lateral decubitus position. The proper positioning of the tube is once again checked by another video-bronchoscopy. To confirm the exact placement of the tube, a fiberoptic bronchoscopy is performed through the endobronchial lumen to find the right upper lobe ventilation orifice and confirm alignment. Then, it is placed distally to the endobronchial lumen to confirm a clear view showing the bronchus intermedius. After passing the fiberoptic bronchoscope through the tracheal lumen, the blue bronchial cuff is visualized at the origin of the right main stem bronchus below the level of the carina. ### Conditions Module **Conditions:** - Anesthesia - Thoracic Diseases ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** DEVICE_FEASIBILITY #### Enrollment Info **Count:** 10 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** positioning of the right-sided double lumen tube with a wire guide and fluoroscopy **Intervention Names:** - Procedure: right-sided double lumen tube **Label:** Positioning of right-sided double lumen tube with fluoroscopy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** positioning of the right sided double lumen tube in the same patient but with a fibroscope **Intervention Names:** - Procedure: right-sided double lumen tube **Label:** Positioning of right-sided double lumen tube with fibroscope **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Positioning of right-sided double lumen tube with fibroscope - Positioning of right-sided double lumen tube with fluoroscopy **Description:** Verification of a new technique to assess the correct positioning of a right-sided double-lumen tube for left thoracic surgeries, using a central venous catheter wire guide and a radioscopy **Name:** right-sided double lumen tube **Other Names:** - Device intervention : central venous catheter wire guide and radioscopy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Fibroscopic measurement to assess the correct positioning of the right-sided double lumen tube with the wire guide and the fluoroscopy **Measure:** Measurement of the distance between the lateral orifice of the tube and the orifice of the right upper lobe bronchus **Time Frame:** 20 minutes #### Secondary Outcomes **Description:** If the technique with the wire guide and the fluoroscopy, takes more than 20 minutes to be achieved, it is considered as failed. **Measure:** Total time spent to correctly position the right-sided double lumen tube **Time Frame:** 20 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * all patients \> 18 years old who have to undergo a left thoracic surgery with a one lung ventilation technique Exclusion Criteria: * emergency surgical procedures, patients with predictable difficulties of insertion of a double-lumen endotracheal tube, hemodynamically unstable patients **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Brussels **Country:** Belgium **Facility:** Cliniques universitaires Saint-Luc **Zip:** 1200 #### Overall Officials **Official 1:** **Affiliation:** Cliniques universitaires Saint-Luc **Name:** Christine Watremez, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Campos JH, Massa FC, Kernstine KH. The incidence of right upper-lobe collapse when comparing a right-sided double-lumen tube versus a modified left double-lumen tube for left-sided thoracic surgery. Anesth Analg. 2000 Mar;90(3):535-40. doi: 10.1097/00000539-200003000-00007. **PMID:** 10702432 **Citation:** de Bellis M, Accardo R, Di Maio M, La Manna C, Rossi GB, Pace MC, Romano V, Rocco G. Is flexible bronchoscopy necessary to confirm the position of double-lumen tubes before thoracic surgery? Eur J Cardiothorac Surg. 2011 Oct;40(4):912-6. doi: 10.1016/j.ejcts.2011.01.070. Epub 2011 Jul 29. Erratum In: Eur J Cardiothorac Surg. 2012 Jun;41(6):1411. Lamanna, Carmine [corrected to La Manna, Carmine]. **PMID:** 21802958 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M16655 - Name: Thoracic Diseases - Relevance: HIGH - As Found: Thoracic Diseases - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013896 - Term: Thoracic Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05700279 **Brief Title:** Preventing the Development of Chronic Pain: Treating PTSD at Acute Pain Onset **Official Title:** Preventing the Development of Chronic Pain: Treating PTSD at Acute Pain Onset #### Organization Study ID Info **ID:** 21092002 #### Organization **Class:** OTHER **Full Name:** Rush University Medical Center ### Status Module #### Completion Date **Date:** 2027-02-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-10 **Type:** ACTUAL **Last Update Submit Date:** 2023-10-06 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-02-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-09-01 **Type:** ACTUAL **Status Verified Date:** 2023-10 #### Study First Post Date **Date:** 2023-01-26 **Type:** ACTUAL **Study First Submit Date:** 2023-01-17 **Study First Submit QC Date:** 2023-01-17 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** United States Department of Defense #### Lead Sponsor **Class:** OTHER **Name:** Rush University Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Although most people recover from acute pain (such as pain caused by injury, surgery, repetitive motion, or unknown causes), many people do not fully recover and will experience chronic pain. Untreated posttraumatic stress disorder (PTSD) appears to be a key risk factor for the transition from acute pain to chronic pain. However, few published studies have addressed the issue of preventing the transition from acute to chronic pain via PTSD reduction. This project will aim to test whether trauma-related PTSD symptoms can be reduced using either Stellate Ganglion Block (SGB) treatment or Cognitive Processing Therapy (CPT), and whether reducing PTSD symptoms can prevent the transition from non-injury based acute pain to chronic pain. **Detailed Description:** Untreated PTSD appears to be a key risk factor for the transition from acute pain to chronic pain. Thus, reducing PTSD symptoms during an acute pain episode may potentially decrease the likelihood of transitioning to chronic pain. CPT is an evidence-based trauma-focused cognitive behavioral treatment that is hypothesized to reduce PTSD symptoms via reducing negative trauma-related cognitions about oneself, others, and the world. SGB treatment is an injection of a local anesthetic into the stellate ganglion, which is a bundle of nerves located at the base of the neck that is part of the sympathetic nervous system. Previous studies suggest that 1-week massed CPT and SGB treatment can both reduce the severity of PTSD symptoms in short periods of time via two distinct psychological and biological mechanisms. This 4 year project will test study hypotheses in a sample of 345 individuals with PTSD symptoms who present to the Emergency Department (ED) with non-injury based acute pain. Participants will be randomly assigned to receive 1-week massed CPT, 2 SGB treatments, or usual care. All participants will complete identical self-report and/or clinician administered assessments at baseline (prior to randomization) and on study days 1, 7, 14, 21, 28, 56 (approximately 3 months after the initial ED presentation), and 112 (approximately 6 months after ED presentation). ### Conditions Module **Conditions:** - PTSD - Chronic Pain **Keywords:** - PTSD - Chronic Pain - Acute Pain ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 345 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants randomly assigned to the Stellate Ganglion Block (SGB) condition will receive 2 SGB treatments separated by 2 weeks. **Intervention Names:** - Procedure: Stellate Ganglion Block **Label:** Stellate Ganglion Block Treatment **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Participants randomly assigned to the Cognitive Processing Therapy (CPT) condition will receive 1-week massed CPT treatment consisting of 10 CPT sessions given within a single 5-day period via telehealth. **Intervention Names:** - Behavioral: Cognitive Processing Therapy **Label:** Cognitive Processing Therapy **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Participants randomly assigned to the Usual Care condition will not receive any active intervention. **Label:** Usual Care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Stellate Ganglion Block Treatment **Description:** Stellate Ganglion Block (SGB) procedure involves an injection of a local anesthetic (0.5% ropivacaine) around the stellate ganglion (a bundle of nerves located at the base of the neck) to block the transmission of pain signals. The SGB injection is administered by an anesthesiologist. **Name:** Stellate Ganglion Block **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Cognitive Processing Therapy **Description:** Cognitive Processing Therapy (CPT) is a form of trauma-based talk therapy that will be conducted by clinical therapists. CPT can help people identify and challenge unhelpful trauma-related beliefs about themselves, others, and the world. **Name:** Cognitive Processing Therapy **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Intensity of chronic pain reported by subject. The PROMIS Pain Intensity scale consists of 3 questions with a 5-point response scale ranging from "Had no pain" -to "Very severe. " Participants are asked how intense their pain has been in the past 7 days. Higher scores indicate more intense pain. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity **Time Frame:** Through study completion, for an average of 6 months **Description:** PCL-5 will be used to measure self-reported PTSD symptoms. The PCL-5 consists of 20 questions that ask how much a given symptom has bothered the participant within a specified time period. Each question has a 5 point response scale ranging from "not at all" (0) to "extremely" (4). Higher scores indicate greater PTSD symptom severity. **Measure:** Change in PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (PCL-5) Self-Reported PTSD Symptoms **Time Frame:** Through study completion, for an average of 6 months **Description:** Clinician Administered PTSD Scale for DSM-5 (CAPS-5) will be administered by a trained interviewer for formal assessment for PTSD diagnosis. The CAPS-5 is a semi-structured interview measure consisting of 30 items. Interviewers assess the frequency and intensity of PTSD symptoms; These frequency and severity scores for each item are then combined into one symptom severity score for each item that ranges from "absent" (0) to "extreme/incapacitating" (4). Higher scores indicate greater PTSD symptom severity. **Measure:** Change in CAPS-5 PTSD Diagnosis **Time Frame:** Through study completion, for an average of 6 months #### Secondary Outcomes **Description:** The Structured Clinical Interview for the DSM-5 (SCID-5) is a semi-structured interview measure for making DSM-5 diagnoses. The SCID-5 will be administered by a trained interviewer for assessment of mood and anxiety disorders. **Measure:** Change in SCID-5 mood and anxiety disorder diagnoses **Time Frame:** Through study completion, for an average of 6 months **Description:** The Alcohol Use Disorder Identification Test (AUDIT-C) is a self-report questionnaire consisting of 12 items that ask participants about the frequency of their alcohol and substance use both generally and within the past 2 weeks (14 calendar days). **Measure:** Change in AUDIT-C Self-Reported Substance Use **Time Frame:** Through study completion, for an average of 6 months **Description:** Interference in daily activities attributed to chronic pain as reported by subjects. The PROMIS Pain Interference scale consists of 8 questions with a 5-point response scale ranging from "Not at all" to "Very much." Participants are asked how much in the past 7 days everyday activities were affected by their pain. Higher scores indicate more pain interference in daily activities. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference **Time Frame:** Through study completion, for an average of 6 months **Description:** Degree of depressive symptoms reported by subject. The PROMIS Depression scale consists of 8 questions with a 5-point response scale ranging from "Never" to "Always." Participants are asked how often they felt depressive emotions in the past 7 days. Higher scores indicate more depressive emotions. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression (Short Form) **Time Frame:** Through study completion, for an average of 6 months **Description:** Amount of physical activity reported by subject. The PROMIS Physical Function scale consists of 10 questions with a 5-point response scale ranging from "Without any difficulty" to "Unable to do." Participants are asked how much their pain affects their physical functioning. Higher scores indicate more inability to perform specific physical activities due to pain. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (Short Form) **Time Frame:** Through study completion, for an average of 6 months **Description:** Degree of sleep disturbance reported by subject. The PROMIS Sleep Disturbance scale consists of 8 questions with a 5-point response scale ranging from "Not at all" to "Very much." Participants are asked how much in the past 7 days their symptoms interfered with their sleep. Higher scores indicate more sleep disruptions. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance (short form) **Time Frame:** Through study completion, for an average of 6 months **Description:** Degree of anxiety symptoms reported by subject. The PROMIS Anxiety scale consists of 7 questions with a 5-point response scale ranging from "Never" to "Always." Participants are asked how often they experienced anxiety symptoms in the past 7 days. Higher scores indicate more anxiety symptoms. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety (short form) **Time Frame:** Through study completion, for an average of 6 months **Description:** Degree of anger reported by subject. The PROMIS Anger scale consists of 5 questions with a 5-point response scale ranging from "Never" to "Always." Participants are asked how often they experienced anger in the past 7 days. Higher scores indicate more frequent anger. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) anger (short form) **Time Frame:** Through study completion, for an average of 6 months **Description:** Satisfaction with social roles reported by subject. The PROMIS Satisfaction with Social Roles scale consists of 7 questions with a 5-point response scale ranging from "Not at all" to "Very Much." Participants are asked how satisfied they have felt with their performance in various social roles in the past 7 days. Higher scores indicate greater satisfaction. **Measure:** Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Satisfaction with Social Roles **Time Frame:** Through study completion, for an average of 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age 18 to 70 years 2. Ability to read and write English sufficiently to understand and complete study questionnaires and participate in interviews 3. Presenting to the Rush Emergency Department (ED) with a medical problem and experiencing non-injury based acute pain 4. A primary acute pain site of chest, back, shoulder, abdomen, or pelvis 5. Self-reported symptoms consistent with a diagnosis of PTSD Exclusion Criteria: 1. Pain intensity great enough to impair concentration or capacity to understand instructions or nature of being invited into a study, as assessed by a member of medical staff 2. Any illness or injury that precludes the ability to understand or follow instructions, as assessed by a member of the medical staff 3. Current illness that involves constant or frequent pain 4. Self-reported history of chronic pain on presentation to the ED or documented in the electronic medical record 5. Pain from the traumatic event that is the source of their PTSD 6. Neurological disorder 7. Cancer diagnosis 8. Blood pressure greater than 160/100 mmHg 9. Taking anticoagulants or antiplatelet drugs other than aspirin 10. Pregnancy 11. Current or lifetime psychotic or bipolar disorders 12. Current alcohol or substance dependence 13. Receiving treatment for chronic or significant disease such rheumatoid disease, current influenza that may manifest temporary flu-related pain, and heart disease. People with well-controlled diabetes or HIV/AIDS will be included only if there is no self-reported history of chronic or neuropathic pain on presentation to the ED or documented in the electronic medical record. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** john_burns@rush.edu **Name:** John W Burns, PhD **Phone:** 312-942-0379 **Role:** CONTACT #### Locations **Location 1:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Email:** john_burns@rush.edu - **Name:** John W Burns, PhD - **Phone:** 312-942-0379 - **Role:** CONTACT **Country:** United States **Facility:** Rush University Medical Center **State:** Illinois **Status:** RECRUITING **Zip:** 60612 #### Overall Officials **Official 1:** **Affiliation:** Rush University Medical Center **Name:** John W Burns, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2023-04-25 - Filename: ICF_000.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 341129 - Type Abbrev: ICF - Upload Date: 2023-06-19T16:55 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M29442 - Name: Chronic Pain - Relevance: HIGH - As Found: Chronic Pain - ID: M29525 - Name: Acute Pain - Relevance: HIGH - As Found: Acute Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000059350 - Term: Chronic Pain - ID: D000059787 - Term: Acute Pain ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1700 - Name: Ropivacaine - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05684679 **Brief Title:** Effectiveness of Incentive Spirometer and Diaphragmatic Breathing Exercise on ABG Measures in Post-CABG Patients **Official Title:** Efficacy of Incentive Spirometer and Diaphragmatic Breathing Exercise on the Alteration of Arterial Blood Gas Measures in Patients After Coronary Artery Bypass Grafting. A Randomized Comparative Study #### Organization Study ID Info **ID:** RRC-2019-13 #### Organization **Class:** OTHER **Full Name:** King Saud University ### Status Module #### Completion Date **Date:** 2019-08-25 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-01-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-07-30 **Type:** ACTUAL #### Start Date **Date:** 2019-04-15 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2023-01-13 **Type:** ACTUAL **Study First Submit Date:** 2023-01-04 **Study First Submit QC Date:** 2023-01-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** King Saud University #### Responsible Party **Investigator Affiliation:** King Saud University **Investigator Full Name:** AMIR IQBAL **Investigator Title:** Prinicipal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The rate of pulmonary complications following Coronary artery bypass graft (CABG) is high. Early pulmonary exercises are important in preventing this complication following cardiac surgery. This study aimed to investigate the effectiveness of incentive spirometer (IS) and diaphragmatic breathing exercise (DBE) on the alteration of arterial blood gas (ABG) measures. The study was based on a two-arm, parallel-group, randomized comparative design. Thirty patients who underwent CABG enrolled in the study based on inclusion and exclusion criteria, randomly allocated into either of the groups, IS Group or DBE Group. IS Group and DBE Group underwent chest physiotherapy with IS and DBE, respectively. ABG measures, including PH of blood, partial pressure of arterial oxygen molecule (PaO2), and partial pressure of arterial carbon dioxide (PaCO2), was assessed using an ABG analyzer at baseline (pre-operation), day1 post-operation, and day2 post-operation. The significance level was kept constant for all statistical analyses at 95%. **Detailed Description:** Coronary artery bypass graft (CABG) is one of common treatment procedures performed worldwide. Evidence suggest that every year more than 1 million CABG procedure has been performed. Pulmonary complications are one of the most common consequence post CABG. The incidence of atelectasis after heart operation with cardiopulmonary bypass is still 80-84% in spite of careful fluid \& respiratory management. The basic problem in respiratory care of post-surgical patient is atelectasis leading to hypoxemia causing alteration in arterial blood gases (ABGs). Associated with atelectasis are widening alveolar - arterial O2 gradient (as right to left intrapulmonary shunting increases) decrease ventilation perfusion ratio, decrease functional residual capacity and decrease compliance. Chest physiotherapy is routinely used after major abdominal \& cardiothoracic surgery to prevent these pulmonary complications following operation. To date, there is a variable view about the effectiveness of these two primary breathing exercise techniques (incentive spirometer and diaphragmatic breathing exercise). 10-12 Hence an effort to systematically study the effectiveness of these is attempted. Thus, the current study aimed to determine the efficacy of incentive spirometer and diaphragmatic breathing exercises in addition to conventional chest physiotherapy on alteration of ABG measures in patients with post CABG. This study hypothesized that there will be a significant difference between the effect of the IS and DBE on ABG alteration in post CABG patients. ### Conditions Module **Conditions:** - Post Coronary Artery Bypass Grafting **Keywords:** - Chest Physiotherapy - Incentive spirometer - Diaphragmatic breathing ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** • Patients were instructed to utilize an incentive spirometer in the sitting or half lying position as taught preoperatively. * 3 to 5 consecutive breath with the spirometer were interspersed between period of quite breathing. * Duration 10-15 minutes/session. **Intervention Names:** - Other: Incentive spirometer plus Chest physiotherapy **Label:** IS Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** • Patients were advised to do diaphragmatic breathing exercise in the sitting or half lying position as taught preoperatively. * 3 to 5 consecutive deep breath were interspersed between period of quite breathing. * Duration 10-15 minutes/session. **Intervention Names:** - Other: Diaphragmatic breathing exercise plus Chest physiotherapy **Label:** DBE Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - IS Group **Description:** Incentive spirometer was given to IS group. However, a conventional chest physiotherapy was given to both groups in the optimal position. **Name:** Incentive spirometer plus Chest physiotherapy **Other Names:** - Huffing, Coughing, Upper and lower limbs active exercises **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - DBE Group **Description:** Diaphragmatic breathing exercise was given to DBE group. In addition, a conventional chest physiotherapy was given in the optimal position. **Name:** Diaphragmatic breathing exercise plus Chest physiotherapy **Other Names:** - Huffing, Coughing, Upper and lower limbs active exercises **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** PH of blood was assessed using an ABG analyzer machine **Measure:** PH of Blood **Time Frame:** 3 Days **Description:** PaO2 was assessed using an ABG analyzer machine **Measure:** Partial pressure of Arterial Oxygen molecule (PaO2) **Time Frame:** 3 Days **Description:** PaCO2 was assessed using an ABG analyzer machine **Measure:** Partial pressure of Arterial Carbon dioxide molecule (PaCO2) **Time Frame:** 3 Days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * The patient with post-CABG, * Aged between 40 and 60 years, * Had forced expiratory volume in 1 second (FEV1) \<70% of predicted value, * Showed FEV1/forced vital capacity (FVC) ratio \>0.8, * Weight equal or exceeded the ideal body weight by less than 20%, and * Patient co-operation. Exclusion Criteria: * Aged more than 60 years, * Weight equal or exceeded the ideal body weight by more than 20%, * Post-operative respiratory treatment exceeding 20 hours, * History of Chronic obstructive pulmonary disease (COPD) /thoracic surgery including CABG, * had thoracic anomalies/unstable angina, * Developed hemodynamic complication, and * Non-cooperative/neurological debilitated patient. **Maximum Age:** 60 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Riyadh **Country:** Saudi Arabia **Facility:** Rehabilitation Research Chair, Department of Rehabilitation Sciences, king Saud University **State:** Riyadh 11433 **Zip:** 10219 #### Overall Officials **Official 1:** **Affiliation:** King Saud University, Riyadh, Saudi Arabia **Name:** AMIR IQBAL, MPT **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012120 - Term: Respiration Disorders - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M27137 - Name: Respiratory Aspiration - Relevance: HIGH - As Found: Breathing - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000053120 - Term: Respiratory Aspiration ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04086979 **Brief Title:** Parents as Friendship Coaches for Children With ADHD **Official Title:** Parents as Friendship Coaches for Children With Attention-Deficit/Hyperactivity Disorder #### Organization Study ID Info **ID:** 285413 #### Organization **Class:** OTHER **Full Name:** University of British Columbia ### Status Module #### Completion Date **Date:** 2018-07-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-12 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-07-01 **Type:** ACTUAL #### Start Date **Date:** 2013-09-01 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2019-09-12 **Type:** ACTUAL **Study First Submit Date:** 2019-09-06 **Study First Submit QC Date:** 2019-09-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of British Columbia #### Responsible Party **Investigator Affiliation:** University of British Columbia **Investigator Full Name:** Amori Yee Mikami **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Many children with Attention-Deficit/Hyperactivity Disorder (ADHD) have problems with making and keeping friends. The current study compared the efficacy of two 10-week behavioral interventions for improving the friendships of children with this disorder. Participants were children ages 6-11 with ADHD and their families, who were experiencing friendship problems. Outcome measures assessed friendship quality and friendship behaviors at baseline (pre-treatment), post-treatment, and 8-month follow-up. ### Conditions Module **Conditions:** - ADHD **Keywords:** - friendship ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants were randomly assigned to one of two interventions: Parental Friendship Coaching (PFC) or Coping with ADHD through Relationships and Education (CARE) ##### Masking Info **Masking:** SINGLE **Masking Description:** Some outcomes were observed by coders unaware of the participant's intervention condition. Other outcomes were reported by participants who were aware of their intervention condition. **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 172 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: Parental Friendship Coaching **Label:** Parental Friendship Coaching (PFC) **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Behavioral: Coping with ADHD through Relationships and Education **Label:** Coping with ADHD through Relationships and Education (CARE) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Parental Friendship Coaching (PFC) **Description:** In this condition, therapists instructed parents in ways to coach their children to display better friendship behaviors using skills teaching, role play, active practice, and homework. This is a 10 week group intervention. **Name:** Parental Friendship Coaching **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Coping with ADHD through Relationships and Education (CARE) **Description:** In this condition, the therapist provided parents with psychoeducation about ADHD and friendship difficulties, and encouraged them to apply this information to their child and to support one another with tips about how to address these problems. This is a 10 week group intervention. **Name:** Coping with ADHD through Relationships and Education **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Measures of positive and negative relationship quality with a friend, as reported by informants (adults, children) on the Friendship Quality Questionnaire **Measure:** Change in Positive and Negative Friendship Quality - Questionnaires **Time Frame:** change from baseline (pre-treatment) to post-treatment (approximately 4 months after baseline) **Description:** Measures of positive and negative relationship quality with a friend, as reported by informants (adults, children) on the Friendship Quality Questionnaire **Measure:** Change in Positive and Negative Friendship Quality - Questionnaires **Time Frame:** change from baseline (pre-treatment) to follow-up (approximately 12 months after baseline, and 4 months after post-treatment) **Description:** Measures of positive and negative relationship quality with a friend, as observed in a lab-based interaction **Measure:** Change in Positive and Negative Friendship Quality - Observations **Time Frame:** change from baseline (pre-treatment) to post-treatment (approximately 4 months after baseline) **Description:** Measures of positive and negative relationship quality with a friend, as observed in a lab-based interaction **Measure:** Change in Positive and Negative Friendship Quality - Observations **Time Frame:** change from baseline (pre-treatment) to follow-up (approximately 12 months after baseline, and 4 months after post-treatment) #### Secondary Outcomes **Description:** Measures of positive and negative behaviors with a friend, as reported by parents on the Quality of Play Questionnaire **Measure:** Change in Positive and Negative Friendship Behaviors- Questionnaires **Time Frame:** change from baseline (pre-treatment) to post-treatment (approximately 4 months after baseline) **Description:** Measures of positive and negative behaviors with a friend, as reported by parents on the Quality of Play Questionnaire **Measure:** Change in Positive and Negative Friendship Behaviors- Questionnaires **Time Frame:** change from baseline (pre-treatment) to follow-up (approximately 12 months after baseline, and 4 months after post-treatment) **Description:** Measures of positive and negative behaviors with a friend, as reported by parents and teachers on the Social Skills Informant System **Measure:** Change in Positive and Negative Friendship Behaviors- Questionnaires **Time Frame:** change from baseline (pre-treatment) to post-treatment (approximately 4 months after baseline) **Description:** Measures of positive and negative behaviors with a friend, as reported by parents and teachers on the Social Skills Informant System **Measure:** Change in Positive and Negative Friendship Behaviors- Questionnaires **Time Frame:** change from baseline (pre-treatment) to follow-up (approximately 12 months after baseline, and 4 months after post-treatment) **Description:** Measures of positive and negative behaviors with a friend, as observed in a lab-based interaction **Measure:** Change in Positive and Negative Friendship Behaviors- Observations **Time Frame:** change from baseline (pre-treatment) to post-treatment (approximately 4 months after baseline) **Description:** Measures of positive and negative behaviors with a friend, as observed in a lab-based interaction **Measure:** Change in Positive and Negative Friendship Behaviors- Observations **Time Frame:** change from baseline (pre-treatment) to follow-up (approximately 12 months after baseline, and 4 months after post-treatment) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Children who meet diagnostic criteria for ADHD * Children who are have peer relationship problems Exclusion Criteria: * Children with autism spectrum disorder, psychosis, or active suicidality (requires other interventions * Children with intellectual disability (may not benefit from the interventions offered) * Children who are not on a stable dose of medication (this treatment may affect outcome measures) * Children who are receiving other behavioral treatment or treatment for social problems (these other treatments may affect outcome measures). **Maximum Age:** 11 Years **Minimum Age:** 6 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** University of British Columbia **Name:** Amori Mikami, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Université du Québec en Outaouais **Name:** Sebastien Normand, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M4594 - Name: Attention Deficit Disorder with Hyperactivity - Relevance: LOW - As Found: Unknown - ID: M9999 - Name: Hyperkinesis - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00956579 **Brief Title:** Sensory and Connectivity Abnormalities in Autism Spectrum Disorders **Official Title:** MEG/EEG/MRI and Psychophysics Study of Developmental Disorders #### Organization Study ID Info **ID:** 2005P001768 #### Organization **Class:** OTHER **Full Name:** Massachusetts General Hospital #### Secondary ID Infos **ID:** 5R01MH117998 **Link:** https://reporter.nih.gov/quickSearch/5R01MH117998 **Type:** NIH ### Status Module #### Completion Date **Date:** 2023-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-09-18 **Type:** ACTUAL **Last Update Submit Date:** 2020-09-16 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2023-06 **Type:** ESTIMATED #### Start Date **Date:** 2013-06 **Type:** ACTUAL **Status Verified Date:** 2020-09 #### Study First Post Date **Date:** 2009-08-11 **Type:** ESTIMATED **Study First Submit Date:** 2007-10-23 **Study First Submit QC Date:** 2009-08-10 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institutes of Health (NIH) **Class:** NIH **Name:** National Institute of Mental Health (NIMH) #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Investigator Affiliation:** Massachusetts General Hospital **Investigator Full Name:** Tal Kenet **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Study the neural substrates of autism spectrum disorders using neuroimaging methods such as MEG/EEG/MRI. **Detailed Description:** (NOTE: we are currently recruiting individuals between the ages of 14 and 32, either typically developing or with an autism spectrum disorder.) To study how sensory information is processed by the brain, we primarily use an instrument called MEG (MagnetoEncephaloGraphy), which measures the magnetic brainwaves emitted by our brains. The device does not have any output (i.e., there is no magnetic field); it only measures the waves produced in the brain. We measure those waves as the participants in the study listen to, view, or otherwise experience simple, non painful, stimuli. For instance, participants may listen to words while sitting in the MEG room, and watching a movie with the sound turned off. We then combine this information with pictures of the brain from MRI (Magnetic Resonance Imaging - when available), to get an idea about both the anatomy and the function of the brain, so that we can study how the brains of populations with autism spectrum disorders or language disorders may be different from those of typically developing populations. ### Conditions Module **Conditions:** - Autism Spectrum Disorder **Keywords:** - autism - autistic - sensory - MEG - connectivity - brain - MRI - language - developmental - neurodevelopmental - aspergers - asperger's - coherence ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** OTHER #### Enrollment Info **Count:** 120 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** No intervention Healthy participants ages 14-32 for a neuroimaging study **Label:** Healthy individuals #### Arm Group 2 **Description:** No intervention ASD participants ages 14-32 for a neuroimaging study. **Label:** Individuals with Autism Spectrum Disorder ### Outcomes Module #### Primary Outcomes **Measure:** Saliency of Sensory Stimuli in Developmental Disorders **Time Frame:** up to 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All of the following criteria must be met by all participants: * The participant or the participant's legal guardian is able to understand and is willing to comply with the requirements of the study * The participant meets the age requirements (14-32 years old) * The participant or legal guardian has signed an Informed Consent Form specific to this study, and is able to understand the consent form. * The participant must have English as their first language. * The participant must have a non-verbal IQ \> 70 * For the ASD/language disorder group only: * Autism Spectrum Disorder: Participants must meet criteria for Autism Spectrum Disorder on the ADOS. Exclusion Criteria: * The following exclusion criteria apply to both control and autism groups: * Any volunteer for whom informed consent cannot be obtained * Volunteers with metal braces, extensive dental work involving metals, implanted electromagnetically activated medical equipment (cardiac pacemakers, neurostimulators, functioning infusion pumps), all of which would interfere with the MEG signal, will be excluded from the MEG portion of the study * Volunteers with any medically diagnosed sensory loss * Volunteers with a known genetic disorder (e.g. Tourette's syndrome, etc), or other medical condition affecting the brain, such as progressive encephalopathy as well as those who are on high doses of multiple anti-seizure medications and have frequent, uncontrolled seizures * Asphyxia at birth or any other time, premature birth (Fewer than 34 weeks gestation) * For the control group only: * Volunteers diagnosed with a mental condition such as depression, anxiety, aggression, hyperactivity, attention deficit disorder (with or without hyperactivity). * Volunteers who score below the autism spectrum cut-off (in the normal range) on the ADOS and SCQ * Volunteers on any sort of neuro-psychopharmacological treatment (including antidepressants, stimulants, antipsychotics, anticonvulsants, benzodiazepines). * For the autism group only: * Children or adults not meeting criteria for autism spectrum disorder * Volunteers with co-morbid disorders such as tuberous sclerosis or fragile X. **Healthy Volunteers:** True **Maximum Age:** 32 Years **Minimum Age:** 14 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** Adult/Pediatric ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** TRANSCEND@partners.org **Name:** Nicole McGuiggan, Rsch Coord **Phone:** 617-966-9766 **Role:** CONTACT #### Locations **Location 1:** **City:** Charlestown **Country:** United States **Facility:** Martinos Center or Biomedical Imaging **State:** Massachusetts **Status:** RECRUITING **Zip:** 02129 #### Overall Officials **Official 1:** **Affiliation:** Massachusetts General Hospital **Name:** Tal Kenet, Ph.D **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002659 - Term: Child Development Disorders, Pervasive - ID: D000065886 - Term: Neurodevelopmental Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth ### Condition Browse Module - Browse Leaves - ID: M4623 - Name: Autistic Disorder - Relevance: HIGH - As Found: Autism - ID: M206 - Name: Autism Spectrum Disorder - Relevance: HIGH - As Found: Autism Spectrum Disorder - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M5902 - Name: Developmental Disabilities - Relevance: LOW - As Found: Unknown - ID: M5903 - Name: Child Development Disorders, Pervasive - Relevance: LOW - As Found: Unknown - ID: M30644 - Name: Neurodevelopmental Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001321 - Term: Autistic Disorder - ID: D000067877 - Term: Autism Spectrum Disorder ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04779879 **Acronym:** COMET-PEAK **Brief Title:** Safety, Tolerability and Pharmacokinetics of Second Generation VIR-7831 Material in Non-hospitalized Participants With Mild to Moderate COVID-19 **Official Title:** A Multicenter, Randomized, Double-Blind, Parallel Group Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Second Generation VIR-7831 Material in Non-Hospitalized Participants With Mild to Moderate Coronavirus Disease 2019 (COVID-19) #### Organization Study ID Info **ID:** VIR-7831-5006 #### Organization **Class:** INDUSTRY **Full Name:** Vir Biotechnology, Inc. #### Secondary ID Infos **Domain:** GlaxoSmithKline **ID:** GSK Study 216912 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2022-04-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-04-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-08-20 **Type:** ACTUAL #### Results First Post Date **Date:** 2022-11-10 **Type:** ACTUAL **Results First Submit Date:** 2022-08-24 **Results First Submit QC Date:** 2022-10-13 #### Start Date **Date:** 2021-02-18 **Type:** ACTUAL **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2021-03-03 **Type:** ACTUAL **Study First Submit Date:** 2021-03-01 **Study First Submit QC Date:** 2021-03-01 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Lead Sponsor **Class:** INDUSTRY **Name:** Vir Biotechnology, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a phase 2 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 (Sotrovimab) Generation 1 (Gen1) or VIR-7831 (Sotrovimab) Generation 2 (Gen2) and will be assessed for safety, tolerability, and pharmacokinetics. ### Conditions Module **Conditions:** - Covid19 **Keywords:** - SARS-CoV-2 - coronavirus - coronavirus disease 2019 - COVID-19 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Masking Description:** Part A is double-blinded. Parts B and C are open label. **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 354 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Part A (double-blinded) participants will be randomized to receive 500 mg of an IV infusion of Sotrovimab Gen 1 material or 500 mg of an IV infusion of VIR-7831 Gen 2 material **Intervention Names:** - Biological: Sotrovimab (Gen1) - Biological: Sotrovimab (Gen2) **Label:** Sotrovimab (Gen1) **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Part B (open-label) participants will be randomized to receive 500 mg of Sotrovimab Gen2 material by IV infusion or by IM injection Part C (open-label) participants will be randomized to receive 500 mg of Sotrovimab Gen2 material by IV infusion or 250 mg by IM injection **Intervention Names:** - Biological: Sotrovimab (Gen2) **Label:** Sotrovimab (Gen2) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Sotrovimab (Gen1) **Description:** Participants will be randomized to receive an IV infusion of Sotrovimab Gen 1 material **Name:** Sotrovimab (Gen1) **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Sotrovimab (Gen2) **Description:** Participants will be randomized to receive Sotrovimab Gen2 material by IV infusion or by IM injection **Name:** Sotrovimab (Gen2) **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - Sotrovimab (Gen1) **Description:** Participants will be randomized to receive Sotrovimab Gen2 material by IV infusion **Name:** Sotrovimab (Gen2) **Type:** BIOLOGICAL ### Outcomes Module #### Other Outcomes **Description:** Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part A: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Time Frame:** Up to Day 28 **Description:** Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part B: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Time Frame:** Up to Day 28 **Description:** Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part C: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Time Frame:** Up to Day 28 **Description:** Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part A: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Time Frame:** Up to Day 28 **Description:** Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part B: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Time Frame:** Up to Day 28 **Description:** Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part C: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Time Frame:** Up to Day 28 **Description:** Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part A: Number of Participants With the Presence of Anti-VIR-7831 Antibody **Time Frame:** Up to Week 24 **Description:** Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part B: Number of Participants With the Presence of Anti-VIR-7831 Antibody **Time Frame:** Up to Week 24 **Description:** Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part C: Number of Participants With the Presence of Anti-VIR-7831 Antibody **Time Frame:** Up to Week 24 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibody using a validated electrochemiluminescent (ECL) immunoassay. The results for this outcome measure will never be posted. **Measure:** Part A: Titers of Anti-drug Antibody to VIR-7831 **Time Frame:** Up to Week 24 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibody using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part B: Titers of Anti-drug Antibody to VIR-7831 **Time Frame:** Up to Week 24 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibody using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part C: Titers of Anti-drug Antibody to VIR-7831 **Time Frame:** Up to Week 24 **Description:** Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part A: Number of Participants With the Presence of Anti-nucleocapsid (Anti-N), Anti-spike (Anti-S) and Anti-Receptor Binding Domain (Anti-RBD) SARS-CoV-2 Antibodies at Baseline **Time Frame:** Baseline (Day 1) **Description:** Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part B: Number of Participants With the Presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Time Frame:** Baseline (Day 1) **Description:** Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part C: Number of Participants With the Presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Time Frame:** Baseline (Day 1) **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part A: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Time Frame:** Baseline (Day 1) **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part B: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Time Frame:** Baseline (Day 1) **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part C: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Time Frame:** Baseline (Day 1) **Description:** Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part A: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29 **Time Frame:** Day 29 **Description:** Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part B: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29 **Time Frame:** Day 29 **Description:** Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Measure:** Part C: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29 **Time Frame:** Day 29 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part A: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29 **Time Frame:** Day 29 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part B: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29 **Time Frame:** Day 29 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Measure:** Part C: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29 **Time Frame:** Day 29 #### Primary Outcomes **Description:** An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Measure:** Part A: Number of Participants With All Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29 **Time Frame:** Up to Day 29 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion-related reactions (IRR) including hypersensitivity, events related to antibody-dependent enhancement, and events related to immunogenicity. **Measure:** Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 **Time Frame:** Up to Day 29 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. **Measure:** Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29 **Time Frame:** Up to Day 29 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Measure:** Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 **Time Frame:** Up to Day 29 **Description:** AUC of SARS-CoV-2 viral load was measured by Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from Day 1 to Day 8 in nasopharyngeal (NP) swab samples. Analysis was performed using an Analysis of covariance (ANCOVA) model with covariates of treatment and Baseline logarithm (base 10) viral load. **Measure:** Part B: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 (AUCD1-8) **Time Frame:** Day 1 to Day 8 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in NP swab samples. Analysis was performed using an ANCOVA model with covariates of treatment, and Baseline logarithm (base10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Measure:** Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8) **Time Frame:** Day 1 to Day 8 #### Secondary Outcomes **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events which were not Serious were considered as Non-Serious adverse events. **Measure:** Part A: Number of Participants With Non-Serious AEs Through Week 12 **Time Frame:** Up to Week 12 **Description:** A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Measure:** Part A: Number of Participants With SAEs Through Week 24 **Time Frame:** Up to Week 24 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs are infusion-related reactions (IRR) including hypersensitivity, events related to antibody-dependent enhancement, and events related to immunogenicity. **Measure:** Part A: Number of Participants With AESI Through Week 24 **Time Frame:** Up to Week 24 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. **Measure:** Part A: Number of Participants With Abnormal ECG Findings at Indicated Time Points **Time Frame:** Days 1, 5, 11 and 85 (Week 12) **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Measure:** Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Week 24 **Time Frame:** Up to Week 24 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. Adverse events include both Serious and Other Adverse Events. **Measure:** Part B: Number of Participants With All AEs and SAEs Through Day 29 **Time Frame:** Up to Day 29 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion/injection-related reactions (IRR) including hypersensitivity; injection site reactions (ISRs); events related to antibody-dependent enhancement; events related to immunogenicity. **Measure:** Part B: Number of Participants With AESI Through Day 29 **Time Frame:** Up to Day 29 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. **Measure:** Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 **Time Frame:** Up to Day 29 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Measure:** Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 **Time Frame:** Up to Day 29 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. Adverse events include both Serious and Other Adverse Events. **Measure:** Part C: Number of Participants With All AEs and SAEs Through Day 29 **Time Frame:** Up to Day 29 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. **Measure:** Part C: Number of Participants With AESI Through Day 29 **Time Frame:** Up to Day 29 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. **Measure:** Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 **Time Frame:** Up to Day 29 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Measure:** Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 **Time Frame:** Up to Day 29 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. **Measure:** Part B: Number of Participants With Non-Serious AEs Through Week 12 **Time Frame:** Up to Week 12 **Description:** A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Measure:** Part B: Number of Participants With SAEs Through Week 36 **Time Frame:** Up to Week 36 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs are infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. **Measure:** Part B: Number of Participants With AESI Through Week 36 **Time Frame:** up to Week 36 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. **Measure:** Part B: Number of Participants With Abnormal ECG Findings at Indicated Time Points **Time Frame:** Days 1, 5, 11 and 85 (Week 12) **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Measure:** Part B: Number of Participants With Disease Progression Events Through Week 36 **Time Frame:** Up to Week 36 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. **Measure:** Part C: Number of Participants With Non-Serious AEs Through Week 12 **Time Frame:** Up to Week 12 **Description:** A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Measure:** Part C: Number of Participants With SAEs Through Week 36 **Time Frame:** Up to Week 36 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs are infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. **Measure:** Part C: Number of Participants With AESI Through Week 36 **Time Frame:** Up to Week 36 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. **Measure:** Part C: Number of Participants With Abnormal ECG Findings at Indicated Time Points **Time Frame:** Days 1, 5, 11 and 85 (Week 12) **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Measure:** Part C: Number of Participants With Disease Progression Events Through Week 36 **Time Frame:** Up to Week 36 **Description:** SARS-CoV-2 viral load was based on saliva and nasal mid-turbinate swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the NEG and \<2.08 results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. **Measure:** Part A: Change From Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load **Time Frame:** Baseline, Days 2, 5, 8, 11, 15, 22 and 29 **Description:** Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the "NEG" and "\<2.08" results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. **Measure:** Part B: Change From Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples **Time Frame:** Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29 **Description:** Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the "NEG" and "\<2.08" results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. **Measure:** Part C: Change From Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples **Time Frame:** Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29 **Description:** Viral load was measured by qRT-PCR from nasopharyngeal swab samples. Viral load (log10 copies/mL) values recorded as negative were considered as undetectable viral load. Percentage of participants with undetectable viral load have been presented. Percentage values are rounded off. **Measure:** Part B: Percentage of Participants With Undetectable Viral Load **Time Frame:** Days 2, 3, 5, 8, 11, 15, 22 and 29 **Description:** Viral load was measured by qRT-PCR from nasopharyngeal swab samples. Viral load (log10 copies/mL) values recorded as negative were considered as undetectable viral load. Percentage of participants with undetectable viral load have been presented. Percentage values are rounded off. **Measure:** Part C: Percentage of Participants With Undetectable Viral Load **Time Frame:** Days 2, 3, 5, 8, 11, 15, 22 and 29 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 5. Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. **Measure:** Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) **Time Frame:** Day 1 to Day 5 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 11. Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. **Measure:** Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) **Time Frame:** Day 1 to Day 11 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 5. Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Measure:** Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) **Time Frame:** Day 1 to Day 5 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 11. Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Measure:** Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) **Time Frame:** Day 1 to Day 11 **Description:** Percentage of participants with a persistently high viral load were categorized as \>=4.1 log10 copies/mL and \<4.1 log10 copies/mL. Percentage of participants with a persistently high viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage of participants with a persistently high viral load at Day 8 has been presented. Percentage values are rounded off. **Measure:** Part B: Percentage of Participants With a Persistently High Viral Load at Day 8 **Time Frame:** Day 8 **Description:** Percentage of participants with a persistently high viral load were categorized as \>=4.1 log10 copies/mL and \<4.1 log10 copies/mL. Percentage of participants with a persistently high viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage of participants with a persistently high viral load at Day 8 has been presented. Percentage values are rounded off. **Measure:** Part C: Percentage of Participants With a Persistently High Viral Load at Day 8 **Time Frame:** Day 8 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Cmax of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Cmax of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Cmax of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Cmax of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Concentration at Last Quantifiable Time-point (Clast) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Clast of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Clast of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Clast of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Clast of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Time to Reach Cmax (Tmax) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Tmax of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Tmax of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Tmax of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Tmax of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Tlast of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Tlast of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Tlast of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Tlast of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: AUC From Day 1 to 29 (AUCD1-29) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: AUCD1-29 of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: AUCD1-29 of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: AUCD1-29 of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: AUCD1-29 of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUC[0-inf]) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: AUC(0-inf) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: AUC(0-inf) of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: AUC(0-inf) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: AUC(0-inf) of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: AUClast of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: AUClast of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: AUClast of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: AUClast of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Percentage of AUC(Infinity) Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: %AUCexp of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: %AUCexp of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: %AUCexp of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: %AUCexp of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: t1/2 of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: t1/2 of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: t1/2 of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: t1/2 of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Apparent Volume of Distribution During the Elimination Phase Following Intravascular Administrtion (Vz) of VIR-7831 **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Vz of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Apparent Volume of Distribution During the Elimination Phase Following Extravascular Administration (Vz/F) of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Vz of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Vz/F of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Vss of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: Vss of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part A: Clearance (CL) of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: CL of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part B: Apparent Clearance (CL/F) of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: CL of VIR-7831 After IV Administration **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Part C: CL/F of VIR-7831 After IM Administration **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Dose-normalized least square geometric mean ratio of AUCinf was derived based on collected assessments up to 169 (+/-7 days) for Part B- Sotrovimab Gen2: 500 mg IV arm, and up to 169 (+/-18 days) for Part C- Sotrovimab Gen2: 500 mg IV arm. **Measure:** Dose-normalized Least Square Geometric Mean Ratio of AUCinf for VIR-7831 Gen2 Between the Three Dose Levels (250 mg IM in Part C, 500 mg IM in Part B and 500 mg IV in Parts B and C) **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Dose-normalized Least Square Geometric Mean Ratio of AUCinf for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Dose-normalized Least Square Geometric Mean Ratio of AUClast for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Dose-normalized Least Square Geometric Mean Ratio of AUCD1-D29 for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Measure:** Dose-normalized Least Square Geometric Mean Ratio of Cmax for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * For Part A, participants must be aged 18 years or older at the time of obtaining informed consent * For Parts B and C, participants must be aged between 18 years and 69 years old at the time of obtaining informed consent * Participants who have a positive SARS-CoV-2 test result ≤7 days prior to enrollment and oxygen saturation ≥94% on room air and have COVID-19 symptoms and ≤7 days from onset of symptoms Exclusion Criteria: * Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours * Symptoms consistent with severe COVID-19 * Participants who, in the judgement of the investigator are likely to die in the next 7 days. * Severely immunocompromised participants * For Parts A and B, prior receipt of a SARS-CoV-2 vaccine at any time prior to enrollment (vaccination with an authorized or approved SARS-CoV-2 vaccine will not be allowed for 90 days after dosing) * For Parts B and C, conditions that would prohibit receipt of IM injections in the investigator's opinion * For Parts A, B and C, receipt of any vaccine within 48 hours prior to enrollment (vaccination with an authorized or approved SARS-CoV-2 vaccine will not be allowed for 90 days after dosing) **Maximum Age:** 69 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Anniston **Country:** United States **Facility:** Investigative Site **State:** Alabama **Zip:** 36207 **Location 2:** **City:** Bakersfield **Country:** United States **Facility:** Investigative Site **State:** California **Zip:** 93301 **Location 3:** **City:** Northridge **Country:** United States **Facility:** Investigative Site **State:** California **Zip:** 91325 **Location 4:** **City:** Fort Pierce **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 34982 **Location 5:** **City:** Gainesville **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 32607 **Location 6:** **City:** Hialeah **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33016 **Location 7:** **City:** Miami **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33125 **Location 8:** **City:** Miami **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33135 **Location 9:** **City:** Miami **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33155 **Location 10:** **City:** Miami **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33176 **Location 11:** **City:** Orlando **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 32803 **Location 12:** **City:** Pembroke Pines **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33024 **Location 13:** **City:** Tampa **Country:** United States **Facility:** Investigative Site **State:** Florida **Zip:** 33614 **Location 14:** **City:** Columbus **Country:** United States **Facility:** Investigative Site **State:** Georgia **Zip:** 31904 **Location 15:** **City:** Winfield **Country:** United States **Facility:** Investigative Site **State:** Illinois **Zip:** 60190 **Location 16:** **City:** Rockville **Country:** United States **Facility:** Investigative Site **State:** Maryland **Zip:** 20850 **Location 17:** **City:** Bronx **Country:** United States **Facility:** Investigative Site **State:** New York **Zip:** 10456 **Location 18:** **City:** Houston **Country:** United States **Facility:** Investigative Site **State:** Texas **Zip:** 77090 **Location 19:** **City:** Sarnia **Country:** Canada **Facility:** Investigative Site **State:** Ontario **Zip:** N7T 4X3 **Location 20:** **City:** Toronto **Country:** Canada **Facility:** Investigative Site **State:** Ontario **Zip:** M9V 4B4 **Location 21:** **City:** Milano **Country:** Italy **Facility:** Investigative Site **Zip:** 20132 **Location 22:** **City:** Daejeon **Country:** Korea, Republic of **Facility:** Investigative Site **Zip:** 35015 **Location 23:** **City:** Alicante **Country:** Spain **Facility:** Investigative Site **Zip:** 03010 **Location 24:** **City:** Barcelona **Country:** Spain **Facility:** Investigative Site **Zip:** 08006 **Location 25:** **City:** Centelles **Country:** Spain **Facility:** Investigative Site **Zip:** 08540 **Location 26:** **City:** Granada **Country:** Spain **Facility:** Investigative Site **Zip:** 18014 **Location 27:** **City:** La Roca Del Vallès **Country:** Spain **Facility:** Investigative Site **Zip:** 08430 **Location 28:** **City:** Madrid **Country:** Spain **Facility:** Investigative Site **Zip:** 28031 **Location 29:** **City:** Madrid **Country:** Spain **Facility:** Investigative Site **Zip:** 28040 **Location 30:** **City:** Pozuelo De Alarcón **Country:** Spain **Facility:** Investigative Site **Zip:** 28223 **Location 31:** **City:** Vigo **Country:** Spain **Facility:** Investigative Site **Zip:** 36312 ### References Module #### References **Citation:** Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2. **PMID:** 34473343 ## Document Section ### Large Document Module #### Large Docs - Date: 2021-10-29 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1381436 - Type Abbrev: Prot - Upload Date: 2022-08-16T17:33 - Date: 2022-03-15 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 787503 - Type Abbrev: SAP - Upload Date: 2022-08-16T17:33 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 ### Intervention Browse Module - Ancestors - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M349835 - Name: Sotrovimab - Relevance: HIGH - As Found: Viscosity - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000711967 - Term: Sotrovimab ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2022-09-22 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Safety Population consisted of all randomized participants who were exposed to study intervention. #### Event Groups **Group ID:** EG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV **Deaths Num At Risk:** 8 **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** EG000 **Other Num at Risk:** 8 **Serious Number At Risk:** 8 **Title:** Part A-Sotrovimab Gen1: 500 mg IV **Group ID:** EG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV **Deaths Num At Risk:** 22 **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** EG001 **Other Num Affected:** 6 **Other Num at Risk:** 22 **Serious Number At Risk:** 22 **Title:** Part A- Sotrovimab Gen2: 500 mg IV **Group ID:** EG002 **Title:** Part B- Sotrovimab Gen2: 500 mg IV **Deaths Num At Risk:** 84 **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** EG002 **Other Num Affected:** 8 **Other Num at Risk:** 84 **Serious Number Affected:** 1 **Serious Number At Risk:** 84 **Title:** Part B- Sotrovimab Gen2: 500 mg IV **Group ID:** EG003 **Title:** Part B- Sotrovimab Gen2: 500 mg IM **Deaths Num At Risk:** 82 **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** EG003 **Other Num Affected:** 20 **Other Num at Risk:** 82 **Serious Number Affected:** 2 **Serious Number At Risk:** 82 **Title:** Part B- Sotrovimab Gen2: 500 mg IM **Group ID:** EG004 **Title:** Part C- Sotrovimab Gen2: 500 mg IV **Deaths Num At Risk:** 79 **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** EG004 **Other Num Affected:** 16 **Other Num at Risk:** 79 **Serious Number Affected:** 2 **Serious Number At Risk:** 79 **Title:** Part C- Sotrovimab Gen2: 500 mg IV **Group ID:** EG005 **Title:** Part C- Sotrovimab Gen2: 250 mg IM **Deaths Num Affected:** 1 **Deaths Num At Risk:** 78 **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** EG005 **Other Num Affected:** 16 **Other Num at Risk:** 78 **Serious Number Affected:** 3 **Serious Number At Risk:** 78 **Title:** Part C- Sotrovimab Gen2: 250 mg IM **Frequency Threshold:** 1 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Iron deficiency anemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Motion sickness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA 24.0 **Term:** vertigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Episcleritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Abdominal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Aphthous ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Dyspepsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Paraesthesia Oral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Uvulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Feeling abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Influenza like illness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Injection site discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** General disorders and administration site conditions **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Injection site nodule **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** General disorders and administration site conditions **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Injection site pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** General disorders and administration site conditions **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Peripheral swelling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** General disorders and administration site conditions **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Hypertransaminasaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Acute sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Blister infected **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Conjunctivitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Folliculitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Helicobacter gastritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Herpes simplex **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Herpes zoster **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Otitis media acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Pharyngitis streptococcal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.0 **Term:** Limb injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.0 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 24.0 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 24.0 **Term:** Brain natriuretic peptide increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 24.0 **Term:** Hepatic enzyme increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 24.0 **Term:** Lipase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 24.0 **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Gout **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Hyperlipasaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Vitamin D deficiency **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Pain in jaw **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Migraine **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Restless legs syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Conversion disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Acute respiratory failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Oropharyngeal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Rhinorrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Sleep apnoea syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Urticaria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.0 **Term:** Superficial vein thrombosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.0 #### Serious Events **Term:** COVID-19 pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 8 **Group ID:** EG001 **Num At Risk:** 22 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 84 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 82 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 79 **Num Events:** 1 **Group ID:** EG005 **Num Affected:** 3 **Num At Risk:** 78 **Num Events:** 3 **Term:** Coronavirus pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 8 **Group ID:** EG001 **Num At Risk:** 22 **Group ID:** EG002 **Num At Risk:** 84 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 79 **Group ID:** EG005 **Num At Risk:** 78 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 8 **Group ID:** EG001 **Num At Risk:** 22 **Group ID:** EG002 **Num At Risk:** 84 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 79 **Group ID:** EG005 **Num At Risk:** 78 **Term:** Incisional hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 8 **Group ID:** EG001 **Num At Risk:** 22 **Group ID:** EG002 **Num At Risk:** 84 **Group ID:** EG003 **Num At Risk:** 82 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 79 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 78 **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 8 **Group ID:** EG001 **Num At Risk:** 22 **Group ID:** EG002 **Num At Risk:** 84 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 79 **Group ID:** EG005 **Num At Risk:** 78 **Term:** Acute respiratory failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 8 **Group ID:** EG001 **Num At Risk:** 22 **Group ID:** EG002 **Num At Risk:** 84 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 79 **Group ID:** EG005 **Num At Risk:** 78 **Time Frame:** All-cause mortality, non-serious AEs and SAEs were collected up to Week 24 in Part A; and up to Week 36 in Parts B and C of the study ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 8 **Group ID:** BG001 **Value:** 22 **Group ID:** BG002 **Value:** 84 **Group ID:** BG003 **Value:** 82 **Group ID:** BG004 **Value:** 79 **Group ID:** BG005 **Value:** 78 **Group ID:** BG006 **Value:** 353 **Units:** Participants ### Group **ID:** BG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. ### Group **ID:** BG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. ### Group **ID:** BG002 **Title:** Part B- Sotrovimab Gen2: 500 mg IV **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. ### Group **ID:** BG003 **Title:** Part B- Sotrovimab Gen2: 500 mg IM **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. ### Group **ID:** BG004 **Title:** Part C- Sotrovimab Gen2: 500 mg IV **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. ### Group **ID:** BG005 **Title:** Part C- Sotrovimab Gen2: 250 mg IM **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. ### Group **ID:** BG006 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 2 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 80 #### Measurement **Group ID:** BG003 **Value:** 76 #### Measurement **Group ID:** BG004 **Value:** 77 #### Measurement **Group ID:** BG005 **Value:** 74 #### Measurement **Group ID:** BG006 **Value:** 335 **Category Title:** 19-64 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 2 #### Measurement **Group ID:** BG005 **Value:** 4 #### Measurement **Group ID:** BG006 **Value:** 16 **Category Title:** >=65 years **Class Title:** Participants ### Measure #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 45 #### Measurement **Group ID:** BG003 **Value:** 42 #### Measurement **Group ID:** BG004 **Value:** 39 #### Measurement **Group ID:** BG005 **Value:** 42 #### Measurement **Group ID:** BG006 **Value:** 183 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 39 #### Measurement **Group ID:** BG003 **Value:** 40 #### Measurement **Group ID:** BG004 **Value:** 40 #### Measurement **Group ID:** BG005 **Value:** 36 #### Measurement **Group ID:** BG006 **Value:** 170 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 7 #### Measurement **Group ID:** BG005 **Value:** 9 #### Measurement **Group ID:** BG006 **Value:** 24 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 21 #### Measurement **Group ID:** BG002 **Value:** 62 #### Measurement **Group ID:** BG003 **Value:** 64 #### Measurement **Group ID:** BG004 **Value:** 66 #### Measurement **Group ID:** BG005 **Value:** 63 #### Measurement **Group ID:** BG006 **Value:** 282 **Category Title:** White - White/Caucasian/European Heritage #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 6 #### Measurement **Group ID:** BG005 **Value:** 5 #### Measurement **Group ID:** BG006 **Value:** 16 **Category Title:** White - Arabic/North African Heritage #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 4 **Category Title:** Asian - East Asian Heritage #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 11 #### Measurement **Group ID:** BG003 **Value:** 13 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 24 **Category Title:** Asian - South East Asian Heritage #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 1 **Category Title:** Asian - Central/South Asian Heritage #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 1 #### Measurement **Group ID:** BG006 **Value:** 1 **Category Title:** American Indian Or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 1 **Category Title:** Mixed Asian Race **Class Title:** Participants **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Description:** Safety Population consisted of all randomized participants who were exposed to study intervention. **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Customized **Unit of Measure:** Participants ### Measure 2 **Description:** Safety Population consisted of all randomized participants who were exposed to study intervention. **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Description:** Safety Population consisted of all randomized participants who were exposed to study intervention. **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Restrictive Agreement:** True ### Point of Contact **Email:** clinicaltrials@vir.bio **Organization:** Vir Biotechnology, Inc. **Phone:** 415-654-5281 **Title:** Study Inquiry ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 #### Analysis **CI Lower Limit:** 0.98 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Analysis was performed using an Analysis of covariance (ANCOVA) model with covariates of treatment and Baseline logarithm (base 10) viral load. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.04 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 0.94 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Analysis was performed using an ANCOVA model with covariates of treatment, and Baseline logarithm (base10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.02 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 ### Outcome Measure 18 ### Outcome Measure 19 ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ### Outcome Measure 24 ### Outcome Measure 25 ### Outcome Measure 26 ### Outcome Measure 27 ### Outcome Measure 28 ### Outcome Measure 29 ### Outcome Measure 30 ### Outcome Measure 31 ### Outcome Measure 32 ### Outcome Measure 33 ### Outcome Measure 34 ### Outcome Measure 35 #### Analysis **CI Lower Limit:** 1.00 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.05 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 36 #### Analysis **CI Lower Limit:** 0.97 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.07 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.02 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 37 #### Analysis **CI Lower Limit:** 0.93 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.01 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 38 #### Analysis **CI Lower Limit:** 0.94 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.10 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.02 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 39 ### Outcome Measure 40 ### Outcome Measure 41 ### Outcome Measure 42 ### Outcome Measure 43 ### Outcome Measure 44 ### Outcome Measure 45 ### Outcome Measure 46 ### Outcome Measure 47 ### Outcome Measure 48 ### Outcome Measure 49 ### Outcome Measure 50 ### Outcome Measure 51 ### Outcome Measure 52 ### Outcome Measure 53 ### Outcome Measure 54 ### Outcome Measure 55 ### Outcome Measure 56 ### Outcome Measure 57 ### Outcome Measure 58 ### Outcome Measure 59 ### Outcome Measure 60 ### Outcome Measure 61 ### Outcome Measure 62 ### Outcome Measure 63 ### Outcome Measure 64 ### Outcome Measure 65 ### Outcome Measure 66 ### Outcome Measure 67 ### Outcome Measure 68 ### Outcome Measure 69 ### Outcome Measure 70 ### Outcome Measure 71 ### Outcome Measure 72 ### Outcome Measure 73 ### Outcome Measure 74 ### Outcome Measure 75 ### Outcome Measure 76 ### Outcome Measure 77 ### Outcome Measure 78 ### Outcome Measure 79 ### Outcome Measure 80 ### Outcome Measure 81 ### Outcome Measure 82 ### Outcome Measure 83 ### Outcome Measure 84 ### Outcome Measure 85 ### Outcome Measure 86 ### Outcome Measure 87 ### Outcome Measure 88 ### Outcome Measure 89 ### Outcome Measure 90 ### Outcome Measure 91 ### Outcome Measure 92 ### Outcome Measure 93 ### Outcome Measure 94 ### Outcome Measure 95 ### Outcome Measure 96 ### Outcome Measure 97 ### Outcome Measure 98 ### Outcome Measure 99 #### Analysis **CI Lower Limit:** 0.48 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.89 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Drug bioavailability was analyzed using an ANCOVA model with treatment and weight at Baseline as covariates. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 0.66 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.79 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Drug bioavailability was analyzed using an ANCOVA model with treatment and weight at Baseline as covariates. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 0.58 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 100 #### Analysis **CI Lower Limit:** 0.67 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.95 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dose proportionality was analyzed using an ANOVA model with treatment (250mg, 500mg) as a covariate, for each parameter of interest. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.14 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 101 #### Analysis **CI Lower Limit:** 0.69 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.62 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dose proportionality was analyzed using an ANOVA model with treatment (250mg, 500mg) as a covariate, for each parameter of interest. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.06 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 102 #### Analysis **CI Lower Limit:** 0.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.82 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dose proportionality was analyzed using an ANOVA model with treatment (250mg, 500mg) as a covariate, for each parameter of interest. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.11 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 103 #### Analysis **CI Lower Limit:** 0.77 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 2.12 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dose proportionality was analyzed using an ANOVA model with treatment (250mg, 500mg) as a covariate, for each parameter of interest. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of geometric least squares mean **Parameter Value:** 1.28 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 104 ### Outcome Measure 105 ### Outcome Measure 106 ### Outcome Measure 107 ### Outcome Measure 108 ### Outcome Measure 109 ### Outcome Measure 110 ### Outcome Measure 111 ### Outcome Measure 112 ### Outcome Measure 113 ### Outcome Measure 114 ### Outcome Measure 115 ### Outcome Measure 116 ### Outcome Measure 117 ### Outcome Measure 118 ### Outcome Measure 119 ### Outcome Measure 120 ### Outcome Measure 121 ### Outcome Measure 122 ### Outcome Measure 123 ### Outcome Measure 124 ### Outcome Measure 125 ### Outcome Measure 126 ### Outcome Measure 127 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 23.53 - **Spread:** - **Upper Limit:** 25.31 - **Value:** 24.40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 24.38 - **Spread:** - **Upper Limit:** 26.21 - **Value:** 25.28 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 24.68 - **Spread:** - **Upper Limit:** 27.81 - **Value:** 26.20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 25.26 - **Spread:** - **Upper Limit:** 28.27 - **Value:** 26.72 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 7 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 7 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 7 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 7 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 8 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 8 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 8 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 8 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 84 - **Group ID:** OG001 - **Value:** 82 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 84 - **Group ID:** OG001 - **Value:** 82 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 80 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 80 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 82 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 82 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 78 - **Group ID:** OG001 - **Value:** 79 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 78 - **Group ID:** OG001 - **Value:** 79 **Units:** Participants #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 25 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** #### Outcome Measure 26 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 27 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 28 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 76 - **Group ID:** OG001 - **Value:** 74 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 76 - **Group ID:** OG001 - **Value:** 74 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 72 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 72 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 73 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 73 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants #### Outcome Measure 29 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** #### Outcome Measure 30 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.4290 - **Upper Limit:** - **Value:** -0.270 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.9201 - **Upper Limit:** - **Value:** -1.114 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.3404 - **Upper Limit:** - **Value:** -0.780 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.0199 - **Upper Limit:** - **Value:** -2.620 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 3 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5689 - **Upper Limit:** - **Value:** -0.507 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.4982 - **Upper Limit:** - **Value:** -2.605 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 3 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5940 - **Upper Limit:** - **Value:** -1.043 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3963 - **Upper Limit:** - **Value:** -2.881 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 10 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.3444 - **Upper Limit:** - **Value:** -0.610 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.2132 - **Upper Limit:** - **Value:** -3.179 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5940 - **Upper Limit:** - **Value:** -1.043 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3210 - **Upper Limit:** - **Value:** -3.284 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5940 - **Upper Limit:** - **Value:** -1.043 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3123 - **Upper Limit:** - **Value:** -3.223 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.9726 - **Upper Limit:** - **Value:** -1.252 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.2277 - **Upper Limit:** - **Value:** -1.006 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 5 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.1230 - **Upper Limit:** - **Value:** -1.755 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.2100 - **Upper Limit:** - **Value:** -2.111 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.7839 - **Upper Limit:** - **Value:** -1.705 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7842 - **Upper Limit:** - **Value:** -2.703 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.3363 - **Upper Limit:** - **Value:** -2.810 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.5656 - **Upper Limit:** - **Value:** -2.923 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 5 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.3243 - **Upper Limit:** - **Value:** -2.490 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7103 - **Upper Limit:** - **Value:** -3.445 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 5 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2826 - **Upper Limit:** - **Value:** -2.668 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.9434 - **Upper Limit:** - **Value:** -3.873 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 5 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.3363 - **Upper Limit:** - **Value:** -2.810 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.8030 - **Upper Limit:** - **Value:** -3.752 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 5 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants #### Outcome Measure 31 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.1558 - **Upper Limit:** - **Value:** -1.146 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.1518 - **Upper Limit:** - **Value:** -0.611 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 63 - **Group ID:** OG001 - **Value:** 68 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2033 - **Upper Limit:** - **Value:** -1.438 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3132 - **Upper Limit:** - **Value:** -1.306 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 63 - **Group ID:** OG001 - **Value:** 66 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2480 - **Upper Limit:** - **Value:** -2.578 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.1655 - **Upper Limit:** - **Value:** -2.352 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.4553 - **Upper Limit:** - **Value:** -3.069 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.4193 - **Upper Limit:** - **Value:** -3.254 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 64 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.7148 - **Upper Limit:** - **Value:** -3.522 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.4907 - **Upper Limit:** - **Value:** -3.574 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 63 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.7443 - **Upper Limit:** - **Value:** -3.705 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.5525 - **Upper Limit:** - **Value:** -3.733 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 66 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.7994 - **Upper Limit:** - **Value:** -3.831 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7476 - **Upper Limit:** - **Value:** -3.778 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 64 - **Group ID:** OG001 - **Value:** 66 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8253 - **Upper Limit:** - **Value:** -3.933 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7455 - **Upper Limit:** - **Value:** -3.857 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants #### Outcome Measure 32 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.3835 - **Upper Limit:** - **Value:** -0.429 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3273 - **Upper Limit:** - **Value:** -0.519 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 59 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.5202 - **Upper Limit:** - **Value:** -0.905 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.6172 - **Upper Limit:** - **Value:** -1.123 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 50 - **Group ID:** OG001 - **Value:** 57 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9648 - **Upper Limit:** - **Value:** -2.076 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.0218 - **Upper Limit:** - **Value:** -1.967 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 57 - **Group ID:** OG001 - **Value:** 62 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8234 - **Upper Limit:** - **Value:** -3.122 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.8324 - **Upper Limit:** - **Value:** -3.180 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 55 - **Group ID:** OG001 - **Value:** 62 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.6870 - **Upper Limit:** - **Value:** -3.617 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.8168 - **Upper Limit:** - **Value:** -3.738 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 52 - **Group ID:** OG001 - **Value:** 61 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8248 - **Upper Limit:** - **Value:** -3.719 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.8148 - **Upper Limit:** - **Value:** -3.836 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 50 - **Group ID:** OG001 - **Value:** 61 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.7647 - **Upper Limit:** - **Value:** -3.693 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7492 - **Upper Limit:** - **Value:** -3.956 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 55 - **Group ID:** OG001 - **Value:** 65 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8167 - **Upper Limit:** - **Value:** -3.761 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7189 - **Upper Limit:** - **Value:** -3.963 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 56 - **Group ID:** OG001 - **Value:** 63 **Units:** Participants #### Outcome Measure 33 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 63 - **Group ID:** OG001 - **Value:** 68 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 63 - **Group ID:** OG001 - **Value:** 66 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 64 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 58 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 63 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 73 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 66 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 73 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 64 - **Group ID:** OG001 - **Value:** 66 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 81 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants #### Outcome Measure 34 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 59 - **Group ID:** OG001 - **Value:** 64 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 50 - **Group ID:** OG001 - **Value:** 57 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 57 - **Group ID:** OG001 - **Value:** 62 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 55 - **Group ID:** OG001 - **Value:** 62 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 63 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 52 - **Group ID:** OG001 - **Value:** 61 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 50 - **Group ID:** OG001 - **Value:** 61 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 88 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 55 - **Group ID:** OG001 - **Value:** 65 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 88 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 86 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 56 - **Group ID:** OG001 - **Value:** 63 **Units:** Participants #### Outcome Measure 35 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 15.53 - **Spread:** - **Upper Limit:** 16.77 - **Value:** 16.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 16.34 - **Spread:** - **Upper Limit:** 17.62 - **Value:** 16.97 **Title:** #### Outcome Measure 36 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 30.60 - **Spread:** - **Upper Limit:** 32.82 - **Value:** 31.69 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 31.28 - **Spread:** - **Upper Limit:** 33.53 - **Value:** 32.39 **Title:** #### Outcome Measure 37 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16.49 - **Spread:** - **Upper Limit:** 18.41 - **Value:** 17.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 16.66 - **Spread:** - **Upper Limit:** 18.51 - **Value:** 17.56 **Title:** #### Outcome Measure 38 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 31.17 - **Spread:** - **Upper Limit:** 34.97 - **Value:** 33.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 31.89 - **Spread:** - **Upper Limit:** 35.47 - **Value:** 33.63 **Title:** #### Outcome Measure 39 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89 **Title:** #### Outcome Measure 40 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 87 **Title:** #### Outcome Measure 41 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 48.28 - **Upper Limit:** - **Value:** 147.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 77.61 - **Upper Limit:** - **Value:** 204.7 **Title:** #### Outcome Measure 42 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 40.80 - **Upper Limit:** - **Value:** 156.5 **Title:** #### Outcome Measure 43 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.66 - **Upper Limit:** - **Value:** 28.8 **Title:** #### Outcome Measure 44 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 32.97 - **Upper Limit:** - **Value:** 137.4 **Title:** #### Outcome Measure 45 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.61 - **Upper Limit:** - **Value:** 11.1 **Title:** #### Outcome Measure 46 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.16 - **Upper Limit:** - **Value:** 6.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.17 - **Upper Limit:** - **Value:** 8.1 **Title:** #### Outcome Measure 47 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.48 - **Upper Limit:** - **Value:** 7.0 **Title:** #### Outcome Measure 48 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.65 - **Upper Limit:** - **Value:** 7.9 **Title:** #### Outcome Measure 49 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.59 - **Upper Limit:** - **Value:** 10.5 **Title:** #### Outcome Measure 50 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.73 - **Upper Limit:** - **Value:** 2.6 **Title:** #### Outcome Measure 51 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.04 - **Spread:** - **Upper Limit:** 0.38 - **Value:** 0.042 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.04 - **Spread:** - **Upper Limit:** 0.38 - **Value:** 0.042 **Title:** #### Outcome Measure 52 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.01 - **Spread:** - **Upper Limit:** 0.03 - **Value:** 0.026 **Title:** #### Outcome Measure 53 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.68 - **Spread:** - **Upper Limit:** 56.66 - **Value:** 6.878 **Title:** #### Outcome Measure 54 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.01 - **Spread:** - **Upper Limit:** 0.02 - **Value:** 0.014 **Title:** #### Outcome Measure 55 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 13.88 - **Spread:** - **Upper Limit:** 56.04 - **Value:** 27.866 **Title:** #### Outcome Measure 56 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 160.89 - **Spread:** - **Upper Limit:** 174.95 - **Value:** 161.333 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 160.70 - **Spread:** - **Upper Limit:** 180.15 - **Value:** 162.248 **Title:** #### Outcome Measure 57 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 160.76 - **Spread:** - **Upper Limit:** 175.68 - **Value:** 167.715 **Title:** #### Outcome Measure 58 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 55.68 - **Spread:** - **Upper Limit:** 175.66 - **Value:** 167.670 **Title:** #### Outcome Measure 59 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 27.79 - **Spread:** - **Upper Limit:** 185.75 - **Value:** 162.458 **Title:** #### Outcome Measure 60 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 160.97 - **Spread:** - **Upper Limit:** 180.83 - **Value:** 168.912 **Title:** #### Outcome Measure 61 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 392.56 - **Upper Limit:** - **Value:** 1355.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 308.31 - **Upper Limit:** - **Value:** 1738.8 **Title:** #### Outcome Measure 62 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 296.96 - **Upper Limit:** - **Value:** 1442.9 **Title:** #### Outcome Measure 63 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 376.78 - **Upper Limit:** - **Value:** 686.9 **Title:** #### Outcome Measure 64 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 528.26 - **Upper Limit:** - **Value:** 1405.4 **Title:** #### Outcome Measure 65 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 242.84 - **Upper Limit:** - **Value:** 327.1 **Title:** #### Outcome Measure 66 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1289.19 - **Upper Limit:** - **Value:** 3982.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 966.33 - **Upper Limit:** - **Value:** 5238.4 **Title:** #### Outcome Measure 67 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1123.41 - **Upper Limit:** - **Value:** 4449.3 **Title:** #### Outcome Measure 68 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1617.36 - **Upper Limit:** - **Value:** 3194.4 **Title:** #### Outcome Measure 69 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1369.36 - **Upper Limit:** - **Value:** 4255.3 **Title:** #### Outcome Measure 70 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 985.65 - **Upper Limit:** - **Value:** 1441.0 **Title:** #### Outcome Measure 71 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1086.56 - **Upper Limit:** - **Value:** 3456.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 826.89 - **Upper Limit:** - **Value:** 4528.5 **Title:** #### Outcome Measure 72 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 899.51 - **Upper Limit:** - **Value:** 3848.5 **Title:** #### Outcome Measure 73 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1249.20 - **Upper Limit:** - **Value:** 2446.5 **Title:** #### Outcome Measure 74 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1257.27 - **Upper Limit:** - **Value:** 3492.6 **Title:** #### Outcome Measure 75 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 763.78 - **Upper Limit:** - **Value:** 1185.8 **Title:** #### Outcome Measure 76 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.81 - **Upper Limit:** - **Value:** 14.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.42 - **Upper Limit:** - **Value:** 12.6 **Title:** #### Outcome Measure 77 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.92 - **Upper Limit:** - **Value:** 13.1 **Title:** #### Outcome Measure 78 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.35 - **Upper Limit:** - **Value:** 15.0 **Title:** #### Outcome Measure 79 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.29 - **Upper Limit:** - **Value:** 13.6 **Title:** #### Outcome Measure 80 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.11 - **Upper Limit:** - **Value:** 15.0 **Title:** #### Outcome Measure 81 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 53.98 - **Spread:** - **Upper Limit:** 68.09 - **Value:** 63.196 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 42.34 - **Spread:** - **Upper Limit:** 72.09 - **Value:** 55.547 **Title:** #### Outcome Measure 82 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 47.33 - **Spread:** - **Upper Limit:** 66.86 - **Value:** 55.735 **Title:** #### Outcome Measure 83 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 51.95 - **Spread:** - **Upper Limit:** 65.83 - **Value:** 59.347 **Title:** #### Outcome Measure 84 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 42.96 - **Spread:** - **Upper Limit:** 70.84 - **Value:** 60.938 **Title:** #### Outcome Measure 85 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 46.84 - **Spread:** - **Upper Limit:** 68.43 - **Value:** 61.867 **Title:** #### Outcome Measure 86 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.625 - **Upper Limit:** - **Value:** 12.40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.374 - **Upper Limit:** - **Value:** 7.88 **Title:** #### Outcome Measure 87 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.865 - **Upper Limit:** - **Value:** 9.97 **Title:** #### Outcome Measure 88 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.752 - **Upper Limit:** - **Value:** 18.14 **Title:** #### Outcome Measure 89 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.574 - **Upper Limit:** - **Value:** 10.93 **Title:** #### Outcome Measure 90 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.205 - **Upper Limit:** - **Value:** 20.24 **Title:** #### Outcome Measure 91 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.110 - **Upper Limit:** - **Value:** 11.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.232 - **Upper Limit:** - **Value:** 7.47 **Title:** #### Outcome Measure 92 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.514 - **Upper Limit:** - **Value:** 9.41 **Title:** #### Outcome Measure 93 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.973 - **Upper Limit:** - **Value:** 10.61 **Title:** #### Outcome Measure 94 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 42.88 - **Upper Limit:** - **Value:** 136.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.62 - **Upper Limit:** - **Value:** 98.7 **Title:** #### Outcome Measure 95 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 35.96 - **Upper Limit:** - **Value:** 120.3 **Title:** #### Outcome Measure 96 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 162.28 - **Upper Limit:** - **Value:** 216.2 **Title:** #### Outcome Measure 97 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 47.83 - **Upper Limit:** - **Value:** 130.5 **Title:** #### Outcome Measure 98 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 125.67 - **Upper Limit:** - **Value:** 237.8 **Title:** #### Outcome Measure 99 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.25 - **Spread:** - **Upper Limit:** 7.16 - **Value:** 5.52 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3.75 - **Spread:** - **Upper Limit:** 6.30 - **Value:** 4.86 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 7.12 - **Spread:** - **Upper Limit:** 9.90 - **Value:** 8.40 **Title:** #### Outcome Measure 100 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.81 - **Spread:** - **Upper Limit:** 8.11 - **Value:** 5.56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3.33 - **Spread:** - **Upper Limit:** 7.09 - **Value:** 4.86 **Title:** #### Outcome Measure 101 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.21 - **Spread:** - **Upper Limit:** 5.77 - **Value:** 4.31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2.98 - **Spread:** - **Upper Limit:** 5.51 - **Value:** 4.05 **Title:** #### Outcome Measure 102 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.83 - **Spread:** - **Upper Limit:** 1.65 - **Value:** 1.17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.74 - **Spread:** - **Upper Limit:** 1.51 - **Value:** 1.06 **Title:** #### Outcome Measure 103 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.04 - **Spread:** - **Upper Limit:** 0.07 - **Value:** 0.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.03 - **Spread:** - **Upper Limit:** 0.06 - **Value:** 0.04 **Title:** #### Outcome Measure 104 #### Outcome Measure 105 #### Outcome Measure 106 #### Outcome Measure 107 #### Outcome Measure 108 #### Outcome Measure 109 #### Outcome Measure 110 #### Outcome Measure 111 #### Outcome Measure 112 #### Outcome Measure 113 #### Outcome Measure 114 #### Outcome Measure 115 #### Outcome Measure 116 #### Outcome Measure 117 #### Outcome Measure 118 #### Outcome Measure 119 #### Outcome Measure 120 #### Outcome Measure 121 #### Outcome Measure 122 #### Outcome Measure 123 #### Outcome Measure 124 #### Outcome Measure 125 #### Outcome Measure 126 #### Outcome Measure 127 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population consisted of all randomized participants who were exposed to study intervention. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part A: Number of Participants With All Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 2 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion-related reactions (IRR) including hypersensitivity, events related to antibody-dependent enhancement, and events related to immunogenicity. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 3 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 4 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 5 **Description:** AUC of SARS-CoV-2 viral load was measured by Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from Day 1 to Day 8 in nasopharyngeal (NP) swab samples. Analysis was performed using an Analysis of covariance (ANCOVA) model with covariates of treatment and Baseline logarithm (base 10) viral load. **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Viral Pharmacodynamic Population consisted of all participants in the Safety Population who had a Baseline (Day 1) quantifiable viral load as assessed using qRT-PCR from NP swabs. Only those participants with data available at the specified time points without missing covariate information were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 8 **Title:** Part B: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 (AUCD1-8) **Type:** PRIMARY **Unit of Measure:** Day*log10 copies per (/) milliliter (mL) ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 6 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in NP swab samples. Analysis was performed using an ANCOVA model with covariates of treatment, and Baseline logarithm (base10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points without missing covariate information were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 8 **Title:** Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8) **Type:** PRIMARY **Unit of Measure:** Day*log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 7 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events which were not Serious were considered as Non-Serious adverse events. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 12 **Title:** Part A: Number of Participants With Non-Serious AEs Through Week 12 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 8 **Description:** A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part A: Number of Participants With SAEs Through Week 24 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 9 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs are infusion-related reactions (IRR) including hypersensitivity, events related to antibody-dependent enhancement, and events related to immunogenicity. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part A: Number of Participants With AESI Through Week 24 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 10 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Days 1, 5, 11 and 85 (Week 12) **Title:** Part A: Number of Participants With Abnormal ECG Findings at Indicated Time Points **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 11 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Week 24 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 12 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. Adverse events include both Serious and Other Adverse Events. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part B: Number of Participants With All AEs and SAEs Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 13 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion/injection-related reactions (IRR) including hypersensitivity; injection site reactions (ISRs); events related to antibody-dependent enhancement; events related to immunogenicity. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part B: Number of Participants With AESI Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 14 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 15 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 16 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. Adverse events include both Serious and Other Adverse Events. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part C: Number of Participants With All AEs and SAEs Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 17 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part C: Number of Participants With AESI Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 18 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 19 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Day 29 **Title:** Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 20 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 12 **Title:** Part B: Number of Participants With Non-Serious AEs Through Week 12 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 21 **Description:** A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 36 **Title:** Part B: Number of Participants With SAEs Through Week 36 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 22 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs are infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** up to Week 36 **Title:** Part B: Number of Participants With AESI Through Week 36 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 23 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Days 1, 5, 11 and 85 (Week 12) **Title:** Part B: Number of Participants With Abnormal ECG Findings at Indicated Time Points **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 24 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 36 **Title:** Part B: Number of Participants With Disease Progression Events Through Week 36 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 25 **Description:** An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 12 **Title:** Part C: Number of Participants With Non-Serious AEs Through Week 12 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 26 **Description:** A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 36 **Title:** Part C: Number of Participants With SAEs Through Week 36 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 27 **Description:** An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs are infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 36 **Title:** Part C: Number of Participants With AESI Through Week 36 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 28 **Description:** Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Days 1, 5, 11 and 85 (Week 12) **Title:** Part C: Number of Participants With Abnormal ECG Findings at Indicated Time Points **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 29 **Description:** AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population. **Reporting Status:** POSTED **Time Frame:** Up to Week 36 **Title:** Part C: Number of Participants With Disease Progression Events Through Week 36 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 30 **Description:** SARS-CoV-2 viral load was based on saliva and nasal mid-turbinate swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the NEG and \<2.08 results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Virology Population consisted of all participants in the Safety Population with a central lab confirmed quantifiable nasal mid-turbinate and/or saliva swab at Baseline. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline, Days 2, 5, 8, 11, 15, 22 and 29 **Title:** Part A: Change From Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load **Type:** SECONDARY **Unit of Measure:** Log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 31 **Description:** Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the "NEG" and "\<2.08" results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Viral Pharmacodynamic Population consisted of all participants in the Safety Population who had a Baseline (Day 1) quantifiable viral load as assessed using qRT-PCR from NP swabs. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29 **Title:** Part B: Change From Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples **Type:** SECONDARY **Unit of Measure:** Log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 32 **Description:** Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the "NEG" and "\<2.08" results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29 **Title:** Part C: Change From Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples **Type:** SECONDARY **Unit of Measure:** Log10 copies per milliliter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 33 **Description:** Viral load was measured by qRT-PCR from nasopharyngeal swab samples. Viral load (log10 copies/mL) values recorded as negative were considered as undetectable viral load. Percentage of participants with undetectable viral load have been presented. Percentage values are rounded off. **Parameter Type:** NUMBER **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). **Reporting Status:** POSTED **Time Frame:** Days 2, 3, 5, 8, 11, 15, 22 and 29 **Title:** Part B: Percentage of Participants With Undetectable Viral Load **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 34 **Description:** Viral load was measured by qRT-PCR from nasopharyngeal swab samples. Viral load (log10 copies/mL) values recorded as negative were considered as undetectable viral load. Percentage of participants with undetectable viral load have been presented. Percentage values are rounded off. **Parameter Type:** NUMBER **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). **Reporting Status:** POSTED **Time Frame:** Days 2, 3, 5, 8, 11, 15, 22 and 29 **Title:** Part C: Percentage of Participants With Undetectable Viral Load **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 35 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 5. Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points without missing covariate information were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 5 **Title:** Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) **Type:** SECONDARY **Unit of Measure:** Day*log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 36 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 11. Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points without missing covariate information were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 11 **Title:** Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) **Type:** SECONDARY **Unit of Measure:** Day*log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 37 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 5. Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points without missing covariate information were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 5 **Title:** Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) **Type:** SECONDARY **Unit of Measure:** Day*log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 38 **Description:** AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 11. Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points without missing covariate information were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 11 **Title:** Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) **Type:** SECONDARY **Unit of Measure:** Day*log10 copies/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 39 **Description:** Percentage of participants with a persistently high viral load were categorized as \>=4.1 log10 copies/mL and \<4.1 log10 copies/mL. Percentage of participants with a persistently high viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage of participants with a persistently high viral load at Day 8 has been presented. Percentage values are rounded off. **Parameter Type:** NUMBER **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 8 **Title:** Part B: Percentage of Participants With a Persistently High Viral Load at Day 8 **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 40 **Description:** Percentage of participants with a persistently high viral load were categorized as \>=4.1 log10 copies/mL and \<4.1 log10 copies/mL. Percentage of participants with a persistently high viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage of participants with a persistently high viral load at Day 8 has been presented. Percentage values are rounded off. **Parameter Type:** NUMBER **Population Description:** Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 8 **Title:** Part C: Percentage of Participants With a Persistently High Viral Load at Day 8 **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 41 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 42 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Cmax of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 43 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Cmax of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 44 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Cmax of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 45 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Cmax of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 46 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Concentration at Last Quantifiable Time-point (Clast) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 47 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Clast of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 48 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Clast of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 49 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Clast of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 50 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Clast of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Microgram per mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 51 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Time to Reach Cmax (Tmax) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 52 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Tmax of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 53 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Tmax of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 54 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Tmax of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 55 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Tmax of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 56 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. The time frame is beyond Day 169 as there was one PK sample collected outside of the protocol defined window of +/- 7 days that was included in the analysis (PK sample collected up to Day 169 +/- 12 days). **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 57 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. The upper value of the full range is outside of the time frame due to the protocol defined time point of Day 169+/-7 days. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Tlast of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 58 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. The upper value of the full range is outside of the time frame due to the protocol defined time point of Day 169+/-7 days. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Tlast of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 59 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. The time frame is beyond Day 169 as there were a few PK samples collected outside of the protocol defined window of +/- 7 days that were included in the analysis (PK samples collected up to Day 169 +/- 18 days). **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Tlast of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 60 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. The time frame is beyond Day 169 as there were a few PK samples collected outside of the protocol defined window of +/- 7 days that were included in the analysis (PK samples collected up to Day 169 +/- 18 days). **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Tlast of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 61 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29 **Title:** Part A: AUC From Day 1 to 29 (AUCD1-29) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 62 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Title:** Part B: AUCD1-29 of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 63 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Title:** Part B: AUCD1-29 of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 64 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Title:** Part C: AUCD1-29 of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 65 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Title:** Part C: AUCD1-29 of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 66 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUC[0-inf]) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 67 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: AUC(0-inf) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 68 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: AUC(0-inf) of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 69 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: AUC(0-inf) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 70 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: AUC(0-inf) of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 71 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 72 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: AUClast of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 73 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: AUClast of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 74 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: AUClast of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 75 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: AUClast of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 76 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Percentage of AUC(Infinity) Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Percentage of AUCexp ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 77 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: %AUCexp of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Percentage of AUCexp ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 78 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: %AUCexp of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Percentage of AUCexp ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 79 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: %AUCexp of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Percentage of AUCexp ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 80 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: %AUCexp of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Percentage of AUCexp ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 81 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 82 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: t1/2 of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 83 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: t1/2 of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 84 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: t1/2 of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 85 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: t1/2 of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 86 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Apparent Volume of Distribution During the Elimination Phase Following Intravascular Administrtion (Vz) of VIR-7831 **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 87 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Vz of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 88 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Apparent Volume of Distribution During the Elimination Phase Following Extravascular Administration (Vz/F) of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 89 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Vz of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 90 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Vz/F of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 91 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 92 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Vss of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 93 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: Vss of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Liter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 94 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) **Title:** Part A: Clearance (CL) of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Milliliter per day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 95 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: CL of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Milliliter per day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 96 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) **Title:** Part B: Apparent Clearance (CL/F) of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Milliliter per day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 97 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: CL of VIR-7831 After IV Administration **Type:** SECONDARY **Unit of Measure:** Milliliter per day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 98 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Part C: CL/F of VIR-7831 After IM Administration **Type:** SECONDARY **Unit of Measure:** Milliliter per day ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 99 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Dose-normalized least square geometric mean ratio of AUCinf was derived based on collected assessments up to 169 (+/-7 days) for Part B- Sotrovimab Gen2: 500 mg IV arm, and up to 169 (+/-18 days) for Part C- Sotrovimab Gen2: 500 mg IV arm. **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. Data from Parts B and C is presented in a single outcome to determine the absolute bioavailability (F) based on the loge transformed dose normalized AUCinf for the IV (500 mg), IM (500 mg), and IM (250 mg). Data for 500 mg IV arms with similar dosing strategies across Parts B and C is combined as pre-specified in reporting and analysis plan. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Dose-normalized Least Square Geometric Mean Ratio of AUCinf for VIR-7831 Gen2 Between the Three Dose Levels (250 mg IM in Part C, 500 mg IM in Part B and 500 mg IV in Parts B and C) **Type:** SECONDARY **Unit of Measure:** Day*microgram/mL ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Parts B and C. **ID:** OG002 **Title:** Sotrovimab Gen2: 500 mg IV (Parts B and C) #### Outcome Measure 100 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Dose-normalized Least Square Geometric Mean Ratio of AUCinf for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Type:** SECONDARY **Unit of Measure:** Day*microgram per milliliter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 101 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Dose-normalized Least Square Geometric Mean Ratio of AUClast for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Type:** SECONDARY **Unit of Measure:** Day*microgram per milliliter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 102 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic Population. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) **Title:** Dose-normalized Least Square Geometric Mean Ratio of AUCD1-D29 for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Type:** SECONDARY **Unit of Measure:** Day*microgram per milliliter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 103 **Description:** Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). **Dispersion Type:** 90% Confidence Interval **Parameter Type:** GEOMETRIC_LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) **Title:** Dose-normalized Least Square Geometric Mean Ratio of Cmax for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) **Type:** SECONDARY **Unit of Measure:** Microgram per milliliter ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IM ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 104 **Description:** Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Day 28 **Title:** Part A: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 105 **Description:** Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Day 28 **Title:** Part B: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 106 **Description:** Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Day 28 **Title:** Part C: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 107 **Description:** Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Day 28 **Title:** Part A: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 108 **Description:** Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Day 28 **Title:** Part B: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 109 **Description:** Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Day 28 **Title:** Part C: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 110 **Description:** Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part A: Number of Participants With the Presence of Anti-VIR-7831 Antibody **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 111 **Description:** Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part B: Number of Participants With the Presence of Anti-VIR-7831 Antibody **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 112 **Description:** Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part C: Number of Participants With the Presence of Anti-VIR-7831 Antibody **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 113 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibody using a validated electrochemiluminescent (ECL) immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part A: Titers of Anti-drug Antibody to VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 114 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibody using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part B: Titers of Anti-drug Antibody to VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 115 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibody using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Up to Week 24 **Title:** Part C: Titers of Anti-drug Antibody to VIR-7831 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 116 **Description:** Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1) **Title:** Part A: Number of Participants With the Presence of Anti-nucleocapsid (Anti-N), Anti-spike (Anti-S) and Anti-Receptor Binding Domain (Anti-RBD) SARS-CoV-2 Antibodies at Baseline **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 117 **Description:** Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1) **Title:** Part B: Number of Participants With the Presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 118 **Description:** Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1) **Title:** Part C: Number of Participants With the Presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 119 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1) **Title:** Part A: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 120 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1) **Title:** Part B: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 121 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1) **Title:** Part C: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 122 **Description:** Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Part A: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 123 **Description:** Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Part B: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 124 **Description:** Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Part C: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Outcome Measure 125 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Part A: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** OG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** OG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Outcome Measure 126 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Part B: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** OG000 **Title:** Part B- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** OG001 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Outcome Measure 127 **Description:** Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted. **Population Description:** Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Part C: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29 **Type:** OTHER_PRE_SPECIFIED ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** OG000 **Title:** Part C- Sotrovimab Gen2: 500 mg IV ##### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** OG001 **Title:** Part C- Sotrovimab Gen2: 250 mg IM ### Participant Flow Module #### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A. **ID:** FG000 **Title:** Part A-Sotrovimab Gen1: 500 mg IV #### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A. **ID:** FG001 **Title:** Part A- Sotrovimab Gen2: 500 mg IV #### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B. **ID:** FG002 **Title:** Part B- Sotrovimab Gen2: 500 mg IV #### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B. **ID:** FG003 **Title:** Part B- Sotrovimab Gen2: 500 mg IM #### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C. **ID:** FG004 **Title:** Part C- Sotrovimab Gen2: 500 mg IV #### Group **Description:** Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C. **ID:** FG005 **Title:** Part C- Sotrovimab Gen2: 250 mg IM #### Period **Title:** Part A: Up to Week 24 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** Treatment Received ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 #### Period **Title:** Part B: Up to Week 36 ##### Withdraw **Type:** Randomized, but did not receive treatment ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 84 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 83 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** Treatment Received ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 84 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 82 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 84 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 81 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 #### Period **Title:** Part C: Up to Week 36 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 1 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 4 ###### Reason **Group ID:** FG005 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 79 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 78 ##### Milestone **Type:** Treatment Received ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 79 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 78 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 75 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 75 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 3 **Pre-Assignment Details:** Total of 354 participants (30 participants in Part A, 167 participants in Part B, 157 participants in Part C) were enrolled in the study. **Recruitment Details:** Randomized, parallel group study conducted in non-hospitalized participants with mild to moderate Coronavirus Disease 2019 (COVID-19) who received Sotrovimab (VIR-7831) Generation1 (Gen 1) and Gen2. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04547179 **Brief Title:** Medicinal vs. Orthotic Comparison for Migraine Prevention: A Double-Blind Study **Official Title:** Medicinal vs. Orthotic Comparison for Migraine Prevention: A Double-Blind Study #### Organization Study ID Info **ID:** 0001 #### Organization **Class:** OTHER **Full Name:** Manhattan Beach Orthodontics ### Status Module #### Completion Date **Date:** 2021-12-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2021-01-22 **Type:** ACTUAL **Last Update Submit Date:** 2021-01-18 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-04-15 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-01 **Type:** ESTIMATED **Status Verified Date:** 2021-01 #### Study First Post Date **Date:** 2020-09-14 **Type:** ACTUAL **Study First Submit Date:** 2020-09-07 **Study First Submit QC Date:** 2020-09-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Manhattan Beach Orthodontics #### Responsible Party **Investigator Affiliation:** Manhattan Beach Orthodontics **Investigator Full Name:** Dr. Sunitha Bharadia **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** To understand the impacts of using a fixed orthotic facial exercise appliance (BLAfit®) for migraine reduction, as compared to medication (fremanezumab-vfrm) and control. **Detailed Description:** The investigators will be studying the impacts of using an orthotic facial exercise device (BLAfit®) in the prevention of migraines for those who suffer from roughly 10-15 migraines per month. In order to test the efficacy of this device and its exercise routine, investigators will have one arm of our study receive the BLAfit® device and perform the exercises for one minute daily for three months. In Arm #2, there will be another treatment: Ajovy® (fremanezumab-vfrm) injections- which is a known and commonly practiced clinical prevention treatment for migraine patients. Patients in this arm will receive three injections of Ajovy, which is will be meant to last 3 months. In addition, investigators will have a placebo group that will receive three saline injections, which are meant to mimic the three Ajovy® injections. Arms #2 and #3 of this study will be conducted in a double-blind fashion, as both the clinician providing the injections and the patients receiving the injections will not know if the injecting substance is Ajovy or saline, so as to minimize bias. All patients in all three months will log their number and pain level of their migraines each day for three months. Upon conclusion, they will meet with our in-house neurologist (Principal Investigator \& Sponsor) for a final in-person evaluation and questionnaire. Results from the three groups will then be analyzed. ### Conditions Module **Conditions:** - Migraine **Keywords:** - Migraine - Ajovy - facial exercise - fremanezumab-vfrm ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 80 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In this arm, subjects will used the fixed orthotic device called BLAfit® for one minute of facial exercise a day for three months. **Intervention Names:** - Device: BLAfit® **Label:** BLAfit® usage **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects in this arm will receive three Ajovy® (fremanezumab-vfrm) injections at the start of month 2. This will be conducted in a double-blind fashion, as both the clinician providing the injection, and the subject, will not know if the injection is actually Ajovy® or just saline. **Intervention Names:** - Drug: Fremanezumab-Vfrm **Label:** fremanezumab-vfrm **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** This is a placebo that is used to counter Arm #2- the Ajovy® injections. Subjects in this arm will receive three saline injections at the start of month 2 that will mimic the Ajovy® injections. This will be conducted in a double-blind fashion, as both the clinician providing the injection, and the subject, will not know if the injection is actually Ajovy® or just saline. **Intervention Names:** - Other: Saline **Label:** Saline injection **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - fremanezumab-vfrm **Description:** Patients will receive three injections of Ajovy® if in the corresponding arm of the study. **Name:** Fremanezumab-Vfrm **Other Names:** - Ajovy® **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - BLAfit® usage **Description:** Usage of the BLAfit device, a fixed orthotic appliance that allows users to tone facial muscles with one minute usage per day **Name:** BLAfit® **Other Names:** - Bella Lip Appliance® - BLA® **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Saline injection **Description:** Patients will receive three injections of saline if in the corresponding arm of the study. This is a placebo meant to simulate the Ajovy® injection. **Name:** Saline **Other Names:** - salt and water solution **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The frequency and pain level of subjects' migraines will be assessed upon the conclusion of the study through surveying and comparing to previous survey data. **Measure:** Frequency and Pain Level of Migraines Post-Treatment **Time Frame:** 4 months after start ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Those eligible to participate must be between the ages of 18 to 55 years. * The individual must experience at least 2 migraines per week. * They must be capable of visiting the medical facility in Manhattan Beach, California where the in-person screening and final evaluation will be conducted (following COVID-19 public health guidelines). * They must be able to communicate with the study team via any teleconferencing service such as Zoom, Google Hangouts, or FaceTime. Exclusion Criteria: * Patients must not have any intracranial pathology, neurological or psychological conditions, epilepsy, cancer, any history of chemotherapy, hospitalized for depression, psychiatric conditions, seizures, or tumors. * Patients cannot have taken Botox® for migraine treatments. * Patients cannot have had a history of head or neck surgery. * Patients cannot be taking: propranolol, amitriptyline, flunarizine, topiramate, combination, galcanezumab-gnlm, fremanezumab-vfrm, or erenumab-aooe. * Patients must not be deemed a vulnerable subject (including but not limited to: children, prisoners, pregnant women, mentally disabled persons). **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** drmaryamb@aol.com **Name:** Maryam Bakhtiyari, DDS **Phone:** 3103726600 **Role:** CONTACT **Contact 2:** **Email:** sbbrainmd@yahoo.com **Name:** Sunitha Bharadia, MD **Phone:** (310) 370-4700 **Role:** CONTACT #### Locations **Location 1:** **City:** Manhattan Beach **Contacts:** ***Contact 1:*** - **Name:** Maryam Bakhtiyari, DDS - **Phone:** 310-372-6600 - **Role:** CONTACT **Country:** United States **Facility:** Manhattan Beach Orthodontics **State:** California **Zip:** 90266 #### Overall Officials **Official 1:** **Affiliation:** Manhattan Beach Orthodontics **Name:** Sunitha Bharadia, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000051270 - Term: Headache Disorders, Primary - ID: D000020773 - Term: Headache Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M11852 - Name: Migraine Disorders - Relevance: HIGH - As Found: Migraine - ID: M21089 - Name: Facies - Relevance: LOW - As Found: Unknown - ID: M9351 - Name: Headache - Relevance: LOW - As Found: Unknown - ID: M22529 - Name: Headache Disorders - Relevance: LOW - As Found: Unknown - ID: M26657 - Name: Headache Disorders, Primary - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008881 - Term: Migraine Disorders ### Intervention Browse Module - Ancestors - ID: D000077221 - Term: Calcitonin Gene-Related Peptide Receptor Antagonists - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: VaDiAg - Name: Vasodilator Agents ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M269877 - Name: Erenumab - Relevance: HIGH - As Found: Extra-hepatic - ID: M5379 - Name: Calcitonin - Relevance: LOW - As Found: Unknown - ID: M260622 - Name: Salmon calcitonin - Relevance: LOW - As Found: Unknown - ID: M18305 - Name: Calcitonin Gene-Related Peptide - Relevance: LOW - As Found: Unknown - ID: M254422 - Name: Katacalcin - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000605816 - Term: Erenumab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05279079 **Acronym:** MAP-1 **Brief Title:** Markers in Acute Pancreatitis-1 **Official Title:** International Prospective Evaluation of Novel Biomarkers to Detect and Predict the Severity of Drug- Associated Acute Pancreatitis in Adults #### Organization Study ID Info **ID:** UoL001572 #### Organization **Class:** OTHER **Full Name:** University of Liverpool ### Status Module #### Completion Date **Date:** 2024-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-03-15 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-03 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-03 **Type:** ESTIMATED **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2022-03-15 **Type:** ACTUAL **Study First Submit Date:** 2022-02-18 **Study First Submit QC Date:** 2022-03-03 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Innovative Medicines Initiative **Class:** UNKNOWN **Name:** TransBioLine Consortium **Class:** OTHER_GOV **Name:** Liverpool University Hospitals NHS Foundation Trust **Class:** UNKNOWN **Name:** Klinikum der Universität München **Class:** OTHER **Name:** Hospital Regional de Malaga #### Lead Sponsor **Class:** OTHER **Name:** University of Liverpool #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Prospective, multi-national, multi-centre observational diagnostic study of novel microRNA and protein biomarkers in peripheral blood and/or urine to detect and predict the severity of drug-associated acute pancreatitis (AP), with comparison of the same biomarkers in patients with acute pancreatitis from other causes, chronic pancreatitis, pancreatic cancer, diabetes mellitus and healthy volunteers. **Detailed Description:** The MAP-1 study is designed to validate microRNA and/or pancreatic digestive enzyme biomarkers for the detection and severity assessment of drug-associated AP, for application to the assessment of adverse reactions to drugs in development or drugs already developed for other indications. The study will also assess the clinical utility of these biomarkers in AP from other causes, but is not designed to determine whether the biomarkers could be used in place of amylase and/or lipase in the standard clinical diagnosis of AP or to distinguish between the many differential diagnoses of AP. Selection is in progress of the microRNAs and pancreatic digestive enzyme biomarkers to be validated in this study, this selection being made from prospectively biobank samples obtained in a separate observational study that has separate ethical approval. The pre-selected microRNAs and pancreatic digestive enzymes will be measured in the blood and urine of patients on admission to hospital with drug-associated acute pancreatitis (Group 1, 75 participants in receipt of one or more drugs on a defined list of drugs associated with acute pancreatitis) or other cause acute pancreatitis (Group 2, 250 participants not in receipt of any of the defined drugs). The same biomarkers will also be measured in blood and urine samples from contrast groups of patients with chronic pancreatitis (Group 3, 25 participants), pancreas cancer (Group 4, 25 participants), type I or II diabetes mellitus (Group 5, 25 participants) and healthy volunteers (Group 6, 100 participants). All participants will be at least 18 years old. MicroRNAs will be measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and pancreatic enzymes by mass spectrometry. ### Conditions Module **Conditions:** - Acute Pancreatitis Drug-Induced ### Design Module #### Bio Spec **Description:** Blood samples (10 ml in ethylene diamine tetra-acetic acid, EDTA, 8.5 ml in serum separator tube, SST, 2.5 ml in RNA PAXgene) and urine samples (50 ml collected in Falcon or other tube) will be taken at a single sampling time point from individuals in all groups. These samples will be taken on hospital admission from recruited patients in Groups 1 and 2. Further blood samples (10 ml in EDTA, 8.5 ml in SST and 2.5 ml in RNA PAXgene) will be taken at Day 4 (+/- 1 day) and Day 14 (+/- 2 days) from participants in Groups 1 and 2 from within the United Kingdom. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** OTHER **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 500 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Drug-associated AP: patients aged 18 or more years undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP **Intervention Names:** - Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Label:** Group 1 #### Arm Group 2 **Description:** Other cause AP: patients aged 18 or more years not undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP **Intervention Names:** - Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Label:** Group 2 #### Arm Group 3 **Description:** Chronic pancreatitis: patients aged 18 or more years with symptomatic chronic pancreatitis confirmed by CT or MRI **Intervention Names:** - Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Label:** Group 3 #### Arm Group 4 **Description:** Pancreas cancer: patients aged 18 or more years with biopsy proven pancreas cancer **Intervention Names:** - Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Label:** Group 4 #### Arm Group 5 **Description:** Diabetes mellitus: patients aged 18 or more years with type 1 or type 2 diabetes mellitus in receipt of insulin or oral hypoglycaemics **Intervention Names:** - Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Label:** Group 5 #### Arm Group 6 **Description:** Healthy volunteers **Intervention Names:** - Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Label:** Group 6 ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1 - Group 2 - Group 3 - Group 4 - Group 5 - Group 6 **Description:** Panel of microRNA and pancreatic enzyme biomarkers **Name:** Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Scale of change from normal (healthy volunteer values) of a panel of microRNAs measured in blood and urine samples from patients with mild, moderate or severe drug-associated AP during the first 24 hours of admission, confirming specificity by comparison with results from patients with other pancreatic diseases **Measure:** MicroRNA panel **Time Frame:** Day of admission #### Secondary Outcomes **Description:** Scale of change from normal (healthy volunteer values) of a selected pancreatic enzyme biomarker in blood and/or urine taken from patients with mild, moderate or severe drug-associated AP during the first 24 hours of admission, confirming specificity by comparison with results from patients with other pancreatic diseases **Measure:** Pancreatic enzyme biomarker **Time Frame:** Day of admission **Description:** Scale of change of circulating microRNAs measured in blood samples on Day 4 (+/- 1 day) and Day 14 (+/- 2 days) after admission to assess progression of AP **Measure:** MicroRNA panel **Time Frame:** Days 4 and 14 after admission **Description:** Determination of AP severity will be made according to the Revised Atlanta Classification **Measure:** Severity of AP **Time Frame:** Within 90 days of admission **Description:** Application of the PAtieNt-rePoRted OutcoMe scale in acute pancreatItis - an international proSpEctive cohort study (PAN-PROMISE) scale **Measure:** Patient reported outcome **Time Frame:** Days 4 and 14 **Description:** Progress of recruitment of patients into MAP-1 **Measure:** Progress of MAP-1 **Time Frame:** Two years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Drug-associated AP: patients ≥18 years old undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP and admitted to recruiting hospitals with a diagnosis of AP established by two of: (i) typical continuous upper abdominal pain (in this study for up to 2 days in duration prior to admission); (ii) amylase and/or lipase 3 or more times the upper limit of normal; (iii) characteristic findings on abdominal imaging (if undertaken urgently by computerised tomography scan (CT) or magnetic resonance imaging (MRI); and who undergo their first study blood sampling within 24 hours of admission to hospital. 2. Other cause AP: patients ≥18 years old not undergoing drug treatment that has a defined risk of AP and admitted to recruiting hospitals with a diagnosis of AP established by two of: (i) typical continuous upper abdominal pain (in this study for up to 2 days in duration prior to admission); (ii) amylase and/or lipase 3 or more times the upper limit of normal; (iii) characteristic findings on abdominal imaging (if undertaken urgently by CT or MRI) and undergo their first study blood sampling within 24 hours of hospital admission. 3. Chronic pancreatitis: patients with symptomatic chronic pancreatitis and diagnostic abnormalities identified by CT and/or MRI and who undergo study blood sampling as an outpatient. 4. Pancreatic cancer: patients presenting with biopsy-proven or presumed pancreatic cancer and who undergo study blood sampling as an outpatient; in patients with a presumptive diagnosis of pancreatic cancer, blood and urine samples will be analysed after histological confirmation. 5. Diabetes mellitus: adult patients with type 1 or type 2 diabetes mellitus treated with insulin and/or oral anti-hyperglycaemic medication for at least 3 months and ongoing and who undergo study blood sampling as an outpatient. 6. Healthy volunteers: normal, healthy individuals aged ≥18 years old without evidence of systemic disease who have required no hospital intervention within the last year and received no drug treatment within the last 3 months and are severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) negative. Exclusion Criteria: 1. Drug-associated AP: onset of continuous abdominal pain more than 2 days prior to admission to hospital; known previous AP within the last 3 months; known chronic pancreatitis; known pancreatic or hepatobiliary malignancy; previous necrosectomy or pancreatic surgery; known prior type 1 or type 2 diabetes mellitus. Patients will not be excluded if they are undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP and an alternative cause for AP is identified (including after recruitment and blood sampling). 2. Other cause AP: undergoing drug treatment that has a defined risk of AP (such patients should be considered for recruitment into Group 2); onset of continuous abdominal pain more than 2 days prior to admission to hospital; known previous AP within the last 3 months; known chronic pancreatitis; known pancreatic or hepatobiliary malignancy; previous necrosectomy or pancreatic surgery; type 1 or type 2 diabetes mellitus. 3. Chronic pancreatitis: hospital admission with AP within the last three months; known pancreatic or hepatobiliary malignancy; previous necrosectomy or pancreatic surgery; type 1 or type 2 diabetes mellitus. 4. Pancreatic cancer: hospital admission with AP within the last 3 months; known chronic pancreatitis; previous necrosectomy or pancreatic surgery and/or chemotherapy prior to sampling; type 1 or type 2 diabetes mellitus. 5. Diabetes mellitus: hospital admission with AP within the last 3 months; known type 3c diabetes mellitus; known history of acute or chronic pancreatitis; known history of cystic fibrosis, known history of pancreatic or hepatobiliary malignancy; known history of necrosectomy or pancreatic surgery; gestational diabetes mellitus; monogenic diabetes mellitus syndromes; post-transplantation diabetes mellitus; diabetes mellitus attributed to drugs or toxins. 6. Healthy volunteers: abnormal physical examination, abnormal routine haematology, urea, electrolytes and/or liver function tests; evidence of systemic disease; solid or haematological neoplasia within the last 5 years; hospital intervention within last 12 months; scheduled drug treatment within last 3 months and/or as required drug treatment within the last 4 weeks; infection or other sources of acute inflammation within the last 3 months. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adult participants aged 18 years or more, comprised of 6 Groups: Group 1: Drug-associated AP Group 2: Other cause AP Group 3: Chronic pancreatitis Group 4: Pancreas Cancer Group 5: Diabetes mellitus Grouip 6: Healthy volunteers ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** r.sutton@liverpool.ac.uk **Name:** Robert Sutton, MD FRCS PhD **Phone:** +44 (0)151 795 8024 **Role:** CONTACT **Contact 2:** **Email:** latawiec@liverpool.ac.uk **Name:** Diane Latawiec, MSc PGCert **Phone:** +44 (0)151 794 9951 **Role:** CONTACT #### Locations **Location 1:** **City:** Liverpool **Contacts:** ***Contact 1:*** - **Email:** r.sutton@liverpool.ac.uk - **Name:** Robert Sutton, MD FRCS PhD - **Role:** CONTACT ***Contact 2:*** - **Email:** latawiec@liverpool.ac.uk - **Name:** Diane Latawiec, MSc PGCert - **Role:** CONTACT **Country:** United Kingdom **Facility:** Royal Liverpool University Hospital **State:** Merseyside **Zip:** L7 8XP #### Overall Officials **Official 1:** **Affiliation:** University of Liverpool **Name:** Robert Sutton, MD FRCS PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004066 - Term: Digestive System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13115 - Name: Pancreatitis - Relevance: HIGH - As Found: Pancreatitis - ID: M13102 - Name: Pancreatic Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010195 - Term: Pancreatitis ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M22554 - Name: Pancrelipase - Relevance: LOW - As Found: Unknown - ID: M13114 - Name: Pancreatin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03093779 **Acronym:** HIL **Brief Title:** Mechanisms of Health Literacy and Information Accessibility in the Deaf **Official Title:** Mechanisms of Health Literacy and Information Accessibility in the Deaf #### Organization Study ID Info **ID:** HUM00104423 #### Organization **Class:** OTHER **Full Name:** University of Michigan ### Status Module #### Completion Date **Date:** 2021-08-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-10-06 **Type:** ACTUAL **Last Update Submit Date:** 2021-09-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-08-30 **Type:** ACTUAL #### Start Date **Date:** 2016-12-09 **Type:** ACTUAL **Status Verified Date:** 2021-09 #### Study First Post Date **Date:** 2017-03-28 **Type:** ACTUAL **Study First Submit Date:** 2017-03-22 **Study First Submit QC Date:** 2017-03-22 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Rochester Institute of Technology **Class:** OTHER **Name:** Sinai Health System **Class:** OTHER **Name:** Hurley Medical Center **Class:** OTHER **Name:** Boston University #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** Michael McKee **Investigator Title:** Assistant Professor of Family Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this proposal is to examine the attitudes, knowledge, and skills related to health information that influence health literacy among Deaf individuals.The study team will also examine frequently overlooked potential predictors of health literacy, including cognitive abilities, resilience, and self-efficacy. To achieve the study objectives, researchers will conduct an explanatory sequential mixed methods design using extensive quantitative data collection procedures, namely, cross-sectional surveys and measures that will identify predictors and moderators of health literacy with Deaf and hearing subjects. These results will inform the subsequent qualitative assessment using elicitation interviews that will help explain the quantitative results, and elucidate how and why Deaf individuals access and understand health information. A community advisory board consisting of Deaf community members will provide oversight to the proposal that will be led by multiple Deaf investigators, including the PI. The Deaf community, due to communication barriers, relative social marginalization, and their reliance on visual learning, provides a unique insight into how health information is distributed and disseminated visually. Findings may be applicable to other individuals with hearing loss who navigate and cope with life more visually than the typical hearing person. This will be critical to determine more accurately the effect of visual learning and existing online health information on health literacy. **Detailed Description:** University of Michigan(UM) is the clinical coordinating center (CCC) and data coordinating center (DCC) for this study. There are no subject recruitment or interaction will take place at UM. CCC engages clinicians and the clinical research mission and provides the training and professional development to ensure effective study by recruiting and maintaining the study sites performed at the Hurley Medical Center at Flint, Michigan, The National Technical Institute of Technology(NTID) at Rochester Institute of Technology in Rochester, New York, and The Sinai Deaf Health(SDH)program in Chicago, Illinois including participates. Thus, educating and training investigators, study coordinators, and other research staff to ensure an ongoing quality improvement of research processes. DCC is highly invested in producing the highest quality survey questionnaires for use with deaf ASL-users and hearing, English speakers. The study team will only use the best possible ASL translations of the data collection measures in order to best obtain accurate, high-quality research. University of Michigan (UM) will function as the lead site, not as a performance site. UM will oversee all three other sites and conduct quality checks with each site, assist with training of the staff for standardization, and conduct data management/storage of de-identified data along with analysis. Hard copies and identifiers will be maintained at each site as per their approved IRB protocols. The two primary objectives of this proposal are: * To elucidate the role of information marginalization on health literacy in Deaf American Sign Language (ASL) users * To better understand the mechanisms of health literacy in this population so as to identify viable targets for future health literacy intervention development. This proposal is responsive to PAR-10-133's request for studies that assess mechanisms underlying health literacy, including roles of cognition, culture, language fluency, and information-seeking and interpretation ability in the deaf population and, how these may differ from the hearing population. A secondary objective is to assess how varying levels of hearing loss can affect individuals' abilities to access and comprehend health information and their health literacy adequacy. ### Conditions Module **Conditions:** - Hearing Loss - Health Literacy **Keywords:** - Hearing Loss - Deaf - Health Literacy - Health Information - Visual Learning ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 901 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individuals who are deaf and use sign language to communicate. **Intervention Names:** - Other: Health Information Assessment **Label:** Deaf #### Arm Group 2 **Description:** Individuals with no hearing loss and who communicate in spoken English. **Intervention Names:** - Other: Health Information Assessment **Label:** Hearing ### Interventions #### Intervention 1 **Arm Group Labels:** - Deaf - Hearing **Description:** Assess how hearing loss and health literacy alters the ability to access and comprehend online health information **Name:** Health Information Assessment **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Use of the American Sign Language- Newest Vital Sign and the English version of the Newest Vital Sign will be used to assess health literacy. Scores range from 0-6 with 5-6 considered to be adequate health literacy. **Measure:** Health Literacy **Time Frame:** 5 minutes in a single data assessment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Deaf American Sign Language Users: - deaf persons who use sign language and live in Flint, Michigan, Rochester NY, and Chicago, IL metropolitan areas. Hearing, English speakers: - hearing persons who speak fluent English and live in Flint, Michigan, Rochester NY, and Chicago, IL metropolitan areas. Exclusion Criteria: * Those who have cognitive impairment (e.g., due to dementia, delirium or intoxication). * Those who unable to consent to the study. * Individuals with limited vision will be excluded if they are unable to effectively use a PC (i.e., function vision at 20-200 or worse). **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** 450 Deaf ASL users and 450 Hearing native English speakers ### Contacts Locations Module #### Locations **Location 1:** **City:** Chicago **Country:** United States **Facility:** Mount Sinai Hospital **State:** Illinois **Zip:** 60608 **Location 2:** **City:** Flint **Country:** United States **Facility:** Hurley Medical Center **State:** Michigan **Zip:** 48503 **Location 3:** **City:** Rochester **Country:** United States **Facility:** Rochester Institute of Technology/National Technical Institute for the Deaf **State:** New York **Zip:** 14623 #### Overall Officials **Official 1:** **Affiliation:** University of Michigan **Name:** Michael McKee, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** McKee MM, Hauser PC, Champlin S, Paasche-Orlow M, Wyse K, Cuculick J, Buis LR, Plegue M, Sen A, Fetters MD. Deaf Adults' Health Literacy and Access to Health Information: Protocol for a Multicenter Mixed Methods Study. JMIR Res Protoc. 2019 Oct 9;8(10):e14889. doi: 10.2196/14889. **PMID:** 31599730 **Citation:** Champlin S, Cuculick J, Hauser PC, Wyse K, McKee MM. Using Gaze Tracking as a Research Tool in the Deaf Health Literacy and Access to Health Information Project: Protocol for a Multisite Mixed Methods Study and Preliminary Results. JMIR Res Protoc. 2021 Sep 7;10(9):e26708. doi: 10.2196/26708. **PMID:** 34491211 **Citation:** Panko TL, Contreras J, Postl D, Mussallem A, Champlin S, Paasche-Orlow MK, Hill J, Plegue MA, Hauser PC, McKee M. The Deaf Community's Experiences Navigating COVID-19 Pandemic Information. Health Lit Res Pract. 2021 Apr;5(2):e162-e170. doi: 10.3928/24748307-20210503-01. Epub 2021 Jun 22. **PMID:** 34213997 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006311 - Term: Hearing Disorders - ID: D000004427 - Term: Ear Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases - ID: D000012678 - Term: Sensation Disorders - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M24420 - Name: Hearing Loss - Relevance: HIGH - As Found: Hearing Loss - ID: M6840 - Name: Deafness - Relevance: HIGH - As Found: Hearing Loss - ID: M9400 - Name: Hearing Disorders - Relevance: LOW - As Found: Unknown - ID: M7601 - Name: Ear Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - Relevance: LOW - As Found: Unknown - ID: M15490 - Name: Sensation Disorders - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000034381 - Term: Hearing Loss - ID: D000003638 - Term: Deafness ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04158479 **Brief Title:** China Extracorporeal Life Support Registry **Official Title:** China Extracorporeal Life Support Registry #### Organization Study ID Info **ID:** 2019040X #### Organization **Class:** OTHER **Full Name:** Beijing Anzhen Hospital ### Status Module #### Completion Date **Date:** 2030-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-09 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-07 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2030-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2017-01-01 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2019-11-08 **Type:** ACTUAL **Study First Submit Date:** 2019-11-07 **Study First Submit QC Date:** 2019-11-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Beijing Anzhen Hospital #### Responsible Party **Investigator Affiliation:** Beijing Anzhen Hospital **Investigator Full Name:** Xiaotong Hou **Investigator Title:** Chief, Center for Cardiac Intensive Care **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Extracorporeal life support (ECLS), also known as extracorporeal membrane oxygenation (ECMO), is an extracorporeal technique of providing effective cardiac and respiratory support to patients with lungs and/or heart failure. There was a growth in ECLS cases, centers, and center scale in China during the past decade. This multi-center registry was conducted by Chinese Society of Extracorporeal Life Support. The objectives were to investigate China statistics of ECLS and to evaluate the short-term and long-term outcomes of patients with ECLS. **Detailed Description:** Extracorporeal life support (ECLS), also known as extracorporeal membrane oxygenation (ECMO), is an extracorporeal technique of providing effective cardiac and respiratory support to patients with lungs and/or heart failure. There was a growth in ECLS cases, centers, and center scale in China during the past decade. The objectives were to investigate China statistics of ECLS and to evaluate the short-term and long-term outcomes of patients with ECLS. This multi-center registry was conducted by Chinese Society of Extracorporeal Life Support. Data were submitted by the following member institutions: AFFILIATED HOSPITAL OF GUANGDONG MEDICAL UNIVERSITY, AFFILIATED HOSPITAL OF JINING MEDICAL UNIVERSITY, AFFILIATED HOSPITAL OF NANTONE UNIVERSITY, AFFILIATED HOSPITAL OF ZUNYI MEDICAL UNIVERSITY, ANHUI PROVINCIAL HOSPITAL, BEIJING ANZHEN HOSPITAL, CAPITAL MEDICAL UNIVERSITY, BEIJING CHILDREN'S HOSPITAL, CAPITAL MEDICAL UNIVERSITY, BEIJING FRIENDSHIP HOSPITAL, CAPITAL MEDICAL UNIVERSITY, BEIJING CHAO-YANG HOSPITAL, CAPITAL MEDICAL UNIVERSITY, BINZHOU MEDICAL UNIVERSITY HOSPITAL, CHANGHAI HOSPITAL, CHILDREN'S HOSPITAL OF SHANGHAI JIAOTONG UNIVERSITY, CHINESE PLA GENERAL HOSPITAL, DALIAN CENTRAL HOSPITAL, DONGGUAN PEOPLE'S HOSPITAL, FIRST AFFILIATED HOSPITAL OF KUNMING MEDICAL UNIVERSITY, FUJIAN PROVINCIAL HOSPITAL, FUZHOU PULMONARY HOSPITAL OF FUJIAN, GENERAL HOSPITAL OF NINGXIA MEDICAL UNIVERSITY, GUANGDONG PROVINCIAL PEOPLES HOSPITAL, HAINAN GENERAL HOSPITAL, HENAN PROVINCIAL CHEST HOSPITAL, HENAN PROVINCIAL PEOPLES HOSPITAL, NINGBO FIRST HOSPITAL (NINGBO HOSPITAL OF ZHEJIANG UNIVERSITY, PEKING UNION MEDICAL COLLEGE HOSPITAL, PEKING UNIVERSITY PEOPLE'S HOSPITAL, PEKING UNIVERSITY THIRD HOSPITAL, SHANXI PROVINCIAL PEOPLE'S HOSPITAL, SHENGJING HOSPITAL OF CHINAMESICAL UNIVERSITY, SHUNDE HOSPITAL OF SOUTHERN MEDICAL UNIVERSITY, SUZHOU MUNICIPAL HOSPITAL, TAIZHOU HOSPITAL OF ZHEJIANG PROVINCE, THE 2ND AFFILIATED HOSPITAL OF HARBIN MEDICAL UNIVERSITY, THE AFFILIATED HOSPITAL OF HANGZHOU NORMAL UNIVERSITY, THE AFFILIATED HOSPITAL OF QINGDAO UNIVERSITY, THE AFFILIATED HOSPITAL OF XUZHOU MEDICAL UNIVERSITY, THE CHILDREN'S HOSPITAL ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE, THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIVERSITY, THE FIRST AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIVERSITY, THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIVERSITY, THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIVESITY, THE FIRST HOSPITAL AFFILIATED TO AMU (SOUTHWEST HOSPITAL), THE FIRST HOSPITAL OF LANZHOU UNIVERSITY, THE FIRST HOSPITAL OF ZHEJIANG PROVINCE, THE FIRST PEOPLE'S HOSPITAL OF YUEYANG, THE NORTHERN JIANGSU PEOPLES HOSPITAL, THE PEOPLE'S HOSPITAL OF GUANGXI ZHUANG AUTONOMOUS REGION, THE SECOND AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIVERSITY, THE SECOND AFFILIATED HOSPITAL OF ZHENGZHOU UNIVERSITY, THE SECOND AFFILIATED HOSPITAL OF ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE, THE SECOND HOSPITAL OF JILIN UNIVERSITY, THE SECOND XIANGYA HOSPITAL OF CENTRAL SOUTH UNIVERSITY, THE SIXTH MEDICAL CENTER OF PLA GENERAL HOSPITAL, THE THIND AFFILIATED HOSPITAL OF XINJIANG MEDICAL UNIVERSITY, WEST CHINA HOSPITAL，SICHUAN UNIVERSITY, WUHAN ASIA HEART HOSPITAL, WUHAN JINYINTAN HOSPITAL, WUHAN UNION HOSPITAL, XIANGYIA HOSPITAL CENTRAL SOUTH UNIVERSITY, XIJING HOSPITAL, ZHEJIANG PROVINCE PEOPLE'S HOSPITAL, ZHON GNAN HOSPITAL OF WUHAN UNIVERSITY, ZHONGDA HOSPITAL SOUTHEAST UNIVERSITY, ZHONGSHAN HOSPITAL ### Conditions Module **Conditions:** - Cardiogenic Shock - Cardiac Arrest - Heart Failure - Acute Respiratory Distress Syndrome - Acute Respiratory Failure ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 20000 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 1 Year ### Arms Interventions Module #### Arm Group 1 **Description:** ECMO support for acute respiratory failure, ARDS **Intervention Names:** - Device: ECMO **Label:** Pulmonary Support #### Arm Group 2 **Description:** ECMO support for heart failure, cardiogenic shock **Intervention Names:** - Device: ECMO **Label:** Cardiac Support #### Arm Group 3 **Description:** ECMO support for cardia arrest **Intervention Names:** - Device: ECMO **Label:** Extracorporeal Cardiopulmonary Resuscitation ### Interventions #### Intervention 1 **Arm Group Labels:** - Cardiac Support - Extracorporeal Cardiopulmonary Resuscitation - Pulmonary Support **Description:** ECMO for circulatory and/or respiratory support **Name:** ECMO **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** All-cause mortality **Time Frame:** 30 days #### Secondary Outcomes **Measure:** All-cause mortality **Time Frame:** 365 days **Measure:** Rate of successful weaning from ECMO **Time Frame:** 30 days **Description:** Bleeding requiring transfusion or surgery, stroke, sepsis, limb ischemia requiring intervention, system or cannula change **Measure:** ECMO-related complications **Time Frame:** 30 days **Description:** Acute renal failure, ulcer bleeding, pneumonia, sepsis **Measure:** Other complications **Time Frame:** 30 days **Measure:** Duration stay at ICU and hospital **Time Frame:** 365 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients receiving ECMO for circulatory and/or respiratory support Exclusion Criteria: * Refusal of consent **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Patients receiving ECMO for circulatory and/or respiratory support ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** xt.hou@ccmu.edu.cn **Name:** Xiaotong Hou, MD., PhD. **Phone:** 8610 64456631 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** xt.hou@ccmu.edu.cn - **Name:** Xiaotong Hou, MD., PhD. - **Phone:** 8610 64456631 - **Role:** CONTACT ***Contact 2:*** - **Name:** Xiaotong Hou, MD., PhD. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University **State:** Beijing **Status:** RECRUITING **Zip:** 100029 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000012120 - Term: Respiration Disorders - ID: D000007235 - Term: Infant, Premature, Diseases - ID: D000007232 - Term: Infant, Newborn, Diseases - ID: D000055370 - Term: Lung Injury - ID: D000009203 - Term: Myocardial Infarction - ID: D000017202 - Term: Myocardial Ischemia - ID: D000014652 - Term: Vascular Diseases - ID: D000007238 - Term: Infarction - ID: D000007511 - Term: Ischemia - ID: D000010335 - Term: Pathologic Processes - ID: D000009336 - Term: Necrosis - ID: D000012769 - Term: Shock ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14965 - Name: Respiratory Distress Syndrome - Relevance: HIGH - As Found: Respiratory Distress Syndrome - ID: M14964 - Name: Respiratory Distress Syndrome, Newborn - Relevance: HIGH - As Found: Respiratory Distress Syndrome - ID: M14968 - Name: Respiratory Insufficiency - Relevance: HIGH - As Found: Respiratory Failure - ID: M9421 - Name: Heart Failure - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M9411 - Name: Heart Arrest - Relevance: LOW - As Found: Unknown - ID: M15577 - Name: Shock - Relevance: LOW - As Found: Unknown - ID: M15578 - Name: Shock, Cardiogenic - Relevance: HIGH - As Found: Cardiogenic Shock - ID: M28144 - Name: Acute Lung Injury - Relevance: HIGH - As Found: Acute Respiratory Distress Syndrome - ID: M28143 - Name: Lung Injury - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M25869 - Name: Premature Birth - Relevance: LOW - As Found: Unknown - ID: M10279 - Name: Infant, Premature, Diseases - Relevance: LOW - As Found: Unknown - ID: M10276 - Name: Infant, Newborn, Diseases - Relevance: LOW - As Found: Unknown - ID: M12155 - Name: Myocardial Infarction - Relevance: LOW - As Found: Unknown - ID: M10282 - Name: Infarction - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: LOW - As Found: Unknown - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown - ID: T4927 - Name: Respiratory Distress Syndrome, Infant - Relevance: HIGH - As Found: Respiratory Distress Syndrome - ID: T192 - Name: Acute Respiratory Distress Syndrome - Relevance: HIGH - As Found: Acute Respiratory Distress Syndrome - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012128 - Term: Respiratory Distress Syndrome - ID: D000012127 - Term: Respiratory Distress Syndrome, Newborn - ID: D000012131 - Term: Respiratory Insufficiency - ID: D000055371 - Term: Acute Lung Injury - ID: D000012770 - Term: Shock, Cardiogenic ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04012879 **Brief Title:** Study Evaluating the Efficacy and Safety With CD19CAR-T for Relapsed or Refractory Acute Lymphoblastic Leukemia **Official Title:** Study Evaluating the Efficacy and Safety With CD19CAR-T for Relapsed or Refractory Acute Lymphoblastic Leukemia #### Organization Study ID Info **ID:** HEM-ALL001-CART #### Organization **Class:** OTHER **Full Name:** Chinese PLA General Hospital ### Status Module #### Completion Date **Date:** 2021-06-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-07-09 **Type:** ACTUAL **Last Update Submit Date:** 2019-07-07 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2019-05-01 **Type:** ACTUAL **Status Verified Date:** 2019-07 #### Study First Post Date **Date:** 2019-07-09 **Type:** ACTUAL **Study First Submit Date:** 2019-06-28 **Study First Submit QC Date:** 2019-07-07 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Shenzhen University General Hospital #### Lead Sponsor **Class:** OTHER **Name:** Chinese PLA General Hospital #### Responsible Party **Investigator Affiliation:** Chinese PLA General Hospital **Investigator Full Name:** Li Yu **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study is a single-arm, open label, phase I clinical trial to evaluate the safety and feasibility of CD19CAR-T in treatment of relapsed / refractory acute lymphoblasic leukemia. ### Conditions Module **Conditions:** - Relapsed Acute Lymphoblastic Leukemia - Refractory Acute Lymphoblastic Leukemia ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 12 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** After 6 days of pre-chemotherapy, patients in study group will be injected with CD19CART cell at the dose of 5×10\^4 cells/kg in 36-96 hours **Intervention Names:** - Combination Product: CD19 CART **Label:** study group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - study group **Description:** CD19 CART **Name:** CD19 CART **Type:** COMBINATION_PRODUCT ### Outcomes Module #### Primary Outcomes **Description:** the recovery rate of patients consists of complete recovery rate and partial recovery rate of patients being treated with CD19 CAR-T **Measure:** recovery rate of patients being treated with CD19CAR-T **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Diagnosis with Relapsed or refractory acute lymphocyte leukemia with CD19 positive 2. Age 18 to 65 years old, both male and female; 3. Is expected to survive more than 12 weeks; 4. Physical condition is good: 0-1 score ECOG score; 5. No obvious abnormal heart, liver, kidney, no large wounds that haven't healed on the body; 6. Into groups to participate in voluntarily, good adherence, can cooperate test observation, childbearing age women must be 7 days before starting treatment expert pregnancy test and the results were negative, and signed a written informed consent form. Exclusion Criteria: 1. Organ failure, such as heart: Class III and IV; liver: to Child grading of liver function grade C; kidney: kidney failure and uremia stage; lung: symptoms of severe respiratory failure; brain: disorder of consciousness; 2. Existing serious acute infection, uncontrollable, or have fester sex and chronic infection, wound in delay no more; 3. Pregnancy and lactation women; 4. Patients who have participated in other clinical trials or other clinical trials in the past 30 days; 5. The Investigator believe the patients should not participate in this experiment. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** wanglixin1991@sohu.com **Name:** Lixing Wang, M.D. **Phone:** 86-0755-21839178 **Role:** CONTACT #### Locations **Location 1:** **City:** Shenzhen **Contacts:** ***Contact 1:*** - **Email:** wanglixin1991@sohu.com - **Name:** Lixing Wang, M.D. - **Phone:** 86-0755-21839178 - **Role:** CONTACT ***Contact 2:*** - **Name:** Li Yu, M.D. Ph.D. - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Lixing Wang, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Shenzhen University General Hospital **Status:** RECRUITING **Zip:** 518000 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: HIGH - As Found: Lymphoblastic Leukemia - ID: M27585 - Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T175 - Name: Acute Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: T3533 - Name: Lymphoblastic Lymphoma - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000054198 - Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma - ID: D000007945 - Term: Leukemia, Lymphoid ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03821779 **Acronym:** POSAD **Brief Title:** Prefrontal Oscillations in Social Anxiety Disorder (POSAD) **Official Title:** Study of Slow Prefrontal Cortex Oscillations During Social Exposure in Social Anxiety Disorder #### Organization Study ID Info **ID:** C17-25 #### Organization **Class:** OTHER_GOV **Full Name:** Institut National de la Santé Et de la Recherche Médicale, France ### Status Module #### Completion Date **Date:** 2021-12-10 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-11-26 **Type:** ACTUAL **Last Update Submit Date:** 2019-11-22 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-11-10 **Type:** ESTIMATED #### Start Date **Date:** 2019-11-12 **Type:** ACTUAL **Status Verified Date:** 2019-11 #### Study First Post Date **Date:** 2019-01-30 **Type:** ACTUAL **Study First Submit Date:** 2018-11-29 **Study First Submit QC Date:** 2019-01-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Institut National de la Santé Et de la Recherche Médicale, France #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Experimental fear in rodents is correlated with slow oscillations in electrical recordings of prefrontal cortex activities. The present study aims to test whether slow prefrontal oscillations is a biomarker of pathological anxiety in human subjects. **Detailed Description:** Fear and anxiety are adaptive responses that may become excessive or inappropriate in pathological conditions, as defined as anxiety disorders in DSM-5. These disorders, including phobic disorders such as social anxiety disorder, are frequent and impairing in the general population, with an estimated lifetime prevalence of 28% and significant consequences on quality of life. Direct and indirect medical costs related to these conditions amount to 74.4 billion €/year in Europe. Despite their prevalence, debilitating nature and chronicity, the pathophysiology of anxiety disorders is poorly understood and neurobiological treatments, including pharmacotherapy, are lacking efficacy. A better understanding of the neuronal mechanisms implicated in anxiety is necessary for the conception of new approaches to treat pathological anxiety. Anxiety is commonly modeled in animals using fear conditioning, which consists in associating a neutral stimulus (eg: a sound) with a mild electrical foot-shock. As a result of the association between sound and shock, sound presentation in isolation induces a set of conditioned behavioral responses, such as an immobilization ("freezing"). Previous studies have shown that the expression of fear responses, measured on the basis of freezing, is associated with the emergence of slow oscillations (2-6Hz) in medial prefrontal cortex (mPFC) of mice. Moreover, emergence of these oscillations in mPFC is predictive of the occurrence of freezing, and the artificial induction of 4 Hz oscillations in mPFC with optogenetics induces freezing. Finally, inhibiting neurons in mPFC during the ascending phase of this slow mPFC oscillation at the time of conditioned sound presentation is sufficient to significantly reduce fear. Interestingly, these results obtained in mice seem to find their prolongation in humans. Recent studies using fear conditioning in human subjects have also reported the emergence of prefrontal slow oscillations between 2-6 Hz during expression of conditioned fear responses. These results suggests that common mechanisms underlie the expression of fear in humans and rodents. However, whether similar neuronal circuits and mechanisms are implicated in human anxiety disorders remains unknown. This study aims at assessing the presence of slow mPFC oscillations during expression of anxiety in patients suffering from anxiety disorders. Beyond understanding of the neuronal mechanisms underlying anxiety expression, this study could provide a biomarker of anxiety with diagnostic and therapeutic implications. ### Conditions Module **Conditions:** - Anxiety Disorders - Anxiety - Anxiety and Fear ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SEQUENTIAL **Intervention Model Description:** First phase (go-no-go) with 10 subjects in 1 arm Second phase with 20 subjets (2 arms) in a cross-over design. ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The presence of significant prefrontal oscillations in the EEG recording 2-6Hz band during in vivo social exposure (oral presentation to examiners) will be assessed in 10 subjects with social anxiety disorder. EEG will be recorded immediately before, during and after oral presentations to examiners. Psychometric evaluation will be performed prior to experimental sessions. Rating of anxiety levels will be performed by subjects using a Visual Analogue Scale of anxiety during each of the 3 experimental periods (wainting, presentation, recovery). Results of EEG recordings in the first 10 subjects will lead to continuation (presence of significant slow prefrontal oscillations during anxiety) or interruption (absence of signification oscillation) of the study. **Intervention Names:** - Behavioral: In vivo social exposure - Other: EEG recording - Diagnostic Test: Psychometric evaluation - Diagnostic Test: Visual Analogue Scale of anxiety **Label:** Group 1: Go-no-go phase **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** In group 2.1, 10 subjects will undergo 2 sessions in a cross-over design with EEG recording immediately before, during and after: 1. "real exposure": oral presentation to a panel of examiners 2. "virtual reality" : oral presentation to virtual examiners Rating of anxiety levels will be performed by subjects using a Visual Analogue Scale of anxiety during each of the 3 experimental periods for each session. Psychometric evaluation will be performed prior to experimental sessions. **Intervention Names:** - Behavioral: In vivo social exposure - Behavioral: Social exposure in a virtual reality setting - Other: EEG recording - Diagnostic Test: Psychometric evaluation - Diagnostic Test: Visual Analogue Scale of anxiety **Label:** Group 2.1 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** In group 2.2, 10 subjects will undergo 2 sessions in a cross-over design with EEG recording immediately before, during and after: 1. "virtual reality" : oral presentation to virtual examiners 2. "real exposure": oral presentation to a panel of examiners Rating of anxiety levels will be performed by subjects using a Visual Analogue Scale of anxiety during each of the 3 experimental periods for each session. Psychometric evaluation will be performed prior to experimental sessions. **Intervention Names:** - Behavioral: In vivo social exposure - Behavioral: Social exposure in a virtual reality setting - Other: EEG recording - Diagnostic Test: Psychometric evaluation - Diagnostic Test: Visual Analogue Scale of anxiety **Label:** Group 2.2 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1: Go-no-go phase - Group 2.1 - Group 2.2 **Description:** Subjects will be invited to give a 5 minutes oral presentation on the topic of their choice to five examiners displaying no facial emotional reaction, after a 5 minutes period of silent waiting in front of the examiners. This waiting period is prompt to elicit anticipation-type of social anxiety. **Name:** In vivo social exposure **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Group 2.1 - Group 2.2 **Description:** Subjects will give a 5 minutes oral presentation on the subject of their choice to a virtual reality panel composed of 5 examiners displaying no facial emotional reaction, after a 5 minutes period of silent waiting in front of the examiners. This waiting period is expected to elicit anticipation-type of social anxiety. **Name:** Social exposure in a virtual reality setting **Type:** BEHAVIORAL #### Intervention 3 **Arm Group Labels:** - Group 1: Go-no-go phase - Group 2.1 - Group 2.2 **Description:** EEG will be recorded with a standard 16-electrodes cap. Recordings will start before the 5 minutes waiting period and continue throughout oral presentation and recovery. The recovery period will be used as a baseline control **Name:** EEG recording **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Group 1: Go-no-go phase - Group 2.1 - Group 2.2 **Description:** Subjects will be evaluated prior to inclusion using the following assessment tools * Anamnestic Association for Methodology and Documentation in Psychiatry (AMDP) questionnaire * Mini International Neuropsychiatric Interview (MINI 6.0, for psychiatric diagnoses) * Liebowitz Social Anxiety Scale (LSAS) * Montgomery Asberg Depression Rating Scale (MADRS) * Brief Anxiety Scale of Tyrer (BAS) * State-Trait Anxiety Inventory (STAI A-B) * Global Assessment of Functioning (GAF) **Name:** Psychometric evaluation **Type:** DIAGNOSTIC_TEST #### Intervention 5 **Arm Group Labels:** - Group 1: Go-no-go phase - Group 2.1 - Group 2.2 **Description:** Subjects will be asked to rate their anxiety levels * immediately before (5 minutes of silent waiting), * during * and after the 5-minute oral presentation (recovery) **Name:** Visual Analogue Scale of anxiety **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Other Outcomes **Description:** The change in power of PFC 2-6 Hz oscillations between the 5-minutes oral presentation and the recovery period will be computed as a ratio. **Measure:** Change in power of slow oscillations in prefrontal EEG recordings during presentation relative to baseline **Time Frame:** During the 5 minutes oral presentation and during the 1 hour rest period. **Description:** Time-frequency analysis will be performed to determine the duration of 2-6Hz prefrontal oscillations epochs and total duration of these oscillations within experimental period. Significant oscillatory epochs will be defined using power ratios. **Measure:** Duration of prefrontal slow oscillations epochs during presentation **Time Frame:** During the 5 minutes oral presentation **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power and the visual Analogue anxiety score during the 5 minutes period before presentation. **Measure:** Correlation between prefrontal slow oscillations power during anticipation and anxiety score **Time Frame:** During the 5 minutes before oral presentation **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power and the visual Analogue anxiety score during presentation. **Measure:** Correlation between prefrontal slow oscillations power during presentation and anxiety score **Time Frame:** During the 5 minutes oral presentation **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration and the visual Analogue anxiety score during the 5 minutes period before presentation. **Measure:** Correlation between prefrontal slow oscillations duration during anticipation and anxiety score **Time Frame:** During the 5 minutes before oral presentation **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration and the visual Analogue anxiety score during presentation. **Measure:** Correlation between prefrontal slow oscillations duration during presentation and anxiety score **Time Frame:** During the 5 minutes oral presentation **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and STAI-B scores **Measure:** Correlation between prefrontal slow oscillations power during anticipation and trait anxiety **Time Frame:** During the 5 minutes before oral presentations (PFC oscillations power) and prior to inclusion (STAI-B rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and STAI-B scores **Measure:** Correlation between prefrontal slow oscillations power during presentation and trait anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (STAI-B rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and STAI-B scores **Measure:** Correlation between prefrontal slow oscillations duration during anticipation and trait anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (STAI-B rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and STAI-B scores **Measure:** Correlation between prefrontal slow oscillations duration during presentation and trait anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (STAI-B rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and STAI-A scores **Measure:** Correlation between prefrontal slow oscillations power during anticipation and state anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (STAI-A rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and STAI-A scores **Measure:** Correlation between prefrontal slow oscillations power during presentation and state anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (STAI-A rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and STAI-A scores **Measure:** Correlation between prefrontal slow oscillations duration during anticipation and state anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (STAI-A rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and STAI-A scores **Measure:** Correlation between prefrontal slow oscillations duration during presentation and state anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (STAI-A rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and LSAS scores **Measure:** Correlation between prefrontal slow oscillations power during anticipation and levels of social anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (LSAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and LSAS scores **Measure:** Correlation between prefrontal slow oscillations power during presentation and levels of social anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (LSAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and LSAS scores **Measure:** Correlation between prefrontal slow oscillations duration during anticipation and levels of social anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (LSAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and LSAS scores **Measure:** Correlation between prefrontal slow oscillations duration during presentation and levels of social anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (LSAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and BAS scores **Measure:** Correlation between prefrontal slow oscillations power during anticipation and levels of general anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (BAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and BAS scores **Measure:** Correlation between prefrontal slow oscillations power during presentation and levels of general anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (BAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and BAS scores **Measure:** Correlation between prefrontal slow oscillations duration during anticipation and levels of general anxiety **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (BAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and BAS scores **Measure:** Correlation between prefrontal slow oscillations duration during presentation and levels of general anxiety **Time Frame:** During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (BAS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and MADRS scores **Measure:** Correlation between prefrontal slow oscillations power during anticipation and depression levels **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (MARDS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations power during presentations and MADRS scores **Measure:** Correlation between prefrontal slow oscillations power during presentation and depression levels **Time Frame:** During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (MARDS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and MADRS scores **Measure:** Correlation between prefrontal slow oscillations duration during anticipation and depression levels **Time Frame:** During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (MARDS rating) **Description:** Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and MADRS scores **Measure:** Correlation between prefrontal slow oscillations duration during presentation and depression levels **Time Frame:** During the 5 minutes oral presentations (PFC oscillations duration) and prior to inclusion (MARDS rating) #### Primary Outcomes **Description:** The change in power of PFC 2-6 Hz oscillations between the 5-minutes waiting period before oral presentation and the recovery period will be computed as a ratio. Detection of exaggerated 2-6Hz oscillations in prefrontal cortex during anxious anticipation is the primary aim of this study. **Measure:** Change in power of slow oscillations in prefrontal EEG recordings during anticipation relative to baseline **Time Frame:** During the 5 minutes before oral presentation and during the 1 hour rest period #### Secondary Outcomes **Description:** Time-frequency analysis will be performed to determine the duration of 2-6Hz prefrontal oscillations epochs and total duration of these oscillations within experimental period. Significant oscillatory epochs will be defined using power ratios. These metrics will be used in order to assess the neurobiological and clinical relevance of this biomarker. **Measure:** Duration of prefrontal slow oscillations epochs during anticipation **Time Frame:** During the 5 minutes before oral presentation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Social anxiety disorder as defined in DSM-5 * Full understanding of the protocol * Obtaining informed consent from study subjects before or at inclusion at the latest * Being registered in the french national health insurance service (Sécurité Sociale) (or equivalent) Exclusion Criteria: * Active medical co-morbidity including severe hypertension, cardiac insufficiency, Raynaud syndrome, diabetes mellitus, renal insufficiency, adrenal insufficiency, Cushing syndrome and epilepsy * Severe neurological co-morbidity, including but not limited to Parkinson's disease and multiple sclerosis * Long-term corticotherapy * History of significant head injury, defined by loss of consciousness * Being diagnosed with another major psychiatric condition (DSM5) including bipolar disorder and schizophrenia or substance/alcohol use disorder; with the exception of major depressive disorder and nicotine use disorder * Suicidal risk evaluated as moderate to high in the MINI questionnaire * initiation of a psychotropic treatment or change in the dose of ongoing psychotropic treatment within 3 days prior to each visit and including: 1. antidepressant treatments with selective serotonin recapture inhibitors, serotonin and norepinephrine inhibitors, alpha2-presynaptic adrenoreceptors (mirtazapine, mianserin), tricyclic 2. anxiolytic drugs including benzodiazepines and anti-histamine 3. antipsychotic drugs * Acute alcohol intake 2 days prior to each visit (inclusion, experimental sessions) * Pregnancy or breastfeeding. * Ongoing hospitalization without consent (decision of a third-party: medical, justice) **Maximum Age:** 50 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** bruno.aouizerate@u-bordeaux.fr **Name:** Bruno Aouizerate, MD-PhD **Phone:** +33(0) 5 56 56 17 98 **Role:** CONTACT **Contact 2:** **Email:** cyril.herry@inserm.fr **Name:** Cyril Herry, PhD **Phone:** 33(0)5 57 57 37 26 **Role:** CONTACT #### Locations **Location 1:** **City:** Bordeaux **Contacts:** ***Contact 1:*** - **Email:** pierre.philip@chu-bordeaux.fr - **Name:** Pierre Philip, MD-PhD - **Phone:** +33 5 57 82 01 73 - **Role:** CONTACT ***Contact 2:*** - **Email:** jacques.taillard@chu-bordeaux.fr - **Name:** Jacques Taillard, MS - **Role:** CONTACT **Country:** France **Facility:** GENPHASS, SANPSY, CHU de Bordeaux **Status:** RECRUITING **Zip:** 33076 #### Overall Officials **Official 1:** **Affiliation:** Centre Hospitalier Charles Perrens, Bordeaux; INRA NutriNeuro, Bordeaux; Université de Bordeaux, France **Name:** Olivier Doumy, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Centre Hospitalier Charles Perrens, Bordeaux; Université de Bordeaux, France **Name:** Alexandra Bouvard, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Neurocentre Magendie, Inserm U1215, Bordeaux, France **Name:** Cyril Herry, PhD **Role:** STUDY_DIRECTOR **Official 4:** **Affiliation:** Neurocentre Magendie, Inserm U1215, Bordeaux, France **Name:** Cyril Dejean, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 5:** **Affiliation:** Centre Hospitalier Charles Perrens, Bordeaux; Neurocentre Magendie, Inserm U1215, Bordeaux, France **Name:** Thomas Bienvenu, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 6:** **Affiliation:** GENPHASS, CHU de Bordeaux **Name:** Jacques Taillard, MS **Role:** PRINCIPAL_INVESTIGATOR **Official 7:** **Affiliation:** Centre Hospitalier Charles Perrens, Bordeaux; INRA NutriNeuro, Bordeaux; Université de Bordeaux, France **Name:** Bruno Aouizerate, MD-PhD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001523 - Term: Mental Disorders - ID: D000010698 - Term: Phobic Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4324 - Name: Anxiety Disorders - Relevance: HIGH - As Found: Anxiety Disorder - ID: M1117 - Name: Phobia, Social - Relevance: HIGH - As Found: Social Anxiety Disorder - ID: M13603 - Name: Phobic Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001008 - Term: Anxiety Disorders - ID: D000072861 - Term: Phobia, Social ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04184479 **Acronym:** LEVA-POP **Brief Title:** Effect of the LEVAmethod by Bertz et al © in Subjects With Overweight or Obesity in Primary Health Care. **Official Title:** Placebo-Controlled, Randomized Weight Loss InterventionTrial in Subjects With Overweight or Obesity in Primary Health Care #### Organization Study ID Info **ID:** LEVA-POP #### Organization **Class:** OTHER_GOV **Full Name:** Vastra Gotaland Region ### Status Module #### Completion Date **Date:** 2025-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Start Date **Date:** 2020-12-02 **Type:** ACTUAL **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2019-12-03 **Type:** ACTUAL **Study First Submit Date:** 2019-11-24 **Study First Submit QC Date:** 2019-11-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Vastra Gotaland Region #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study evaluates weight loss effect of the method LEVA by Bertz et al in subjects with overweight or obesity that are remitted to Primärvårdens Dietistenhet. **Detailed Description:** The method "Lifestyle at Effective Weight Loss During Breastfeeding" (LEVA method by Bertz et al) has been scientifically studied to provide sustainable weight loss for women with overweight or obesity after childbirth. Primary health care centers in Västra Götalandsregionen treat adult patients with overweight and obesity. If the LEVA method by Bertz et el also produces weight loss to other patient groups than women post partum, the method could be used as a treatment alternative. ### Conditions Module **Conditions:** - Overweight and Obesity **Keywords:** - overweight - randomized controlled trial - obesity - weight loss - weight loss maintenance ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individual dietary advices for weight loss, based on the participants' food record of 4 consecutive days aimed to achieve an energy intake reduction of 500 kcal/d with a nutrient composition according to the Nordic Nutrition Recommendations. Follow up visits after 3 months, 1 year and 2 years after baseline. Follow up by electronic platform every other week until 3 months after baseline and each month after 3 months until 1 year after baseline. **Intervention Names:** - Behavioral: LEVAmethod by Bertz et al **Label:** A-LEVAmetoden by Bertz et al **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Dietary advices for weight loss aimed to achieve calorie restriction. Follow up visits after 3 months, 1 year and 2 years after baseline. Additional visits, up to 4 times in the first year after baseline. **Intervention Names:** - Behavioral: LEVAmethod by Bertz et al **Label:** B-Ordinary treatment **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - A-LEVAmetoden by Bertz et al - B-Ordinary treatment **Description:** Ordinary treatment **Name:** LEVAmethod by Bertz et al **Other Names:** - Ordinary treatment **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Weight in kg measured at visits **Measure:** Change of weight between intervention group and placebo **Time Frame:** From baseline and 12 weeks **Description:** Weight in kg measured at visits **Measure:** Change of weight between intervention group and placebo **Time Frame:** From baseline and 1 year **Description:** Weight in kg measured at visits **Measure:** Change of weight between intervention group and placebo **Time Frame:** From baseline and 2 year #### Secondary Outcomes **Description:** weight in kg measured at visits in relation to gender **Measure:** Gender differences in weight loss results **Time Frame:** From baseline to 12 weeks **Description:** weight in kg measured at visits in relation to gender **Measure:** Gender differences in weight loss results **Time Frame:** From baseline to 1 year **Description:** weight in kg measured at visits in relation to gender **Measure:** Gender differences in weight loss results **Time Frame:** From baseline to 2 year **Description:** Weight in kg measured at visits in relation to age **Measure:** Age differences in weight loss results **Time Frame:** From baseline to 12 weeks **Description:** Weight in kg measured at visits in relation to age **Measure:** Age differences in weight loss results **Time Frame:** From baseline to 1 years **Description:** Weight in kg measured at visits in relation to age **Measure:** Age differences in weight loss results **Time Frame:** From baseline to 2 years **Description:** Weight in kg measured at visits in relation to pre-treatment BMI **Measure:** Weight loss result in relation to pre-treatment BMI **Time Frame:** From baseline to 12 weeks **Description:** Weight in kg measured at visits in relation to pre-treatment BMI **Measure:** Weight loss result in relation to pre-treatment BMI **Time Frame:** From baseline to 1 year **Description:** Weight in kg measured at visits in relation to pre-treatment BMI **Measure:** Weight loss result in relation to pre-treatment BMI **Time Frame:** From baseline to 2 year **Description:** Calculation of cost-effectiveness by the method of monetary net benefit **Measure:** Cost-effectiveness of LEVA method by Bertz et al **Time Frame:** From baseline to 12 weeks **Description:** Calculation of cost-effectiveness by the method of monetary net benefit **Measure:** Cost-effectiveness of LEVA method by Bertz et al **Time Frame:** From baseline to 1 year **Description:** Calculation of cost-effectiveness by the method of monetary net benefit **Measure:** Cost-effectiveness of LEVA method by Bertz et al **Time Frame:** From baseline to 2 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * BMI 27 ≤ 35 * age 18-75 år Exclusion Criteria: * difficulty understanding Swedish, spoken or read * does not manage/want to handle digital Tools * the remittance was addressed to Primärvårdens Dietistenhet at wrong premises and the patient should be treated elsewhere. **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** else.hellebo.johansson@vgregion.se **Name:** Else Johansson **Phone:** +46768871219 **Role:** CONTACT #### Locations **Location 1:** **City:** Göteborg **Contacts:** ***Contact 1:*** - **Email:** else.hellebo.johansson@vgregion.se - **Name:** Else Johansson - **Phone:** +46768871219 - **Role:** CONTACT **Country:** Sweden **Facility:** Västra Götalandsregionen **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Västra Götalandsregionen **Name:** Else Johansson **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M18102 - Name: Weight Loss - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: HIGH - As Found: Obesity - ID: M26186 - Name: Overweight - Relevance: HIGH - As Found: Overweight - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009765 - Term: Obesity - ID: D000050177 - Term: Overweight ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03434379 **Acronym:** IMbrave150 **Brief Title:** A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma **Official Title:** A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma #### Organization Study ID Info **ID:** YO40245 #### Organization **Class:** INDUSTRY **Full Name:** Hoffmann-La Roche #### Secondary ID Infos **ID:** 2017-003691-31 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2022-11-17 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-23 **Type:** ACTUAL **Last Update Submit Date:** 2023-10-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-08-31 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-11-05 **Type:** ACTUAL **Results First Submit Date:** 2021-08-16 **Results First Submit QC Date:** 2021-10-07 #### Start Date **Date:** 2018-03-15 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2018-02-15 **Type:** ACTUAL **Study First Submit Date:** 2018-01-31 **Study First Submit QC Date:** 2018-02-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment. **Detailed Description:** The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A (experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib ### Conditions Module **Conditions:** - Carcinoma, Hepatocellular ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 558 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator **Intervention Names:** - Drug: Atezolizumab - Drug: Bevacizumab **Label:** Atezolizumab + Bevacizumab **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator **Intervention Names:** - Drug: Sorafenib **Label:** Sorafenib **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Atezolizumab + Bevacizumab **Description:** Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle **Name:** Atezolizumab **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Atezolizumab + Bevacizumab **Description:** Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle **Name:** Bevacizumab **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Sorafenib **Description:** Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle **Name:** Sorafenib **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** OS was defined as the time from randomization to death from any cause. **Measure:** Overall Survival (OS) in the Global Population **Time Frame:** From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** OS was defined as the time from randomization to death from any cause. **Measure:** Overall Survival (OS) in the China Population **Time Frame:** From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** PFS-IRF Per RECIST v1.1 in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) #### Secondary Outcomes **Description:** ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Measure:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Measure:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the Global Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Measure:** ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Measure:** Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Measure:** Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the Global Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Measure:** Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** PFS-IRF Per HCC mRECIST in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** TTP-IRF Per HCC mRECIST in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** OS was defined as the time from randomization to death from any cause. Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed. **Measure:** Overall Survival by Baseline AFP in the Global Population **Time Frame:** From randomization to death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed. **Measure:** PFS-IRF Per RECIST v1.1 by Baseline AFP in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed. **Measure:** PFS-INV Per RECIST v1.1 by Baseline AFP in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** TTD was defined as the time from randomization to the first deterioration (decrease from baseline of \>/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks. **Measure:** Time to Deterioration (TTD) in the Global Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. **Measure:** Number of Participants With Adverse Events (AEs) in the Global Population **Time Frame:** Up to end of study (up to approximately 56 months) **Measure:** Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population **Time Frame:** Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) **Measure:** Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population **Time Frame:** Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) **Measure:** Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population **Time Frame:** Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 30 months) **Description:** ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Measure:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the China Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Measure:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the China Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Measure:** ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the China Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Measure:** Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the China Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Measure:** Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the China Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Measure:** Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the China Population **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** PFS-IRF Per HCC mRECIST in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** TTP-IRF Per HCC mRECIST in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Measure:** TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** TTD was defined as the time from randomization to the first deterioration (decrease from baseline of \>/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks. **Measure:** Time to Deterioration (TTD) in the China Population **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Description:** An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. **Measure:** Number of Participants With Adverse Events (AEs) in the China Population **Time Frame:** Up to end of study (up to approximately 56 months) **Measure:** Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population **Time Frame:** Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) **Measure:** Trough Serum Concentration (Cmin) of Atezolizumab in the China Population **Time Frame:** Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) **Measure:** Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population **Time Frame:** Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 18 months) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) * No prior systemic therapy for HCC. Previous use of herbal therapies/traditional Chinese medicines with anti-cancer activity included in the label is allowed, provided that these medications are discontinued prior to randomization. * At least one measurable untreated lesion * ECOG Performance Status of 0 or 1 * Adequate hematologic and end-organ function * For women of childbearing potential: agreement to remain abstinent * For men: agreement to remain abstinent * Child-Pugh class A Exclusion Criteria: * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan * Known active tuberculosis * History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death * Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last dose of sorafenib * Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding * A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment. * Moderate or severe ascites * History of hepatic encephalopathy * Co-infection of HBV and HCV * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * Uncontrolled tumor-related pain * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures * Uncontrolled or symptomatic hypercalcemia * Treatment with systemic immunostimulatory agents * Inadequately controlled arterial hypertension * Prior history of hypertensive crisis or hypertensive encephalopathy * Evidence of bleeding diathesis or significant coagulopathy * History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration * Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture * Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses * Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure * Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID) **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Phoenix **Country:** United States **Facility:** St. Josephs Hospital and Medical Center **State:** Arizona **Zip:** 85260 **Location 2:** **City:** Duarte **Country:** United States **Facility:** City of Hope **State:** California **Zip:** 91010 **Location 3:** **City:** La Jolla **Country:** United States **Facility:** Uni of California - San Diego; Cancer Center & Dept of Medicine **State:** California **Zip:** 92093 **Location 4:** **City:** Novato **Country:** United States **Facility:** Kaiser Permanente Northern California **State:** California **Zip:** 94589 **Location 5:** **City:** Orange **Country:** United States **Facility:** University of California Irvine Medical Center **State:** California **Zip:** 92868 **Location 6:** **City:** Sacramento **Country:** United States **Facility:** Kaiser Permanente Sacramento Medical Center **State:** California **Zip:** 95825 **Location 7:** **City:** San Francisco **Country:** United States **Facility:** California Pacific Medical Center **State:** California **Zip:** 94115 **Location 8:** **City:** San Francisco **Country:** United States **Facility:** Kaiser Permanente - San Francisco Medical Center **State:** California **Zip:** 94118 **Location 9:** **City:** Santa Monica **Country:** United States **Facility:** University of California Los Angeles **State:** California **Zip:** 90404 **Location 10:** **City:** Walnut Creek **Country:** United States **Facility:** Kaiser Permanente - Walnut Creek **State:** California **Zip:** 94596 **Location 11:** **City:** Greeley **Country:** United States **Facility:** Banner MD Anderson Cancer Center **State:** Colorado **Zip:** 85234 **Location 12:** **City:** Washington **Country:** United States **Facility:** Georgetown University **State:** District of Columbia **Zip:** 20007 **Location 13:** **City:** Tampa **Country:** United States **Facility:** Moffitt Cancer Center **State:** Florida **Zip:** 33612 **Location 14:** **City:** Boston **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Zip:** 02114 **Location 15:** **City:** Detroit **Country:** United States **Facility:** Henry Ford Health System **State:** Michigan **Zip:** 48202 **Location 16:** **City:** Saint Louis **Country:** United States **Facility:** Washington University; Wash Uni. Sch. Of Med **State:** Missouri **Zip:** 63110 **Location 17:** **City:** Albuquerque **Country:** United States **Facility:** University of New Mexico Comprehensive Cancer Center **State:** New Mexico **Zip:** 87102 **Location 18:** **City:** New York **Country:** United States **Facility:** Laura and ISAAC Perlmutter Cancer Center at NYU Langone. **State:** New York **Zip:** 10016 **Location 19:** **City:** Philadelphia **Country:** United States **Facility:** Thomas Jefferson University **State:** Pennsylvania **Zip:** 19107 **Location 20:** **City:** Houston **Country:** United States **Facility:** M.D Anderson Cancer Center; Uni of Texas At Houston **State:** Texas **Zip:** 77030 **Location 21:** **City:** Seattle **Country:** United States **Facility:** Swedish Cancer Inst. **State:** Washington **Zip:** 98104 **Location 22:** **City:** Bankstown **Country:** Australia **Facility:** Bankstown-Lidcombe Hospital **State:** New South Wales **Zip:** 2200 **Location 23:** **City:** Kogarah **Country:** Australia **Facility:** St George Hospital **State:** New South Wales **Zip:** 2217 **Location 24:** **City:** Woodville **Country:** Australia **Facility:** The Queen Elizabeth Hospital **State:** South Australia **Zip:** 5011 **Location 25:** **City:** St Albans **Country:** Australia **Facility:** Sunshine Hospital **State:** Victoria **Zip:** 3021 **Location 26:** **City:** Ottawa **Country:** Canada **Facility:** Ottawa Hospital Research Institute **State:** Ontario **Zip:** K1Y 4E9 **Location 27:** **City:** Montreal **Country:** Canada **Facility:** Centre hospitalier de l'Universite de Montreal (CHUM) **State:** Quebec **Zip:** H2X 0A9 **Location 28:** **City:** Montreal **Country:** Canada **Facility:** Jewish General Hospital **State:** Quebec **Zip:** H3T 1E2 **Location 29:** **City:** Montreal **Country:** Canada **Facility:** McGill University Health Centre - Glen Site **State:** Quebec **Zip:** H4A 3J1 **Location 30:** **City:** Beijing City **Country:** China **Facility:** Peking Union Medical College Hospital **Zip:** 100032 **Location 31:** **City:** Beijing **Country:** China **Facility:** Beijing Friendship Hospital **Zip:** 100050 **Location 32:** **City:** Beijing **Country:** China **Facility:** Beijing Cancer Hospital **Zip:** 100142 **Location 33:** **City:** Changchun **Country:** China **Facility:** the First Hospital of Jilin University **Zip:** 130021 **Location 34:** **City:** Changchun **Country:** China **Facility:** Jilin Cancer Hospital **Zip:** 132013 **Location 35:** **City:** Changsha CITY **Country:** China **Facility:** Hunan Cancer Hospital **Zip:** 410013 **Location 36:** **City:** Foshan **Country:** China **Facility:** The First People's Hospital of Foshan; Local Ethic Committee **Zip:** 510000 **Location 37:** **City:** Fuzhou **Country:** China **Facility:** The 900th Hospital of PLA joint service support force **Zip:** 110016 **Location 38:** **City:** Guangzhou City **Country:** China **Facility:** Sun Yet-sen University Cancer Center **Zip:** 510663 **Location 39:** **City:** Guangzhou **Country:** China **Facility:** Nanfang Hospital, Southern Medical University **Zip:** 510515 **Location 40:** **City:** Hangzhou City **Country:** China **Facility:** Sir Run Run Shaw Hospital **Zip:** 310018 **Location 41:** **City:** Hangzhou City **Country:** China **Facility:** Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department **Zip:** 310022 **Location 42:** **City:** Hangzhou **Country:** China **Facility:** The First Affiliated Hospital of College of Medicine, Zhejiang University **Zip:** 310003 **Location 43:** **City:** Harbin **Country:** China **Facility:** Harbin Medical University Cancer Hospital **Zip:** 150081 **Location 44:** **City:** Hefei City **Country:** China **Facility:** Anhui Province Cancer Hospital **Zip:** 230031 **Location 45:** **City:** Hefei **Country:** China **Facility:** The First Affiliated Hospital of Anhui Medical University **Zip:** 230022 **Location 46:** **City:** Jinan **Country:** China **Facility:** General Hospital of Jinan Military Command of PLA **Zip:** 250031 **Location 47:** **City:** Nanjing City **Country:** China **Facility:** The 81st Hospital of P.L.A. **Zip:** 210002 **Location 48:** **City:** Shanghai City **Country:** China **Facility:** Fudan University Shanghai Cancer Center **Zip:** 200120 **Location 49:** **City:** Shanghai **Country:** China **Facility:** Zhongshan Hospital Fudan University **Zip:** 200032 **Location 50:** **City:** Wuhan **Country:** China **Facility:** Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech **Zip:** 430030 **Location 51:** **City:** Brno **Country:** Czechia **Facility:** Masarykuv onkologicky ustav **Zip:** 656 53 **Location 52:** **City:** Olomouc **Country:** Czechia **Facility:** Fakultni nemocnice Olomouc; Onkologicka klinika **Zip:** 779 00 **Location 53:** **City:** Lille **Country:** France **Facility:** Hopital Claude Huriez;Gastro Enterologie **Zip:** 59037 **Location 54:** **City:** Lyon **Country:** France **Facility:** Hopital De La Croix Rousse; Hepatologie Gastro Enterologie **Zip:** 69317 **Location 55:** **City:** Marseille **Country:** France **Facility:** Hopital Timone Adultes; Gastro Enterologie **Zip:** 13385 **Location 56:** **City:** Montpellier **Country:** France **Facility:** Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie **Zip:** 34295 **Location 57:** **City:** Nantes **Country:** France **Facility:** Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie **Zip:** 44093 **Location 58:** **City:** Nice Cedex **Country:** France **Facility:** CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie **Zip:** 06202 **Location 59:** **City:** Rouen **Country:** France **Facility:** Hopital Charles Nicolle; Gastroenterologie **Zip:** 76031 **Location 60:** **City:** Strasbourg **Country:** France **Facility:** Hopital Hautepierre; Gastro Enterologie **Zip:** 67098 **Location 61:** **City:** Vandoeuvre-les-nancy **Country:** France **Facility:** Hôpital d'Adultes; Service hépato-gastro-entérologie **Zip:** 54511 **Location 62:** **City:** Villejuif **Country:** France **Facility:** Institut Gustave Roussy; Gastro-Enterologie **Zip:** 94805 **Location 63:** **City:** Berlin **Country:** Germany **Facility:** Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie **Zip:** 13353 **Location 64:** **City:** Frankfurt **Country:** Germany **Facility:** Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I **Zip:** 60590 **Location 65:** **City:** Hamburg **Country:** Germany **Facility:** Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie **Zip:** 20246 **Location 66:** **City:** Hannover **Country:** Germany **Facility:** Med. Hochschule Hannover; Gastroenterologie **Zip:** 30625 **Location 67:** **City:** Leipzig **Country:** Germany **Facility:** Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog. **Zip:** 04103 **Location 68:** **City:** Mainz **Country:** Germany **Facility:** Uniklinik Mainz; I. Medizinische Klinik **Zip:** 55131 **Location 69:** **City:** Regensburg **Country:** Germany **Facility:** Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie **Zip:** 93053 **Location 70:** **City:** Hong Kong **Country:** Hong Kong **Facility:** Queen Mary Hospital; Dept. Of Haematology & Oncology **Location 71:** **City:** Shatin **Country:** Hong Kong **Facility:** Prince of Wales Hosp; Dept. Of Clinical Onc **Location 72:** **City:** Benevento **Country:** Italy **Facility:** Az. Osp. Rummo; Oncologia Medica **State:** Campania **Zip:** 82100 **Location 73:** **City:** Meldola **Country:** Italy **Facility:** IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica **State:** Emilia-Romagna **Zip:** 47014 **Location 74:** **City:** Orbassano **Country:** Italy **Facility:** Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica **State:** Piemonte **Zip:** 10043 **Location 75:** **City:** Cagliari **Country:** Italy **Facility:** A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia **State:** Sardegna **Zip:** 09100 **Location 76:** **City:** Pisa **Country:** Italy **Facility:** Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico **State:** Toscana **Zip:** 56126 **Location 77:** **City:** Padova **Country:** Italy **Facility:** IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima **State:** Veneto **Zip:** 35128 **Location 78:** **City:** Chiba **Country:** Japan **Facility:** Chiba University Hospital **Zip:** 260-8677 **Location 79:** **City:** Chiba **Country:** Japan **Facility:** National Cancer Center Hospital East **Zip:** 277-8577 **Location 80:** **City:** Fukuoka **Country:** Japan **Facility:** Kurume University Hospital **Zip:** 830-0011 **Location 81:** **City:** Hokkaido **Country:** Japan **Facility:** Sapporo Kosei Genaral Hospital **Zip:** 060-0033 **Location 82:** **City:** Hokkaido **Country:** Japan **Facility:** Hokkaido University Hospital **Zip:** 060-8648 **Location 83:** **City:** Ishikawa **Country:** Japan **Facility:** Kanazawa University Hospital **Zip:** 920-8641 **Location 84:** **City:** Kanagawa **Country:** Japan **Facility:** Kitasato University Hospital **Zip:** 252-0375 **Location 85:** **City:** Kumamoto **Country:** Japan **Facility:** Kumamoto University Hospital **Zip:** 860-8556 **Location 86:** **City:** Osaka **Country:** Japan **Facility:** Osaka Metropolitan University Hospital **Zip:** 545-8586 **Location 87:** **City:** Osaka **Country:** Japan **Facility:** Kindai University Hospital **Zip:** 589-8511 **Location 88:** **City:** Saga **Country:** Japan **Facility:** Saga-ken Medical Centre Koseikan **Zip:** 840-8571 **Location 89:** **City:** Shizuoka **Country:** Japan **Facility:** Shizuoka Cancer Center **Zip:** 411-8777 **Location 90:** **City:** Tokyo **Country:** Japan **Facility:** Japanese Red Cross Musashino Hospital **Zip:** 180-8610 **Location 91:** **City:** Jeollanam-do **Country:** Korea, Republic of **Facility:** Chonnam National University Hwasun Hospital **Zip:** 58128 **Location 92:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Seoul National University Hospital **Zip:** 03080 **Location 93:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Severance Hospital, Yonsei University Health System **Zip:** 03722 **Location 94:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Asan Medical Center **Zip:** 05505 **Location 95:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Samsung Medical Center **Zip:** 06351 **Location 96:** **City:** Ulsan **Country:** Korea, Republic of **Facility:** Ulsan University Hosiptal **Zip:** 44033 **Location 97:** **City:** Gdansk **Country:** Poland **Facility:** Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii **Zip:** 80-219 **Location 98:** **City:** Myslowice **Country:** Poland **Facility:** ID Clinic **Zip:** 41-400 **Location 99:** **City:** Olsztyn **Country:** Poland **Facility:** SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY **Zip:** 10-228 **Location 100:** **City:** Warszawa **Country:** Poland **Facility:** Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy **Zip:** 02-781 **Location 101:** **City:** Wroc?aw **Country:** Poland **Facility:** Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii **Zip:** 53-413 **Location 102:** **City:** Moscow **Country:** Russian Federation **Facility:** FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies **State:** Moskovskaja Oblast **Zip:** 115478 **Location 103:** **City:** Saint Petersburg **Country:** Russian Federation **Facility:** GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology) **State:** Sankt Petersburg **Zip:** 197758 **Location 104:** **City:** Singapore **Country:** Singapore **Facility:** National Cancer Centre **Zip:** 169610 **Location 105:** **City:** Singapore **Country:** Singapore **Facility:** Tan Tock Seng Hospital; Oncology **Zip:** 308433 **Location 106:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Universitari Vall d'Hebron; Oncology **Zip:** 08035 **Location 107:** **City:** Madrid **Country:** Spain **Facility:** Hospital Clinico San Carlos; Servicio de Oncologia **Zip:** 28040 **Location 108:** **City:** Madrid **Country:** Spain **Facility:** Hospital Universitario La Paz; Servicio de Oncologia **Zip:** 28046 **Location 109:** **City:** Madrid **Country:** Spain **Facility:** Centro Integral Oncologico Clara Campal; Servicio de Oncología **Zip:** 28050 **Location 110:** **City:** Zaragoza **Country:** Spain **Facility:** Hospital Universitario Miguel Servet; Servicio de Oncologia Medica **Zip:** 50009 **Location 111:** **City:** Tainan **Country:** Taiwan **Facility:** National Cheng Kung University Hospital; Oncology **Zip:** 00704 **Location 112:** **City:** Tainan **Country:** Taiwan **Facility:** Chi-Mei Medical Centre; Hematology & Oncology **Zip:** 710 **Location 113:** **City:** Taipei **Country:** Taiwan **Facility:** Veterans General Hospital; Cancer Center **Zip:** 00112 **Location 114:** **City:** Taipei **Country:** Taiwan **Facility:** National Taiwan Uni Hospital; Dept of Oncology **Zip:** 100 **Location 115:** **City:** Taoyuan County **Country:** Taiwan **Facility:** Chang Gung Memorial Hospital-Linkou; Dept of Oncology **Zip:** 333 **Location 116:** **City:** Glasgow **Country:** United Kingdom **Facility:** Beatson West of Scotland Cancer Centre **Zip:** G12 0YN **Location 117:** **City:** London **Country:** United Kingdom **Facility:** Royal Free Hospital; Dept of Oncology **Zip:** NW3 2QG **Location 118:** **City:** London **Country:** United Kingdom **Facility:** King'S College Hospital **Zip:** SE5 9RS **Location 119:** **City:** Manchester **Country:** United Kingdom **Facility:** Christie Hospital Nhs Trust; Medical Oncology **Zip:** M2O 4BX #### Overall Officials **Official 1:** **Affiliation:** Hoffmann-La Roche **Name:** Clinical Trials **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). **IPD Sharing:** YES ### References Module #### References **Citation:** Kaseb AO, Guan Y, Gok Yavuz B, Abbas AR, Lu S, Hasanov E, Toh HC, Verret W, Wang Y. Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2022 Oct 11;9:1065-1079. doi: 10.2147/JHC.S369951. eCollection 2022. **PMID:** 36254201 **Citation:** Li Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022 Nov 15;128(22):3995-4003. doi: 10.1002/cncr.34457. Epub 2022 Sep 16. **PMID:** 36111952 **Citation:** Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11. **PMID:** 34902530 **Citation:** Salem R, Li D, Sommer N, Hernandez S, Verret W, Ding B, Lencioni R. Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial. Cancer Med. 2021 Aug;10(16):5437-5447. doi: 10.1002/cam4.4090. Epub 2021 Jun 29. **PMID:** 34189869 **Citation:** Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jul;22(7):991-1001. doi: 10.1016/S1470-2045(21)00151-0. Epub 2021 May 27. **PMID:** 34051880 **Citation:** Wen F, Zheng H, Zhang P, Liao W, Zhou K, Li Q. Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost-effectiveness analysis in China and the United states. Liver Int. 2021 May;41(5):1097-1104. doi: 10.1111/liv.14795. Epub 2021 Feb 8. **PMID:** 33556230 **Citation:** Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745. **PMID:** 32402160 ## Document Section ### Large Document Module #### Large Docs - Date: 2021-02-01 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1642772 - Type Abbrev: Prot - Upload Date: 2021-08-16T15:08 - Date: 2019-02-22 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 706880 - Type Abbrev: SAP - Upload Date: 2021-08-16T15:08 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000000230 - Term: Adenocarcinoma - ID: D000008113 - Term: Liver Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004066 - Term: Digestive System Diseases - ID: D000008107 - Term: Liver Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: HIGH - As Found: Carcinoma, Hepatocellular - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M11113 - Name: Liver Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000006528 - Term: Carcinoma, Hepatocellular ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000006131 - Term: Growth Inhibitors - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000082082 - Term: Immune Checkpoint Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M246 - Name: Bevacizumab - Relevance: HIGH - As Found: Non- - ID: M349417 - Name: Atezolizumab - Relevance: HIGH - As Found: Measured - ID: M1680 - Name: Sorafenib - Relevance: HIGH - As Found: Setting - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068258 - Term: Bevacizumab - ID: C000594389 - Term: Atezolizumab - ID: D000077157 - Term: Sorafenib ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2021-09-16 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** All-cause mortality is reported for deaths that occurred during the study based on the ITT population, which included all randomized participants. Serious and other adverse events were reported based on the safety population, which included all randomized participants who received any amount of study drug with participants grouped according to the treatment the participant actually received. Global and China extension periods were analyzed separately. #### Event Groups **Group ID:** EG000 **Title:** Sorafenib - Global **Deaths Num Affected:** 115 **Deaths Num At Risk:** 165 **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** EG000 **Other Num Affected:** 147 **Other Num at Risk:** 156 **Serious Number Affected:** 51 **Serious Number At Risk:** 156 **Title:** Sorafenib - Global **Group ID:** EG001 **Title:** Atezolizumab + Bevacizumab - Global **Deaths Num Affected:** 228 **Deaths Num At Risk:** 336 **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** EG001 **Other Num Affected:** 311 **Other Num at Risk:** 329 **Serious Number Affected:** 171 **Serious Number At Risk:** 329 **Title:** Atezolizumab + Bevacizumab - Global **Group ID:** EG002 **Title:** Sorafenib - China **Deaths Num Affected:** 46 **Deaths Num At Risk:** 61 **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** EG002 **Other Num Affected:** 55 **Other Num at Risk:** 58 **Serious Number Affected:** 12 **Serious Number At Risk:** 58 **Title:** Sorafenib - China **Group ID:** EG003 **Title:** Atezolizumab + Bevacizumab - China **Deaths Num Affected:** 88 **Deaths Num At Risk:** 133 **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** EG003 **Other Num Affected:** 129 **Other Num at Risk:** 132 **Serious Number Affected:** 54 **Serious Number At Risk:** 132 **Title:** Atezolizumab + Bevacizumab - China **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Leukopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hypothyroidism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal distension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Ascites **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Stomatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Asthenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Blood alkaline phosphatase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Blood bilirubin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Blood creatinine increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Platelet count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Weight decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** White blood cell count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hyperglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hypoalbuminaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hypophosphataemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Proteinuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Dysphonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Palmar-plantar erythrodysaesthesia syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hyperthyroidism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Gingival bleeding **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Malaise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hepatic function abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Bilirubin conjugated increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Blood bilirubin unconjugated increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Blood lactate dehydrogenase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Blood thyroid stimulating hormone increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Gamma-glutamyltransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Lymphocyte count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Protein urine present **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Prothrombin time prolonged **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 **Term:** Hypoproteinaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Cylindruria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Haematuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Haemoptysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Rash maculo-papular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 #### Serious Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 329 **Num Events:** 7 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 3 **Num At Risk:** 132 **Num Events:** 3 **Term:** Immune thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 4 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 58 **Num Events:** 2 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 3 **Term:** Acute coronary syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Atrial fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cardiac arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cardiac failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 329 **Num Events:** 4 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** Hydrocele **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypoacusis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Addison's disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypophysitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Blindness unilateral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Abdominal distension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** Anal fissure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Ascites **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 13 **Num At Risk:** 329 **Num Events:** 18 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 6 **Num At Risk:** 132 **Num Events:** 9 **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 329 **Num Events:** 5 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 329 **Num Events:** 5 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Duodenal ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Dysphagia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Gastric mucosal lesion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Gastric ulcer haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Gastric ulcer perforation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Gastric varices haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 329 **Num Events:** 4 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 156 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 11 **Num At Risk:** 329 **Num Events:** 11 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 3 **Num At Risk:** 132 **Num Events:** 3 **Term:** Gastrointestinal necrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Haematemesis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Haemoperitoneum **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hiatus hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Ileus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Immune-mediated enterocolitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Incarcerated umbilical hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Large intestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Melaena **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Mesenteric vein thrombosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Mouth haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Oesophageal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Oesophageal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Oesophageal varices haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 10 **Num At Risk:** 329 **Num Events:** 12 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 3 **Term:** Pancreatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Rectal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 5 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Umbilical hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Upper gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 329 **Num Events:** 5 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 5 **Num At Risk:** 132 **Num Events:** 5 **Term:** Varices oesophageal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** General physical health deterioration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Multiple organ dysfunction syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 11 **Num At Risk:** 329 **Num Events:** 15 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 4 **Num At Risk:** 132 **Num Events:** 7 **Term:** Acute hepatic failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Autoimmune hepatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Bile duct stone **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cholangitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 329 **Num Events:** 6 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cholecystitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Drug-induced liver injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatic cirrhosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatic failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 329 **Num Events:** 4 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatic function abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 5 **Num At Risk:** 132 **Num Events:** 5 **Term:** Hepatic pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatobiliary disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatorenal failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatorenal syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hyperbilirubinaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypertransaminasaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Jaundice **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Liver injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Anaphylactic reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cytokine release syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Abscess limb **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Biliary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Burkholderia pseudomallei infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Device related infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Empyema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Escherichia sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Haemophilus infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatitis E **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Herpes simplex encephalitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Lower respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Peritoneal abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Peritonitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Peritonsillar abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 329 **Num Events:** 5 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 3 **Num At Risk:** 132 **Num Events:** 3 **Term:** Post procedural infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 8 **Num At Risk:** 329 **Num Events:** 9 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Septic shock **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Skin infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Tooth infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Tuberculosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Urosepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Acetabulum fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Compression fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hip fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Humerus fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 329 **Num Events:** 6 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pelvic fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Spinal compression fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Amylase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 329 **Num Events:** 4 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Blood bilirubin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 329 **Num Events:** 7 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** General physical condition abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Granulocyte count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Lipase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Liver function test increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Platelet count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Diabetes mellitus inadequate control **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hyperammonaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hyperglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hyperglycaemic hyperosmolar nonketotic syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hyperkalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Hypoalbuminaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypoglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypoproteinaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Lactic acidosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Metabolic acidosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Type 2 diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Autoimmune arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Groin pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Muscular weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Myositis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pathological fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Tendonitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Chronic myeloid leukaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Gastric cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Neoplasm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Oesophageal squamous cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Tumour haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Tumour rupture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Altered state of consciousness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cerebral haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cerebral infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 132 **Num Events:** 2 **Term:** Encephalopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Epilepsy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Haemorrhage intracranial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hepatic encephalopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 156 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 329 **Num Events:** 6 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 2 **Term:** Metabolic encephalopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Subarachnoid haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Subdural hygroma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** VIth nerve disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** VIth nerve paralysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Confusional state **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Delirium **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Mental status changes **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 4 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Haematuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Nephritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Renal failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Renal haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pelvic pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Asthma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Chronic obstructive pulmonary disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Haemoptysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hiccups **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pleural effusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 5 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 2 **Term:** Pneumonitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Pneumothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pulmonary embolism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pulmonary haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pulmonary hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Respiratory distress **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Drug eruption **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Skin ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Toxic skin eruption **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Bleeding varicose vein **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Deep vein thrombosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Embolism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 329 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Phlebitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 156 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 329 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Thrombosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Hypersplenism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Bradycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Cardiac failure congestive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Cataract **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Diaphragmatic hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** COVID-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Peritonitis bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Pneumonia aspiration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Streptococcal bacteraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Subdural haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Toxicity to various agents **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Nephropathy toxic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Proteinuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 329 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Renal impairment **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Scrotal dermatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Acute pulmonary oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 132 **Term:** Orthopnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Cutaneous vasculitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Term:** Peripheral vascular disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 156 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 329 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 132 **Num Events:** 1 **Time Frame:** Up to end of study (up to approximately 56 months) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 183 **Group ID:** BG001 **Value:** 375 **Group ID:** BG002 **Value:** 558 **Units:** Participants ### Group **ID:** BG000 **Title:** Sorafenib - All **Description:** All participants either in the Global or China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. ### Group **ID:** BG001 **Title:** Atezolizumab + Bevacizumab - All **Description:** All participants either in the Global or China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10.9 **Value:** 64.4 #### Measurement **Group ID:** BG001 **Spread:** 11.9 **Value:** 62.9 #### Measurement **Group ID:** BG002 **Spread:** 11.6 **Value:** 63.4 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 165 **Group ID:** BG001 **Value:** 336 **Group ID:** BG002 **Value:** 501 **Class Title:** Global #### Measurement **Group ID:** BG000 **Spread:** 12.7 **Value:** 57.5 #### Measurement **Group ID:** BG001 **Spread:** 12.0 **Value:** 55.3 #### Measurement **Group ID:** BG002 **Spread:** 12.3 **Value:** 56.0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 61 **Group ID:** BG001 **Value:** 133 **Group ID:** BG002 **Value:** 194 **Class Title:** China ### Measure #### Measurement **Group ID:** BG000 **Value:** 28 #### Measurement **Group ID:** BG001 **Value:** 59 #### Measurement **Group ID:** BG002 **Value:** 87 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 137 #### Measurement **Group ID:** BG001 **Value:** 277 #### Measurement **Group ID:** BG002 **Value:** 414 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 165 **Group ID:** BG001 **Value:** 336 **Group ID:** BG002 **Value:** 501 **Class Title:** Global #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 17 #### Measurement **Group ID:** BG002 **Value:** 29 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 49 #### Measurement **Group ID:** BG001 **Value:** 116 #### Measurement **Group ID:** BG002 **Value:** 165 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 61 **Group ID:** BG001 **Value:** 133 **Group ID:** BG002 **Value:** 194 **Class Title:** China ### Measure #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 9 #### Measurement **Group ID:** BG002 **Value:** 13 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 149 #### Measurement **Group ID:** BG001 **Value:** 306 #### Measurement **Group ID:** BG002 **Value:** 455 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 21 #### Measurement **Group ID:** BG002 **Value:** 33 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 165 **Group ID:** BG001 **Value:** 336 **Group ID:** BG002 **Value:** 501 **Class Title:** Global #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 61 #### Measurement **Group ID:** BG001 **Value:** 133 #### Measurement **Group ID:** BG002 **Value:** 194 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 61 **Group ID:** BG001 **Value:** 133 **Group ID:** BG002 **Value:** 194 **Class Title:** China ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 96 #### Measurement **Group ID:** BG001 **Value:** 188 #### Measurement **Group ID:** BG002 **Value:** 284 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 10 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 52 #### Measurement **Group ID:** BG001 **Value:** 123 #### Measurement **Group ID:** BG002 **Value:** 175 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 19 #### Measurement **Group ID:** BG002 **Value:** 31 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 165 **Group ID:** BG001 **Value:** 336 **Group ID:** BG002 **Value:** 501 **Class Title:** Global #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 61 #### Measurement **Group ID:** BG001 **Value:** 133 #### Measurement **Group ID:** BG002 **Value:** 194 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 61 **Group ID:** BG001 **Value:** 133 **Group ID:** BG002 **Value:** 194 **Class Title:** China **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** The Global population included 501 participants. The China population included 57 participants enrolled during the China Extension plus 137 Chinese participants from the Global population. **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The Global population included 501 participants. The China population included 57 participants enrolled during the China Extension plus 137 Chinese participants from the Global population. **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The Global population included 501 participants. The China population included 57 participants enrolled during the China Extension plus 137 Chinese participants from the Global population. **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The Global population included 501 participants. The China population included 57 participants enrolled during the China Extension plus 137 Chinese participants from the Global population. **Title:** Race (NIH/OMB) **Unit of Measure:** Participants **Population Description:** The intent-to-treat (ITT) population included 558 participants (All) with 501 in the Global population. An additional 57 participants enrolled in the China Extension. The China population included 137 Chinese participants from the Global population plus 57 participants from the China Extension. The Global population and China population were analyzed separately. ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** genentech@druginfo.com **Organization:** Hoffmann-La Roche **Phone:** 800 821-8590 **Title:** Medical Communications ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.42 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.79 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** At CCOD 18 months; Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline alpha-fetoprotein (AFP: \<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0006 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.58 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.85 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** At CCOD 30 months; Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline alpha-fetoprotein (AFP: \<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0009 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.66 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 0.47 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.76 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.59 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 0.25 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.76 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** At CCOD 18 months; Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0026 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.44 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.35 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.80 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** At CCOD 30 months; Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0019 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.53 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** 0.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.90 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0117 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.60 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** 1.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.01 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 2.90 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 2.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.71 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 3.39 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** 2.99 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 12.66 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 6.15 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** 0.08 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.70 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0051 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.23 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** 0.12 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.73 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0048 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.30 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 10 #### Analysis **CI Lower Limit:** 0.16 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.15 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.4187 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.59 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 11 #### Analysis **CI Lower Limit:** 0.46 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.74 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.59 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 12 #### Analysis **CI Lower Limit:** 0.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.57 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.45 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 13 #### Analysis **CI Lower Limit:** 0.53 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.92 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0105 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.70 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 14 #### Analysis **CI Lower Limit:** 0.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.90 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0063 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.69 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 15 #### Analysis **CI Lower Limit:** 0.35 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.57 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.44 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 16 #### Analysis **CI Lower Limit:** 0.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.78 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** AFP \<400 ng/mL and stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0019 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.50 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.42 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.06 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** AFP \>/= 400 ng/mL and stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0879 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.67 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 17 #### Analysis **CI Lower Limit:** 0.37 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.68 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** AFP\<400 ng/mL and stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.50 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.53 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.15 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** AFP \>/=400 ng/mL and stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.2159 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.78 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 18 #### Analysis **CI Lower Limit:** 0.31 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.57 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** AFP \<400 ng/mL and stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.42 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.35 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.73 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** AFP \>/=400 ng/mL and stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.51 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 19 #### Analysis **CI Lower Limit:** 0.39 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.73 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Physical Functioning: Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.53 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.46 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.84 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Role Functioning: Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0019 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.62 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.46 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.85 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** GHS/QoL: Stratified by geographic region (Asia \[excluding Japan\] vs. rest of world), macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0028 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.63 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ### Outcome Measure 24 #### Analysis **CI Lower Limit:** 1.53 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.86 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0036 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 4.60 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 25 #### Analysis **CI Lower Limit:** 1.72 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 12.87 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0013 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 4.71 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 26 #### Analysis **CI Lower Limit:** 1.47 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 17.39 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0052 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 5.05 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 27 #### Analysis **CI Lower Limit:** 0.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.85 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.4581 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.37 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 28 #### Analysis **CI Lower Limit:** 0.01 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.91 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Lower limit: \<0.01 **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0100 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.08 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 29 #### Analysis **CI Lower Limit:** 0.03 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.69 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.3477 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.33 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 30 #### Analysis **CI Lower Limit:** 0.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.89 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0103 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.59 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 31 #### Analysis **CI Lower Limit:** 0.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.71 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.49 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 32 #### Analysis **CI Lower Limit:** 0.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.07 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0927 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.68 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 33 #### Analysis **CI Lower Limit:** 0.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.06 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0861 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.67 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 34 #### Analysis **CI Lower Limit:** 0.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.74 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0004 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.49 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 35 #### Analysis **CI Lower Limit:** 0.26 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.78 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Physical Functioning: Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0035 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.45 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.42 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.23 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Role Functioning: Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.2214 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.71 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.88 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** GHS/QoL: Stratified by macrovascular invasion and/or extrahepatic spread (presence vs. absence), and baseline AFP (\<400 vs. \>/= 400 ng/mL). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0135 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.53 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 36 ### Outcome Measure 37 ### Outcome Measure 38 ### Outcome Measure 39 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 10.41 - **Spread:** - **Upper Limit:** NA - **Value:** 13.24 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 11.37 - **Spread:** - **Upper Limit:** 16.85 - **Value:** 13.40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 17.02 - **Spread:** - **Upper Limit:** 23.66 - **Value:** 19.22 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.98 - **Spread:** - **Upper Limit:** 5.55 - **Value:** 4.27 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.75 - **Spread:** - **Upper Limit:** 8.28 - **Value:** 6.83 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 6.74 - **Spread:** - **Upper Limit:** NA - **Value:** 11.37 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 13.50 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.74 - **Spread:** - **Upper Limit:** 16.07 - **Value:** 11.37 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 17.12 - **Spread:** - **Upper Limit:** NA - **Value:** 24.05 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.56 - **Spread:** - **Upper Limit:** 4.76 - **Value:** 3.19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.17 - **Spread:** - **Upper Limit:** 8.28 - **Value:** 5.72 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7.35 - **Spread:** - **Upper Limit:** 18.03 - **Value:** 11.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 22.54 - **Spread:** - **Upper Limit:** 32.48 - **Value:** 27.3 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8.42 - **Spread:** - **Upper Limit:** 19.60 - **Value:** 13.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 28.13 - **Spread:** - **Upper Limit:** 38.64 - **Value:** 33.2 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.54 - **Spread:** - **Upper Limit:** 10.16 - **Value:** 5.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 21.01 - **Spread:** - **Upper Limit:** 30.61 - **Value:** 25.6 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 4.67 - **Spread:** - **Upper Limit:** NA - **Value:** 6.28 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 4.86 - **Spread:** - **Upper Limit:** NA - **Value:** 6.28 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 5.39 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 13.08 - **Spread:** - **Upper Limit:** NA - **Value:** 13.08 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.98 - **Spread:** - **Upper Limit:** 5.45 - **Value:** 4.24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.72 - **Spread:** - **Upper Limit:** 7.69 - **Value:** 6.83 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.76 - **Spread:** - **Upper Limit:** 4.17 - **Value:** 2.89 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.68 - **Spread:** - **Upper Limit:** 8.44 - **Value:** 7.06 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.21 - **Spread:** - **Upper Limit:** 7.72 - **Value:** 5.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.83 - **Spread:** - **Upper Limit:** 9.86 - **Value:** 8.57 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.21 - **Spread:** - **Upper Limit:** 7.69 - **Value:** 5.55 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.80 - **Spread:** - **Upper Limit:** 9.86 - **Value:** 8.28 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.83 - **Spread:** - **Upper Limit:** 4.30 - **Value:** 3.98 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.93 - **Spread:** - **Upper Limit:** 9.92 - **Value:** 8.54 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 11.73 - **Spread:** - **Upper Limit:** NA - **Value:** 13.93 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 104 - **Group ID:** OG001 - **Value:** 210 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 5.75 - **Spread:** - **Upper Limit:** NA - **Value:** 9.10 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 10.15 - **Spread:** - **Upper Limit:** NA - **Value:** 12.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 61 - **Group ID:** OG001 - **Value:** 126 **Units:** Participants #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.01 - **Spread:** - **Upper Limit:** 6.21 - **Value:** 4.40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.83 - **Spread:** - **Upper Limit:** 11.04 - **Value:** 8.28 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 104 - **Group ID:** OG001 - **Value:** 210 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.76 - **Spread:** - **Upper Limit:** 5.26 - **Value:** 4.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3.94 - **Spread:** - **Upper Limit:** 6.77 - **Value:** 5.19 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 61 - **Group ID:** OG001 - **Value:** 126 **Units:** Participants #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.79 - **Spread:** - **Upper Limit:** 5.62 - **Value:** 3.98 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.06 - **Spread:** - **Upper Limit:** 9.66 - **Value:** 8.41 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 104 - **Group ID:** OG001 - **Value:** 210 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.58 - **Spread:** - **Upper Limit:** 3.98 - **Value:** 2.79 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.17 - **Spread:** - **Upper Limit:** 6.90 - **Value:** 5.42 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 61 - **Group ID:** OG001 - **Value:** 126 **Units:** Participants #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.48 - **Spread:** - **Upper Limit:** 6.24 - **Value:** 4.86 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 9.69 - **Spread:** - **Upper Limit:** NA - **Value:** 13.14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.20 - **Spread:** - **Upper Limit:** 5.98 - **Value:** 3.58 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 6.51 - **Spread:** - **Upper Limit:** NA - **Value:** 9.13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.02 - **Spread:** - **Upper Limit:** 6.97 - **Value:** 3.58 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 5.98 - **Spread:** - **Upper Limit:** NA - **Value:** 11.24 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 154 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 322 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 132 - **Upper Limit:** - **Value:** 398 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 50.2 - **Upper Limit:** - **Value:** 79.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 298 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 55.4 - **Upper Limit:** - **Value:** 101 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 41 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 63.7 - **Upper Limit:** - **Value:** 131 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 263 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 61.7 - **Upper Limit:** - **Value:** 145 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 134 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 82.9 - **Upper Limit:** - **Value:** 168 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 153 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 65.0 - **Upper Limit:** - **Value:** 167 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 124 **Units:** Participants #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 316 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 318 **Units:** Participants #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.85 - **Spread:** - **Upper Limit:** 16.20 - **Value:** 6.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 17.49 - **Spread:** - **Upper Limit:** 32.94 - **Value:** 24.6 **Title:** #### Outcome Measure 25 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.81 - **Spread:** - **Upper Limit:** 18.68 - **Value:** 8.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 21.94 - **Spread:** - **Upper Limit:** 38.40 - **Value:** 29.7 **Title:** #### Outcome Measure 26 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.03 - **Spread:** - **Upper Limit:** 13.71 - **Value:** 4.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 14.47 - **Spread:** - **Upper Limit:** 28.97 - **Value:** 21.1 **Title:** #### Outcome Measure 27 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 4.86 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 8.15 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 28 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 4.47 - **Spread:** - **Upper Limit:** NA - **Value:** 4.86 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 8.15 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 29 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 4.17 - **Spread:** - **Upper Limit:** NA - **Value:** 5.55 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 30 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.56 - **Spread:** - **Upper Limit:** 4.76 - **Value:** 3.19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.17 - **Spread:** - **Upper Limit:** 8.11 - **Value:** 5.72 **Title:** #### Outcome Measure 31 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.73 - **Spread:** - **Upper Limit:** 3.98 - **Value:** 2.83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.21 - **Spread:** - **Upper Limit:** 8.34 - **Value:** 5.55 **Title:** #### Outcome Measure 32 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.76 - **Spread:** - **Upper Limit:** 10.15 - **Value:** 4.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.45 - **Spread:** - **Upper Limit:** 9.49 - **Value:** 7.00 **Title:** #### Outcome Measure 33 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.76 - **Spread:** - **Upper Limit:** 10.15 - **Value:** 4.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.45 - **Spread:** - **Upper Limit:** 9.49 - **Value:** 7.00 **Title:** #### Outcome Measure 34 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.79 - **Spread:** - **Upper Limit:** 4.17 - **Value:** 2.83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.32 - **Spread:** - **Upper Limit:** 9.33 - **Value:** 6.83 **Title:** #### Outcome Measure 35 **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 2.10 - **Spread:** - **Upper Limit:** NA - **Value:** 5.62 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 9.69 - **Spread:** - **Upper Limit:** NA - **Value:** 13.14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG000 - **Lower Limit:** 2.14 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 7.20 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.48 - **Spread:** - **Upper Limit:** 9.82 - **Value:** 3.58 - **Comment:** NA = not estimable due to the limited number of events observed - **Group ID:** OG001 - **Lower Limit:** 6.24 - **Spread:** - **Upper Limit:** NA - **Value:** 9.76 **Title:** #### Outcome Measure 36 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 131 **Title:** #### Outcome Measure 37 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 153 - **Upper Limit:** - **Value:** 456 **Title:** #### Outcome Measure 38 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 65.7 - **Upper Limit:** - **Value:** 92.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 87 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 36.8 - **Upper Limit:** - **Value:** 105 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 61.4 - **Upper Limit:** - **Value:** 143 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 80 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 61.9 - **Upper Limit:** - **Value:** 177 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 97.6 - **Upper Limit:** - **Value:** 201 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 79.4 - **Upper Limit:** - **Value:** 208 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 13 **Units:** Participants #### Outcome Measure 39 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 90 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 89 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** OS was defined as the time from randomization to death from any cause. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months) **Title:** Overall Survival (OS) in the Global Population **Type:** PRIMARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 2 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population **Type:** PRIMARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 3 **Description:** OS was defined as the time from randomization to death from any cause. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months) **Title:** Overall Survival (OS) in the China Population **Type:** PRIMARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 4 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS-IRF Per RECIST v1.1 in the China Population **Type:** PRIMARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 5 **Description:** ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Global ITT population with measurable disease at baseline consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment, and had measurable disease at baseline. **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 6 **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Global ITT population with measurable disease at baseline consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment, and had measurable disease at baseline. **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the Global Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 7 **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Global ITT population with measurable disease at baseline consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment, and had measurable disease at baseline. **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 8 **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The analysis population included Global participants with a confirmed response (CR or PR). **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 9 **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The analysis population included Global participants with a confirmed response (CR or PR). **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 10 **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The analysis population included Global participants with a confirmed response (CR or PR). **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 11 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS-IRF Per HCC mRECIST in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 12 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 13 **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 14 **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** TTP-IRF Per HCC mRECIST in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 15 **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 16 **Description:** OS was defined as the time from randomization to death from any cause. Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** From randomization to death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Overall Survival by Baseline AFP in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 17 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS-IRF Per RECIST v1.1 by Baseline AFP in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 18 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS-INV Per RECIST v1.1 by Baseline AFP in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 19 **Description:** TTD was defined as the time from randomization to the first deterioration (decrease from baseline of \>/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Global ITT population consisted of all randomized participants in the Global population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Time to Deterioration (TTD) in the Global Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 20 **Description:** An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Global safety population included all randomized Global participants who received any amount of study drug with participants grouped according to the treatment the participant actually received. **Reporting Status:** POSTED **Time Frame:** Up to end of study (up to approximately 56 months) **Title:** Number of Participants With Adverse Events (AEs) in the Global Population **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - Global ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 21 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The Global pharmacokinetic (PK)-evaluable population was defined as all participants in the Global population who received any dose of study treatment and who had at least one post-baseline PK sample available. **Reporting Status:** POSTED **Time Frame:** Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) **Title:** Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population **Type:** SECONDARY **Unit of Measure:** micrograms/milliliter (mcg/mL) ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 22 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The Global pharmacokinetic (PK)-evaluable population was defined as all participants in the Global population who received any dose of study treatment and who had at least one post-baseline PK sample available. **Reporting Status:** POSTED **Time Frame:** Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) **Title:** Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population **Type:** SECONDARY **Unit of Measure:** mcg/mL ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 23 **Parameter Type:** NUMBER **Population Description:** The Global ADA-evaluable population was defined as all participants in the Global population who received any dose of atezolizumab and who had at least one post-baseline ADA assessment. **Reporting Status:** POSTED **Time Frame:** Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 30 months) **Title:** Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 24 **Description:** ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** China ITT population with measurable disease at baseline consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment, and had measurable disease at baseline. **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 25 **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** China ITT population with measurable disease at baseline consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment, and had measurable disease at baseline. **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the China Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 26 **Description:** ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** China ITT population with measurable disease at baseline consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment, and had measurable disease at baseline. **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 27 **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The analysis population included China participants with a confirmed response (CR or PR). **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 28 **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The analysis population included China participants with a confirmed response (CR or PR). **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 29 **Description:** DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The analysis population included China participants with a confirmed response (CR or PR). **Reporting Status:** POSTED **Time Frame:** Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 30 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS-IRF Per HCC mRECIST in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 31 **Description:** PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 32 **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 33 **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** TTP-IRF Per HCC mRECIST in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 34 **Description:** Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 35 **Description:** TTD was defined as the time from randomization to the first deterioration (decrease from baseline of \>/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** China ITT population consisted of all randomized participants in the China population, whether or not the participant had received the assigned study treatment. **Reporting Status:** POSTED **Time Frame:** Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) **Title:** Time to Deterioration (TTD) in the China Population **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 36 **Description:** An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** China safety population included all randomized China participants who received any amount of study drug with participants grouped according to the treatment the participant actually received. **Reporting Status:** POSTED **Time Frame:** Up to end of study (up to approximately 56 months) **Title:** Number of Participants With Adverse Events (AEs) in the China Population **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Sorafenib - China ##### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG001 **Title:** Atezolizumab + Bevacizumab - Global #### Outcome Measure 37 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The China PK-evaluable population was defined as all participants in the China population who received any dose of study treatment and who had at least one post-baseline PK sample available. **Reporting Status:** POSTED **Time Frame:** Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) **Title:** Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population **Type:** SECONDARY **Unit of Measure:** mcg/mL ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 38 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The China PK-evaluable population was defined as all participants in the China population who received any dose of study treatment and who had at least one post-baseline PK sample available. **Reporting Status:** POSTED **Time Frame:** Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) **Title:** Trough Serum Concentration (Cmin) of Atezolizumab in the China Population **Type:** SECONDARY **Unit of Measure:** mcg/mL ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Atezolizumab + Bevacizumab - China #### Outcome Measure 39 **Parameter Type:** NUMBER **Population Description:** The China ADA-evaluable population was defined as all participants in the China population who received any dose of atezolizumab and who had at least one post-baseline ADA assessment. **Reporting Status:** POSTED **Time Frame:** Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 18 months) **Title:** Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** OG000 **Title:** Atezolizumab + Bevacizumab - China ### Participant Flow Module #### Group **Description:** Participants in the Global population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** FG000 **Title:** Sorafenib - Global #### Group **Description:** Participants in the Global population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** FG001 **Title:** Atezolizumab + Bevacizumab - Global #### Group **Description:** Participants in the China population received sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** FG002 **Title:** Sorafenib - China #### Group **Description:** Participants in the China population received Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. **ID:** FG003 **Title:** Atezolizumab + Bevacizumab - China #### Period **Title:** Global Period ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 115 ###### Reason **Group ID:** FG001 **Number of Subjects:** 228 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 20 ###### Reason **Group ID:** FG001 **Number of Subjects:** 21 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Reason Unspecified ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Study Ended by Sponsor ###### Reason **Group ID:** FG000 **Number of Subjects:** 26 ###### Reason **Group ID:** FG001 **Number of Subjects:** 80 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 165 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 336 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 165 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 336 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 #### Period **Title:** China Extension Period ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 3 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 46 ###### Reason **Group ID:** FG003 **Number of Subjects:** 88 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 8 ###### Reason **Group ID:** FG003 **Number of Subjects:** 6 ##### Withdraw **Type:** Study Ended by Sponsor ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 5 ###### Reason **Group ID:** FG003 **Number of Subjects:** 36 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 61 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 133 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 61 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 133 **Pre-Assignment Details:** The total study population included 558 participants. The Global population included 501 participants. An additional 57 participants enrolled during the China Extension. The total China population included 137 Chinese participants from the Global population plus 57 participants from the China extension. 137 participants were part of the Global as well as China populations. Separate analyses were performed for the Global population and the China population in the study. **Recruitment Details:** Participants were enrolled at 117 sites in 17 countries: Australia, Canada, China, Czech Republic, Germany, Spain, France, United Kingdom, Hong Kong, Italy, Japan, Republic of Korea, Poland, Russian Federation, Singapore, Taiwan, United States. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00005079 **Brief Title:** Timing of Menstrual Cycle and Surgery in Treating Premenopausal Women With Stage I, Stage II, or Stage III Breast Cancer **Official Title:** Timing of Breast Cancer Surgery, Menstrual Cycle and Prognosis #### Organization Study ID Info **ID:** UCLA-9810046 #### Organization **Class:** NIH **Full Name:** National Cancer Institute (NCI) #### Secondary ID Infos **Domain:** PDQ (Physician Data Query) **ID:** CDR0000067686 **Type:** REGISTRY **ID:** UCSD-985772 **ID:** NCI-G00-1724 ### Status Module #### Completion Date **Date:** 2004-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-05-15 **Type:** ESTIMATED **Last Update Submit Date:** 2013-05-14 **Overall Status:** COMPLETED #### Start Date **Date:** 1999-01 **Status Verified Date:** 2003-04 #### Study First Post Date **Date:** 2003-01-27 **Type:** ESTIMATED **Study First Submit Date:** 2000-04-06 **Study First Submit QC Date:** 2003-01-26 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** Jonsson Comprehensive Cancer Center ### Description Module **Brief Summary:** RATIONALE: The timing of breast cancer surgery within the menstrual cycle may affect outcome. It is not yet known if treatment is more effective during the initial or final phase of the menstrual cycle. PURPOSE: Phase III trial to determine the effect of menstrual cycle phase at surgery in treating premenopausal women who have stage I, stage II, or stage III breast cancer. **Detailed Description:** OBJECTIVES: * Determine if the timing of breast surgery during the menstrual cycle impacts disease recurrence, progression, or death among different racial groups in premenopausal women with stage I, II, or III breast cancer. * Determine if definitive breast cancer surgeries (e.g., lumpectomy or mastectomy) performed during the follicular phase result in poorer prognosis (recurrence, disease progression, or death) compared with surgeries performed during the midcycle or luteal phases in this patient population. OUTLINE: This is a multicenter study. Patients undergo either fine needle aspiration concurrently with definitive breast surgery (mastectomy or lumpectomy) or needle-directed excisional biopsy followed by definitive breast surgery. Patients undergo serum collection for hormonal analysis preoperatively, 24 hours post operatively, at days 7 and 14, and at 3 months and urine collection for hormonal analysis beginning 24 hours prior to surgery and continuing daily until the onset of the next menses. Patients complete a 30-minute telephone interview regarding medical, family, occupational, and reproductive history and lifestyle habits (e.g., diet, exercise, or environmental exposures). Beginning 24 hours prior to surgery and continuing until the onset of the next menses, patients complete a menstrual cycle journal indicating the start and length of menses. Patients undergoing mastectomy are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. Patients undergoing adjuvant therapy are followed every 3 months for 3 years and then every 6 months thereafter or every 4 months for 2 years and then every 6 months thereafter. PROJECTED ACCRUAL: Approximately 400 patients will be accrued for this study within 2.5 years. ### Conditions Module **Conditions:** - Breast Cancer **Keywords:** - stage I breast cancer - stage II breast cancer - stage IIIA breast cancer - stage IIIB breast cancer ### Design Module #### Design Info **Primary Purpose:** TREATMENT **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** conventional surgery **Type:** PROCEDURE ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: * Histologically confirmed stage I, II, or III primary breast cancer undergoing breast surgery * Invasive disease (e.g., lobular or ductal) * No bilateral disease * No distant metastases * Premenopausal * Regular menses (no amenorrhea of more than 90 days) without hormone replacement * Documented last menstrual period * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age: * Premenopausal Sex: * Female Menopausal status: * See Disease Characteristics Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified Other: * No other prior malignancies * Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No preoperative chemotherapy Endocrine therapy: * No concurrent hormonal replacement therapy * No concurrent interruptive oral contraceptive use of less than 3 months Radiotherapy: * Not specified Surgery: * See Disease Characteristics * No prior hysterectomy and/or bilateral oophorectomy **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** La Jolla **Country:** United States **Facility:** Rebecca and John Moores UCSD Cancer Center **State:** California **Zip:** 92093-0658 **Location 2:** **City:** Los Angeles **Country:** United States **Facility:** Jonsson Comprehensive Cancer Center, UCLA **State:** California **Zip:** 90095-1781 #### Overall Officials **Official 1:** **Affiliation:** Jonsson Comprehensive Cancer Center **Name:** Helena R. Chang, MD, PhD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02278679 **Acronym:** DiRECT **Brief Title:** Digital Rectal Exam Proficiency Tool **Official Title:** Validation of the DiRECT Proficiency Tool #### Organization Study ID Info **ID:** 17658 #### Organization **Class:** OTHER **Full Name:** University of Virginia ### Status Module #### Completion Date **Date:** 2018-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2017-05-18 **Type:** ACTUAL **Last Update Submit Date:** 2017-05-17 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-12 **Type:** ESTIMATED #### Start Date **Date:** 2014-10 **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2014-10-30 **Type:** ESTIMATED **Study First Submit Date:** 2014-10-28 **Study First Submit QC Date:** 2014-10-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Virginia #### Responsible Party **Investigator Affiliation:** University of Virginia **Investigator Full Name:** Tracey Krupski, MD **Investigator Title:** M.D. Associate Professor of Urology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A digital rectal exam proficiency tool, titled the 'DiRECT' was developed based on the consensus of 10 experts. The purpose of this study is to validate this tool for use in both undergraduate and graduate medical education . **Detailed Description:** First, it will be validated on 120 anesthetized patients undergoing prostate surgery, comparing responses on the digital rectal exam clinical tool (DiRECT) from both expert and novice clinicians, with surgical pathology reports. The second phase of validation will involve the participation of standardized patients, medical students and MUTA (medical urology teaching associate). During a standardized patient exercise focusing on digital rectal exam in the University of Virginia School of Medicine curriculum, 160 second-year medical students will be given the DiRECT to document their examination. An attending physician will also attend the standardized patient exercise and document their examination for comparison with the medical students. The third phase includes 8 residents and up to10 attendings in the Urology clinic, who will independently complete the DiRECT documenting their DRE in the course of usual care. Comparison of faculty and student/trainee responses in all phases will be used for validation of the clinical tool for further use in medical education. ### Conditions Module **Conditions:** - Prostatic Hyperplasia - Prostate Cancer ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 410 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** First, it will be validated on 120 anesthetized patients undergoing prostate surgery comparing responses on the digital rectal exam clinical tool (DiRECT) from both expert and novice clinicians, with surgical pathology reports. **Intervention Names:** - Procedure: Digital Rectal Exam **Label:** Anesthitized patient #### Arm Group 2 **Description:** During a standardized patient exercise focusing on digital rectal exam in the University of Virginia School of Medicine curriculum, 160 second-year medical students will be given the DiRECT to document their examination. An attending physician will also attend the standardized patient exercise and document their examination for comparison with the medical students. **Label:** Standardized patients #### Arm Group 3 **Description:** The third phase includes 8 residents and up to10 attendings in the Urology clinic, who will independently complete the DiRECT documenting their DRE in the course of usual care. **Label:** Clinic patient ### Interventions #### Intervention 1 **Arm Group Labels:** - Anesthitized patient **Description:** The DRE digital rectal exam is an essential component of physical examination, but physicians enter their residency having neither been appropriately exposed nor trained in performing DREs. , the attending physician, resident physician(s), and medical student(s) will each perform a digital rectal exam on the subject, and independently document their examination on the DiRECT instrument. **Name:** Digital Rectal Exam **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Validate DiRECT tool **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Subjects who are patients: * Patients who are male and adults ≥ 30 years of age * Standardized patients between the ages of 30-80 years participating in the University of Virginia School of Medicine activity for second-year students learning digital rectal exams Subjects who are clinicians: • Attending physician, resident physician, or medical student scrubbed in for a prostatectomy or cystectomy, seeing patients in urology clinic, or participating in the School of Medicine activity for second year students learning digital rectal exams Exclusion Criteria: List the criteria for exclusion * Patients who do not have a prostate * Patients with previous pelvic/perineal surgery * Previously enrolled in this study **Maximum Age:** 90 Years **Minimum Age:** 30 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects with Benign Prostate Hypertrophy, Prostate Cancer or routine digital exam being seen by Urology Attendings, residents or medical students. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** tlk6t@virginia.edu **Name:** Tracey L Krupski, M.D. **Phone:** 434-924-0042 **Role:** CONTACT #### Locations **Location 1:** **City:** Charlottesville **Contacts:** ***Contact 1:*** - **Email:** tlk6t@virginia.edu - **Name:** Tracey L Krupski, M.D. - **Phone:** 434-924-0042 - **Role:** CONTACT ***Contact 2:*** - **Email:** pya@virginia.edu - **Name:** Patricia Battle, LPN, CRC - **Phone:** 434-924-5649 - **Role:** CONTACT **Country:** United States **Facility:** University of Virginia Health System, Dept of Urology **State:** Virginia **Status:** RECRUITING **Zip:** 22908 #### Overall Officials **Official 1:** **Affiliation:** University of Virginia, Dept of Urology **Name:** Tracey L Krupski, M.D. **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Virginia, Dept of Urology **Name:** Raymond A Costabile, M.D. **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000011469 - Term: Prostatic Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M14334 - Name: Prostatic Hyperplasia - Relevance: HIGH - As Found: Prostatic Hyperplasia - ID: M10016 - Name: Hyperplasia - Relevance: HIGH - As Found: Hyperplasia - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011470 - Term: Prostatic Hyperplasia - ID: D000006965 - Term: Hyperplasia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01741779 **Brief Title:** Diet and Whole-body Vibration Training on Cardiovascular and Autonomic Function **Official Title:** The Effect of Diet and Whole-body Vibration Training on Cardiovascular and Autonomic Function in Obese Postmenopausal Women #### Organization Study ID Info **ID:** HSC2011.6728 #### Organization **Class:** OTHER **Full Name:** Florida State University ### Status Module #### Completion Date **Date:** 2012-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-12-05 **Type:** ESTIMATED **Last Update Submit Date:** 2012-12-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-04 **Type:** ACTUAL #### Start Date **Date:** 2011-09 **Status Verified Date:** 2012-12 #### Study First Post Date **Date:** 2012-12-05 **Type:** ESTIMATED **Study First Submit Date:** 2012-12-03 **Study First Submit QC Date:** 2012-12-03 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Nutrisystem, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Florida State University #### Responsible Party **Investigator Affiliation:** Florida State University **Investigator Full Name:** Arturo Figueroa **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Obesity is a major risk factor for premature arterial abnormalities including high blood pressure and increased stiffness. Previous studies have shown that weight loss via lifestyle modifications is associated with a decrease in large artery (aorta) stiffness. However, along with decreases in fat mass, hypocaloric diet reduces muscle mass. Whole body vibration results in similar increases in muscle mass and strength than those observed after resistance exercise and is feasible for special populations such as the obese and the elderly. The investigators hypothesis is that weight loss via diet combined with whole body vibration training would additively reduce arterial stiffness and blood pressure in obese women. The investigators also hypothesize that the improved arterial function with weight loss would be associated with beneficial changes in the main mechanisms involved in BP regulation. **Detailed Description:** The purpose of the study is to examine the effects of 12 weeks of whole body vibration training (WBVT) and diet on arterial function, autonomic function, and body composition in obese women. Specific aims of the study are to: To evaluate the extent to which diet and (WBVT) will improve body composition assessed by changes in fat mass and lean mass using dual-energy x-ray absorptiometry and waist circumference. To investigate that combined diet and (WBVT) are more efficacious than either treatment alone in ameliorating cardiovascular disease risk factors by assessing arterial stiffness (aortic, systemic, and leg), aortic BP and wave reflection, and autonomic function (heart rate variability, vascular sympathetic activity \[low-frequency power of systolic BP variability\], and baroreflex sensitivity). Flow mediated dilation and circulating levels of adipocytokines (adiponectin and leptin) and endothelial-derived vasodilators (NO metabolites \[NOx\], 6-keto PGFIa, insulin, and ghrelin) and vasoconstrictors (endothelin-1 \[ET-1\],8-iso PGF2a,vascular endothelium growth factor \[VGEF\]) will be assessed as secondary outcome variables. ### Conditions Module **Conditions:** - Obesity - Pre-hypertension - Hypertension **Keywords:** - whole body vibration training - hypocaloric diet - prehypertension - hypertension - obesity - arterial function - arterial stiffness - pulse wave velocity - autonomic function - endothelial function - adipocytokines ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This arm involves 12 wk of the standard Nutrisystem foods plan complemented by fresh produce and dairy. Subjects consume breakfast, lunch, dinner, and one (women) or two (men) snacks per day. **Intervention Names:** - Other: Hypocaloric diet **Label:** Hypocaloric diet **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This arm involves not making any change to the subject's lifestyle at the moment of the start of the intervention and for 12 wk. **Label:** Control **Type:** NO_INTERVENTION #### Arm Group 3 **Description:** Lower-body exercise training on a vibration platform and diet **Intervention Names:** - Other: Whole body vibration training & diet **Label:** Whole body vibration training & diet **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Lower-body exercises 3 times per wk for 12 wk in a vibration platform **Intervention Names:** - Other: Whole Body Vibration Training **Label:** Whole body vibration training **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Whole body vibration training **Description:** The Whole body vibration training intervention consists of lower-body exercise in a vibration platform 3 times per wk for 12 wk. The subjects will perform static and dynamic exercises for the legs on the vibration platform. Dynamic exercises will be performed with slow controlled movements starting from an upright position into a 60 degree knee flexion (squat) and maximal heel elevation (toestand). Static exercises will be performed without movement in the joint angles described previously. The training volume will increase progressively over the 12-week training period by increasing the intensity of vibration, duration of the exercise set (30-60 sec), number of sets per exercise, and total duration of the training session, and decreasing the duration of rest periods (30-60 sec).The intensity of vibration and amplitude will also be increased progressively (25-30 Hz of frequency and from low to high amplitude). **Name:** Whole Body Vibration Training **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Hypocaloric diet **Description:** The hypocaloric diet intervention consists of 12 wk of the standard Nutrisystem foods plan complemented by fresh produce and dairy. Subjects consume breakfast, lunch, dinner, and one (women) or two (men) snacks per day. **Name:** Hypocaloric diet **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Whole body vibration training & diet **Description:** Combination of whole body vibration training and hypocaloric diet **Name:** Whole body vibration training & diet **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** By measuring fat mass and lean soft tissue mass from dual-energy x-ray absorptiometry and waist circumference **Measure:** Body Composition **Time Frame:** 12 weeks **Description:** Non-invasive measures of brachial and aortic blood pressure **Measure:** Blood pressure **Time Frame:** 12 weeks **Description:** Using pulse wave velocity of the aorta, systemic, and legs **Measure:** Arterial Stiffness **Time Frame:** 12 weeks **Description:** Using the augmentation index from radial tonometry **Measure:** Pressure Wave Reflection **Time Frame:** 12 weeks **Description:** Heart rate variability, vascular sympathetic activity \[low-frequency power of systolic BP variability\], and spontaneous baroreflex sensitivity will be assessed from electrocardiogram and beat-by-beat digital blood pressure **Measure:** Autonomic Function **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** By measuring circulating levels of adipocytokines (adiponectin and leptin) and endothelial-derived vasodilators (NOx, 6-keto PGFIa, insulin, and ghrelin)and vasoconstrictors (ET-1 and 8-iso PGF2a, VEGF) **Measure:** Endothelial Function **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Female * 45 to 65 years of age * At least 1 year after menopause * Body mass index of 27-39.9 * Sedentary or low active (less than 2 hr per wk) Exclusion Criteria: * Younger than 45 or older than 65 years of age * Body mass index lower than 27, or 40 or higher * Physically active or competitively active * Smoker * Use of hormone replacement therapy of less than 1 yr * Use of calcium channel blocker or beta blockers * Use dietary supplementations (e.g.,L-arginine,L-citrulline,antioxidants) * Uncontrolled diabetes * Any restriction that would significantly interfere with compliance with the diet (e.g., allergy to nuts or dairy, or need to avoid soy) **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 45 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tallahassee **Country:** United States **Facility:** Florida State University **State:** Florida **Zip:** 32306 #### Overall Officials **Official 1:** **Affiliation:** Florida State University **Name:** Arturo Figueroa, M.D., Ph.D **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M29007 - Name: Prehypertension - Relevance: HIGH - As Found: Pre-hypertension - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006973 - Term: Hypertension - ID: D000058246 - Term: Prehypertension ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02409979 **Brief Title:** Impact of Carbon Dioxide Insufflation and Water Exchange on Post-Colonoscopy Outcomes **Official Title:** Impact of Carbon Dioxide Insufflation and Water Exchange on Post-Colonoscopy Outcomes: A Randomized Controlled Trial #### Organization Study ID Info **ID:** PG.2015/3645 #### Organization **Class:** OTHER **Full Name:** Presidio Ospedaliero Santa Barbara #### Secondary ID Infos **Domain:** Azienda USL 07 Carbonia, Regione Sardegna **ID:** Delibera 387/C 17 Marzo 2015 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2015-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-11-05 **Type:** ESTIMATED **Last Update Submit Date:** 2015-11-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-11 **Type:** ACTUAL #### Start Date **Date:** 2015-04 **Status Verified Date:** 2015-10 #### Study First Post Date **Date:** 2015-04-07 **Type:** ESTIMATED **Study First Submit Date:** 2015-03-23 **Study First Submit QC Date:** 2015-04-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Presidio Ospedaliero Santa Barbara #### Responsible Party **Investigator Affiliation:** Presidio Ospedaliero Santa Barbara **Investigator Full Name:** Sergio Cadoni, M.D. **Investigator Title:** Responsabile Servizio Endoscopia Digestiva **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Room air insufflated during colonoscopy cannot be completely suctioned, is not easily absorbed and remains in the bowel for quite some time, resulting in prolonged bowel distension with the discomfort of bloating. Sufferers often experience a sensation of fullness and abdominal pressure, relieved only after expulsion of the residual gas, often accompanied by colic pain. This can be a lengthy process, and some patients continue to report pain as long as 24 hours after the procedure. Abdominal discomfort after colonoscopy is an adverse event commonly reported by patients, and definitely associated with the procedure. Published reports show that the use of carbon dioxide (CO2) insufflation significantly decreases bloating and pain up to 24 hours post-procedure. Preliminary results of the investigators' previous study about on-demand sedation colonoscopy in diagnostic patients showed that, compared with CO2 insufflation, the water exchange group (WE, infusion of water to distend the lumen during insertion; suction of infused water, residual air pockets an feces predominantly during insertion) achieved significantly lower real-time insertion pain scores. Moreover (insertion-withdrawal method) WE-CO2 had the lowest bloating scores just after the procedure and at discharge, comparable with those achieved by CO2-CO2. Compared with WE-CO2, the use of WE-air insufflation (AI) showed significantly higher bloating scores just after the procedure and at discharge; compared with CO2-CO2 differences were significant only at discharge. The investigators decided to conduct a prospective randomized controlled trial comparing WE-CO2, WE-AI and CO2-CO2. The investigators will test the hypothesis that patients examined by the combination of WE-CO2 will have significantly lower bloating scores at specific time points after colonoscopy than those examined using WE-AI or CO2-CO2. The investigators will also assess the impact of these three methods on patients comfort and activities in the post-procedure period. **Detailed Description:** Design: Prospective double blinded two-center randomized controlled trial. Methods: Colonoscopy with CO2 insufflation and water exchange-CO2, water exchange-AI; split-dose bowel preparation; on demand-sedation. Control method: CO2 insufflation colonoscopy. Study methods: water exchange-CO2 colonoscopy, water exchange-AI colonoscopy. Population: Consecutive 18 to 80 year-old first-time diagnostic outpatients. After informed consent, assignment to control or study arms based on computer generated randomization list with block allocation and stratification. ### Conditions Module **Conditions:** - Abdominal Pain **Keywords:** - colonoscopy - carbon dioxide - water exchange - discomfort - colonoscopy pain ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR #### Enrollment Info **Count:** 246 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Colonoscopy performed as usual, with the minimal CO2 insufflation required to aid insertion and adequate distension during withdrawal for exploration. Washing allowed as needed. Considered to be standard procedure. **Intervention Names:** - Other: Carbon dioxide method **Label:** Carbon dioxide method **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Insufflation not used until the cecum is reached. Infusion of a sufficient amount of water to render the lumen a slit to progress with the colonoscope. Part of the infused water will be constantly suctioned back exchanging clean for opaque water. Air pockets and residual feces will be always aspirated. Withdrawal phase done using carbon dioxide insufflation. **Intervention Names:** - Other: Water Exchange-CO2 **Label:** Water Exchange-CO2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Insufflation not used until the cecum is reached. Infusion of a sufficient amount of water to render the lumen a slit to progress with the colonoscope. Part of the infused water will be constantly suctioned back exchanging clean for opaque water. Air pockets and residual feces will be always aspirated. Withdrawal phase done using air insufflation. **Intervention Names:** - Other: Water Exchange-AI **Label:** Water Exchange-AI **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Carbon dioxide method **Description:** Insufflation with CO2 during insertion and withdrawal phases of colonoscopy. **Name:** Carbon dioxide method **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Water Exchange-CO2 **Description:** Insertion using water exchange, withdrawal using CO2 insufflation. **Name:** Water Exchange-CO2 **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Water Exchange-AI **Description:** Insertion using water exchange, withdrawal using air insufflation. **Name:** Water Exchange-AI **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Cecal intubation will be defined as reaching beyond the ileocecal valve with adequate visualization of the appendix orifice. **Measure:** Cecal intubation rate. **Time Frame:** 1 hour. **Description:** Defined as the time for passage of the colonoscope from the rectum to the cecum. **Measure:** Cecal intubation time. **Time Frame:** 1 hour. **Description:** Total procedure time (including time required for water infusion, polyp resection or biopsy). **Measure:** Total procedure time. **Time Frame:** 1 hour. **Description:** Proportion of subjects with at least one adenoma of any size. **Measure:** Adenoma detection rate. **Time Frame:** 9 months. **Description:** Offered at patient request for a NRS score ≥2. Medications given as per institutional regulation. Dose titrated based on patients' reported real-time pain score, age, weight and comorbidity. **Measure:** On-demand sedation. **Time Frame:** 1 hour. **Description:** Significant oxygen desaturation (\<85% for \>15 seconds) will be recorded. **Measure:** Oxygen desaturation. **Time Frame:** 1 hour. **Description:** Vagal reaction (heart rate \<60 beats per minute accompanied by excessive sweating, nausea and/or vomiting) will be recorded. **Measure:** Vagal reaction. **Time Frame:** 1 hour. #### Primary Outcomes **Description:** Change of patients' sensation of abdominal bloating. Assessed by blinded observer just after examination, at discharge; and at 1, 3, 6, 12 and 24 hours after the procedure using a questionnaire given to patients. Measured on an eleven-point Numeric Rating Scale (NRS): 0=none, 10=full bloating. Results will be recorded by telephone recall. **Measure:** Change in abdominal bloating sensation after colonoscopy. **Time Frame:** Within the first 24 hours after the procedure. #### Secondary Outcomes **Description:** Assessed by blinded observer just after examination, at discharge; and at 1, 3, 6, 12 and 24 hours after the procedure using a questionnaire given to patients. Measured using an eleven-point NRS (0=none, 10=maximum pain). Results will be recorded by telephone recall. **Measure:** Change in pain score after colonoscopy. **Time Frame:** Within the first 24 hours after the procedure. **Description:** Pain assessed using a NRS (0=absence of pain, 2=simply "discomfort", 10=worst pain). Before the procedure, an endoscopic nurse will explain the NRS scoring system to the patients. At irregular intervals during colonoscopy (around 60 seconds) assisting nurse will ask patients about discomfort or pain. The responses will be recorded, and the maximum pain score noted. Colonoscopists not participating in gathering the informations. **Measure:** Real-time insertion pain. **Time Frame:** 1 hour. **Description:** Recorded at discharge and assessed post-procedure up to 6 hours using a questionnaire given to patients. Results will be recorded by telephone recall. **Measure:** Number of episodes of incontinence or of soiled underwear experienced in the 6 hours after colonoscopy. **Time Frame:** 6 hours. **Description:** Recorded at discharge and assessed post-procedure up to 24 hours using a questionnaire given to patients. Results will be recorded by telephone recall. **Measure:** Number of flatus episodes post-procedure. **Time Frame:** 24 hours. **Description:** Recorded at discharge and assessed post-procedure up to 6 hours using a questionnaire given to patients. Results will be recorded by telephone recall. **Measure:** Number of incontinence episodes post-procedure. **Time Frame:** 6 hours. **Description:** Recorded at discharge and assessed post-procedure up to 6 hours using a questionnaire given to patients. Results will be recorded by telephone recall. **Measure:** Toilet use for bowel movement post-procedure. **Time Frame:** 6 hours. **Description:** Assessed post-procedure after 24 hours using a questionnaire given to patients (0=not satisfied, 10=very satisfied). Results will be recorded by telephone recall. **Measure:** Patients' satisfaction with the procedure. **Time Frame:** 24 hours. **Description:** Assessed post-procedure after 24 hours using a questionnaire given to patients (0=not willing to repeat, 10=very likely to repeat). Results will be recorded by telephone recall. **Measure:** Willingness to repeat colonoscopy. **Time Frame:** 24 hours. **Description:** Assessed post-procedure after 12 hours using a questionnaire given to patients (0=nothing at all, 10=a lot). Results will be recorded by telephone recall. **Measure:** Interference of colonoscopy on work/normal activities the same day of the procedure. **Time Frame:** Up to 12 hours. **Description:** Work activities missed the day after colonoscopy due to some effect of the procedure (yes, no). Assessed post-procedure after 24 hours using a questionnaire given to patients. Results will be recorded by telephone recall. **Measure:** Day of work missed the day after the procedure. **Time Frame:** 24 hours. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * consecutive 18 to 80 year-old first-time diagnostic outpatients agreeing to start procedure without premedication Exclusion Criteria: * patient unwillingness to start the procedure without sedation/analgesia * previous colorectal surgery * proctosigmoidoscopy or bidirectional endoscopy * patient refusal or inability to provide informed consent * inadequate consumption of bowel preparation * moderate or severe chronic obstructive pulmonary disease requiring oxygen * medical history of CO2 retention * history of inflammatory bowel disease **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Los Angeles **Country:** United States **Facility:** Sepulveda Ambulatory Care Center, VA Greater Los Angeles Healthcare System **State:** California **Zip:** 91343 **Location 2:** **City:** Ostrava **Country:** Czech Republic **Facility:** Digestive Diseases Center, Vìtkovice Hospital **Zip:** 703 84 **Location 3:** **City:** Iglesias **Country:** Italy **Facility:** Digestive Endoscopy Unit, Ospedale S. Barbara **State:** CI **Zip:** 09016 #### Overall Officials **Official 1:** **Affiliation:** S. Barbara Hospital, Iglesias (CI) Italy **Name:** Sergio Cadoni, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Sumanac K, Zealley I, Fox BM, Rawlinson J, Salena B, Marshall JK, Stevenson GW, Hunt RH. Minimizing postcolonoscopy abdominal pain by using CO(2) insufflation: a prospective, randomized, double blind, controlled trial evaluating a new commercially available CO(2) delivery system. Gastrointest Endosc. 2002 Aug;56(2):190-4. doi: 10.1016/s0016-5107(02)70176-4. **PMID:** 12145595 **Citation:** Zubarik R, Fleischer DE, Mastropietro C, Lopez J, Carroll J, Benjamin S, Eisen G. Prospective analysis of complications 30 days after outpatient colonoscopy. Gastrointest Endosc. 1999 Sep;50(3):322-8. doi: 10.1053/ge.1999.v50.97111. **PMID:** 10462650 **Citation:** de Jonge V, Sint Nicolaas J, van Baalen O, Brouwer JT, Stolk MF, Tang TJ, van Tilburg AJ, van Leerdam ME, Kuipers EJ; SCoPE consortium. The incidence of 30-day adverse events after colonoscopy among outpatients in the Netherlands. Am J Gastroenterol. 2012 Jun;107(6):878-84. doi: 10.1038/ajg.2012.40. Epub 2012 Mar 6. **PMID:** 22391645 **Citation:** Lee YC, Wang HP, Chiu HM, Lin CP, Huang SP, Lai YP, Wu MS, Chen MF, Lin JT. Factors determining post-colonoscopy abdominal pain: prospective study of screening colonoscopy in 1000 subjects. J Gastroenterol Hepatol. 2006 Oct;21(10):1575-80. doi: 10.1111/j.1440-1746.2006.04145.x. **PMID:** 16928219 **Citation:** Falt P, Liberda M, Smajstrla V, Kliment M, Bartkova A, Tvrdik J, Fojtik P, Urban O. Combination of water immersion and carbon dioxide insufflation for minimal sedation colonoscopy: a prospective, randomized, single-center trial. Eur J Gastroenterol Hepatol. 2012 Aug;24(8):971-7. doi: 10.1097/MEG.0b013e3283543f16. **PMID:** 22569079 **Citation:** Cadoni S, Falt P, Gallittu P, Liggi M, Smajstrla V, Leung FW. Impact of carbon dioxide insufflation and water exchange on postcolonoscopy outcomes in patients receiving on-demand sedation: a randomized controlled trial. Gastrointest Endosc. 2017 Jan;85(1):210-218.e1. doi: 10.1016/j.gie.2016.05.021. Epub 2016 May 17. **PMID:** 27207825 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000012817 - Term: Signs and Symptoms, Digestive ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M18311 - Name: Abdominal Pain - Relevance: HIGH - As Found: Abdominal Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M15622 - Name: Signs and Symptoms, Digestive - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015746 - Term: Abdominal Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06228079 **Brief Title:** Adjuvant vs Surgery Only in Early-stage Recurrent NPC **Official Title:** Adjuvant Therapy Versus Endoscopic Surgery Alone in Early-stage Recurrent Nasopharyngeal Carcinoma: A Multicenter Randomized Controlled Trial #### Organization Study ID Info **ID:** early-rNPC-RCT-adj #### Organization **Class:** OTHER **Full Name:** Eye & ENT Hospital of Fudan University ### Status Module #### Completion Date **Date:** 2028-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-18 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2028-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-02-01 **Type:** ESTIMATED **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2024-01-29 **Type:** ACTUAL **Study First Submit Date:** 2023-12-21 **Study First Submit QC Date:** 2024-01-18 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Shanghai Zhongshan Hospital **Class:** OTHER **Name:** Shanghai 6th People's Hospital **Class:** OTHER **Name:** Changhai Hospital **Class:** OTHER **Name:** Fujian Medical University Union Hospital **Class:** OTHER **Name:** People's Hospital of Guangxi **Class:** OTHER **Name:** Shenzhen Second People's Hospital #### Lead Sponsor **Class:** OTHER **Name:** Eye & ENT Hospital of Fudan University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Adjuvant Therapy Versus Endoscopic Surgery Alone in Early-stage Recurrent Nasopharyngeal Carcinoma: A Multicenter Randomized Controlled Trial **Detailed Description:** This study is an open-label, multicentered, evaluator-blinded , randomized clinical trial. Patients with early-stage recurrent nasopharyngeal carcinoma were randomized into the control group and the experimental group. Patients in the control group would go through observation and follow-up after recurrent endoscopic surgery, while patients in the experimental group would be treated with adjuvant therapy such as chemotherapy and immunotherapy. A total of 176 subjects are required, with 88 patients in the control group and 88 patients in the experimental group. ### Conditions Module **Conditions:** - Recurrent Nasopharyngeal Carcinoma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 176 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in the control group would go through observation and follow-up after recurrent endoscopic surgery. **Label:** The control group **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Patients in the experimental group would be implemented with adjuvant therapy including chemotherapy and immunotherapy after endoscopic surgery. **Intervention Names:** - Drug: Immunotherapy,Toripalimab Injection - Drug: Chemotherapy,Gemcitabine based regimen **Label:** The experimental group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - The experimental group **Description:** Patients in the experimental group would be implemented with adjuvant Immunotherapy and chemotherapy after endoscopic surgery. Four to six cycles chemotherapy and 10 cycles immunotherapy,or until unacceptable side effects. **Name:** Immunotherapy,Toripalimab Injection **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - The experimental group **Description:** Patients in the experimental group would be implemented with adjuvant Immunotherapy and chemotherapy after endoscopic surgery. Four to six cycles chemotherapy and 10 cycles immunotherapy,or until unacceptable side effects. **Name:** Chemotherapy,Gemcitabine based regimen **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Disease free survival **Measure:** DFS **Time Frame:** From date of randomization until the date of first documented recurrence, metastasis or date of death from any cause, whichever came first, assessed up to 24 months #### Secondary Outcomes **Description:** Overall Survival **Measure:** OS **Time Frame:** From randomization to death of any cause,assessed up to 60 months **Description:** Local recurrence free survival **Measure:** LRFS **Time Frame:** From randomization to local recurrence or death,assessed up to 24 months **Description:** Distant metastasis free survival **Measure:** DMFS **Time Frame:** From randomization to distant metastasis or death, assessed up to 24 months **Description:** one- and two-year disease free survival **Measure:** 1-and 2-year DFS rate **Time Frame:** end of 1st year, end of 2nd year **Description:** one- and two-year overall survival rate **Measure:** 1-and 2-year OS rate **Time Frame:** end of 1st year, end of 2nd year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Pathologically diagnosed with recurrent nasopharyngeal carcinoma; 2. Stage rT1 or rT2(superficial parapharyngeal space, distance to internal carotid artery ≤5mm)or rT3 (confined to the bottom wall of the sphenoid sinus),according to AJCC 8th edition; 3. Cervical lymph node metastasis can be controlled locally 4. Age 18 to 70 years; 5. Without distant metastasis; 6. Informed consent forms signed; 7. ≥6months from the accomplishment of radiation to recurrence 8. previously radiotherapy for only 1 course; 9. ECOG score 0-2 and can tolerate chemotherapy and immunotherapy 10. Sufficient organ function; 11. Undergone endoscopic surgery with negative pathological margin; Exclusion Criteria: 1. Participation in other interventional clinical trials; 2. Uncontrolled illnesses which will interfere with the ability to undergo therapy; 3. Suffering from another or multiple malignancy within 5 years (excluding fully treated basal cell or skin squamous cell carcinoma, cervical carcinoma in situ); 4. Any contradiction to immune and chemotherapy; 5. With serious autoimmune disease; 6. Currently usage of immunosuppressive agents or systemic glucocorticoid therapy (dosage\>10mg/day prednisone or other glucocorticoids), and continuing to use them within 2 weeks before the first administration of trial drugs; 7. Severe allergic reactions to other monoclonal antibodies; 8. Previously treatment with PD-1 monoclonal antibody, PD-L1 monoclonal antibody, CTLA-4 monoclonal antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathway); 9. History of radioactive particle planting; 10. Vaccination with live vaccine within 4 weeks prior to initial administration or possibly during the study period; 11. Female patients who are at pregnancy or lactation; 12. Other situations that the researchers believe are not suitable for enrollment **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** jxfxsxl@163.com **Name:** Xiaole Song, MD **Phone:** +8621 64377134 **Role:** CONTACT **Contact 2:** **Name:** Yuting Lai **Role:** CONTACT #### Locations **Location 1:** **City:** Shanghai **Country:** China **Facility:** Eye& ENT Hospital, Fudan University **State:** Shanghai **Zip:** 200031 **Location 2:** **City:** Fuzhou **Contacts:** ***Contact 1:*** - **Name:** Desheng Wang - **Role:** CONTACT ***Contact 2:*** - **Name:** Desheng Wang - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Haichun Lai - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** Fujian Medical University Union Hospital **Location 3:** **City:** Nanning **Contacts:** ***Contact 1:*** - **Name:** Shenhong Qu - **Role:** CONTACT ***Contact 2:*** - **Name:** Shenhong Qu - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Jingjin Weng - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** The People's Hospital of Guangxi Zhuang Autonomous Region **Location 4:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Name:** Haihong Tang - **Role:** CONTACT ***Contact 2:*** - **Name:** Haihong Tang - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Hongliang Zheng - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Haopu Li - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Fengya Pan - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** Changhai Hospital **Location 5:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Name:** Weitian Zhang - **Role:** CONTACT ***Contact 2:*** - **Name:** Weitian Zhang - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Ru Tang - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** Shanghai Sixth People's Hospital **Location 6:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Name:** Xinsheng Huang - **Role:** CONTACT ***Contact 2:*** - **Name:** Xinsheng Huang - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Xianhui Ning - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Lei Zhou - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Shanghai Zhongshan Hospital **Location 7:** **City:** Shenzhen **Contacts:** ***Contact 1:*** - **Name:** Yongtian Lu - **Role:** CONTACT ***Contact 2:*** - **Name:** Yongtian Lu - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Jing Tao - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Shenzhen Second People's Hospital #### Overall Officials **Official 1:** **Affiliation:** Eye& ENT Hospital, Fudan University **Name:** Hongmeng Yu **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Info Types:** - STUDY_PROTOCOL - ICF - CSR **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000009303 - Term: Nasopharyngeal Neoplasms - ID: D000010610 - Term: Pharyngeal Neoplasms - ID: D000010039 - Term: Otorhinolaryngologic Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009302 - Term: Nasopharyngeal Diseases - ID: D000010608 - Term: Pharyngeal Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M1730 - Name: Nasopharyngeal Carcinoma - Relevance: HIGH - As Found: Nasopharyngeal Carcinoma - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M12254 - Name: Nasopharyngeal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M13517 - Name: Pharyngeal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12962 - Name: Otorhinolaryngologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12253 - Name: Nasopharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M13515 - Name: Pharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - Relevance: LOW - As Found: Unknown - ID: T4047 - Name: Nasopharyngeal Carcinoma - Relevance: HIGH - As Found: Nasopharyngeal Carcinoma ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000077274 - Term: Nasopharyngeal Carcinoma - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M2985 - Name: Gemcitabine - Relevance: HIGH - As Found: Activity - ID: M2853 - Name: Immunomodulating Agents - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000093542 - Term: Gemcitabine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00784979 **Brief Title:** Panel Reactive Antibody (PRA) Reduction in Sensitized Patients Awaiting Renal Transplantation **Official Title:** Reduction of PRA (Panel Reactive Antibody) in Sensitized Patients Awaiting Live-Donor Renal Transplantation #### Organization Study ID Info **ID:** IIS_100109 #### Organization **Class:** OTHER **Full Name:** Tampa General Hospital ### Status Module #### Completion Date **Date:** 2012-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-06-29 **Type:** ESTIMATED **Last Update Submit Date:** 2015-06-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-06-29 **Type:** ESTIMATED **Results First Submit Date:** 2014-04-28 **Results First Submit QC Date:** 2015-06-22 #### Start Date **Date:** 2002-01 **Status Verified Date:** 2015-06 #### Study First Post Date **Date:** 2008-11-05 **Type:** ESTIMATED **Study First Submit Date:** 2008-11-04 **Study First Submit QC Date:** 2008-11-04 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** CSL Behring #### Lead Sponsor **Class:** OTHER **Name:** Tampa General Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to offer Panel Reactive Antibodies \[PRA\] reduction treatment to high responder renal transplant patients who otherwise may never be compatible with a potential organ donor. PRA reduction is offered in the following phases: 1. Immunological Testing 2. Transplant Nephrectomy 3. Pharmacologic Therapy 4. Plasmapheresis 5. Transplant **Detailed Description:** Patients with high level of preformed antibodies (panel reactive antibodies \[PRA\]) to donor antigens make identification of a suitable donor difficult. For most transplant centers, 20-35% of patients waiting for a kidney transplant comprise this challenging group. These patients have a wait time of over five years and have many incompatible cross-matches with potential organ donors. ### Conditions Module **Conditions:** - End Stage Renal Disease **Keywords:** - Renal - Transplant - PRA ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 26 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** MMF or rapamycin was given with CMVIG for 4 weeks followed by plasmapheresis **Intervention Names:** - Drug: CMVIG **Label:** CMVIG followed by PP **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - CMVIG followed by PP **Description:** 400mg/kg IV (60mg/kg/IV/hr initially, titrated up) once a week up to four weeks **Name:** CMVIG **Other Names:** - Cytomegalovirus Immune Globulin - Intravenous - Cytogam **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The percent of sensitized patients treated with PRA Reduction Pharmacological Therapy, including Cytogam, who become cross-match compatible with potential living donor. Treatment success defined as achieving a decrease in donor specific antibody and eliminating cross-match incompatibility sufficient to allow transplantation. **Measure:** The Percent of Sensitized Patients Treated With PRA Reduction Pharmacological Therapy, Including Cytogam, Who Become Cross-match Compatible With Potential Living Donor **Time Frame:** four weeks #### Secondary Outcomes **Measure:** Monitor Graft Survival **Time Frame:** 5 years **Measure:** Monitor Patient Survival **Time Frame:** 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Renal transplant recipients with a potential living donor who is incompatible (T-\&/or B-cell locus) due to recipient high PRA or MHC antibodies * PRA greater than or equal to 20% within last twelve months * Recipient and donor accepted as potential candidates by the LifeLink Healthcare Renal Transplant Committee Exclusion Criteria: * Patients with known allergy to CytoGam(R), Cellcept, Rapamycin * Patients who will receive IVIG or CytoGam(R) for any cause prior to protocol process * ABO incompatibility * Patients not capable of following through the treatment for various reasons as determined by treating physicians * Any potential recipient who is pregnant or becomes pregnant * Exclusion for Plasmapheresis: known allergy to ethylene oxide or natural rubber latex. * Exclusion for Plasmapheresis: Intake of ACE-inhibitor or Angtiotensiin-receptor blockers in the last 24 hours prior to plasma exchange **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tampa **Country:** United States **Facility:** LifeLink HealthCare Institute **State:** Florida **Zip:** 33606 #### Overall Officials **Official 1:** **Affiliation:** Lifelink Healthcare Institute **Name:** John Leone, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** Tampa General Medical Group **URL:** http://www.tgmg.org ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic - ID: D000051437 - Term: Renal Insufficiency - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M10699 - Name: Kidney Failure, Chronic - Relevance: HIGH - As Found: End Stage Renal Disease - ID: M26718 - Name: Renal Insufficiency - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M26717 - Name: Renal Insufficiency, Chronic - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007676 - Term: Kidney Failure, Chronic ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M21960 - Name: Sirolimus - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: HIGH - As Found: Cap - ID: M19117 - Name: Immunoglobulins, Intravenous - Relevance: LOW - As Found: Unknown - ID: M8836 - Name: gamma-Globulins - Relevance: LOW - As Found: Unknown - ID: M20191 - Name: Rho(D) Immune Globulin - Relevance: LOW - As Found: Unknown - ID: M353695 - Name: Temsirolimus - Relevance: LOW - As Found: Unknown - ID: M2827 - Name: MTOR Inhibitors - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007136 - Term: Immunoglobulins ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Highly Sensitized Patients **Description:** Highly-sensitized patients were defined as those having PRA greater than or equal to 20 percent within the last 12 months, identification of donor-specific antibody or, any combination of Class I and/or Class 2 HLA incompatibility. **ID:** EG000 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Highly Sensitized Patients **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 26 **Units:** Participants ### Group **ID:** BG000 **Title:** Highly Sensitized Patients **Description:** Highly-sensitized patients were defined as those having PRA \>/= 20% within the last 12 months; identification of donor-specific antibody or, any combination of Class I and/or Class 2 HLA incompatibility. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10.6 **Value:** 42 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 13 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 76 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Description:** \>/= 18 years old **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** NUMBER **Title:** Percent of subjects with PRA >/= 20% in last 12 months **Unit of Measure:** percent of subjects with elevated PRA ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** jpleone@tgh.org **Organization:** Tampa General Hospital **Phone:** 813-844-5666 **Title:** Dr. John Leone ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 40 **Title:** #### Outcome Measure 2 #### Outcome Measure 3 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The percent of sensitized patients treated with PRA Reduction Pharmacological Therapy, including Cytogam, who become cross-match compatible with potential living donor. Treatment success defined as achieving a decrease in donor specific antibody and eliminating cross-match incompatibility sufficient to allow transplantation. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** four weeks **Title:** The Percent of Sensitized Patients Treated With PRA Reduction Pharmacological Therapy, Including Cytogam, Who Become Cross-match Compatible With Potential Living Donor **Type:** PRIMARY **Unit of Measure:** percent of subjects becoming compatible ##### Group **Description:** Highly-sensitized patients were defined as those having PRA greater than or equal to 20 percent within the last 12 months, identification of donor-specific antibody or, any combination of Class I and/or Class 2 HLA incompatibility. **ID:** OG000 **Title:** Highly Sensitized Patients #### Outcome Measure 2 **Reporting Status:** NOT_POSTED **Time Frame:** 5 years **Title:** Monitor Graft Survival **Type:** SECONDARY #### Outcome Measure 3 **Reporting Status:** NOT_POSTED **Time Frame:** 5 years **Title:** Monitor Patient Survival **Type:** SECONDARY ### Participant Flow Module #### Group **Description:** MMF or rapamycin was given with CMVIG for 4 weeks followed by plasmapheresis **ID:** FG000 **Title:** CMVIG Followed by PP #### Period **Title:** Overall Study ##### Withdraw **Type:** incomplete data ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 26 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03626779 **Brief Title:** Bone Density in Immediate Implant Placment and Loading(BDIIPL) **Official Title:** Prf Controlled,Randamized Cinical Trial of EFFECTS OF THE PLATELET-RICH FIBRIN (PRF) ON BONE DENSITY IN IMMEDIATE IMPLANT PLACEMENT AND LOADING IN ESTHETIC ZONE #### Organization Study ID Info **ID:** Cairo U #### Organization **Class:** OTHER **Full Name:** Cairo University ### Status Module #### Completion Date **Date:** 2019-08-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2018-08-22 **Type:** ACTUAL **Last Update Submit Date:** 2018-08-21 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-08-30 **Type:** ESTIMATED #### Start Date **Date:** 2018-09-01 **Type:** ESTIMATED **Status Verified Date:** 2018-08 #### Study First Post Date **Date:** 2018-08-13 **Type:** ACTUAL **Study First Submit Date:** 2018-07-30 **Study First Submit QC Date:** 2018-08-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ahmed adel shaaban #### Responsible Party **Investigator Affiliation:** Cairo University **Investigator Full Name:** Ahmed adel shaaban **Investigator Title:** CairoU **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Atrumatic extraction ,immediate implant placment , prf as plug,immediate loading , mesure bone density 0-3-6-9 month **Detailed Description:** Atrumatic extraction unrestorable tooth in esthetic zone and immediate implant placment and withdrow 10cc blood sample to gain prf plug as membrane and immediate provisional for one week and final restoration after 1 week , and mesure bone density from 0-3-6-9 month ### Conditions Module **Conditions:** - Bone Density Increased ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 10 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Immediat placment and loading with prf **Intervention Names:** - Other: Prf **Label:** immediate placment and loading with prf **Type:** OTHER #### Arm Group 2 **Description:** Immediate implant placment and loading without prf **Label:** immediate implant placment and loading **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - immediate placment and loading with prf **Description:** Take 10cc blood from patient and gain prf blug **Name:** Prf **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Cbct **Measure:** Bone density enhancement with prf in immediate implant placment and loding **Time Frame:** 9 month ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * unrestorable anterior tooth. * Good oral hygine * Adequate bone hieght apical to the alveolus of failing tooth to ensure primary stability . Exclusion Criteria: * systematic disease which affect osteointgration. * Bad oral hygiene * Broxism, clenching, deep bite, edge to edge and abnormal habits. * Non-treated peeiodontal diseases. * Pregnancy and smokers. Severe infection. Loss of labial crest after extraction of failing tooth. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010009 - Term: Osteochondrodysplasias - ID: D000001848 - Term: Bone Diseases, Developmental - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12949 - Name: Osteosclerosis - Relevance: HIGH - As Found: Bone Density Increased - ID: M12932 - Name: Osteochondrodysplasias - Relevance: LOW - As Found: Unknown - ID: M12043 - Name: Mucopolysaccharidosis IV - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5127 - Name: Bone Diseases, Developmental - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: T3909 - Name: Mucopolysaccharidosis Type IV - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010026 - Term: Osteosclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01048879 **Brief Title:** Pharmacokinetics of Tamiflu® (Oseltamivir) in Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)and or Continuous Venovenous Hemodialysis (CVVHD) **Official Title:** Pharmacokinetics of Tamiflu® (Oseltamivir) in Patients Receiving CVVHD and/or ECMO #### Organization Study ID Info **ID:** HUM00033929 #### Organization **Class:** OTHER **Full Name:** University of Michigan ### Status Module #### Completion Date **Date:** 2010-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-08-21 **Type:** ESTIMATED **Last Update Submit Date:** 2012-07-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-01 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-08-21 **Type:** ESTIMATED **Results First Submit Date:** 2012-06-13 **Results First Submit QC Date:** 2012-07-17 #### Start Date **Date:** 2009-10 **Status Verified Date:** 2012-07 #### Study First Post Date **Date:** 2010-01-14 **Type:** ESTIMATED **Study First Submit Date:** 2010-01-13 **Study First Submit QC Date:** 2010-01-13 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Roche Pharma AG #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** Bruce A. Mueller **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Critically ill patients with flu may receive a drug called oseltamivir. They may also receive medical therapies to support their lung function (extracorporeal membrane oxygenation; ECMO) and kidney function (continuous venovenous hemodialysis; CVVHD). CVVHD and ECMO may remove some oseltamivir from the bloodstream. The purpose of this study is to determine how much oseltamivir gets removed by CVVHD or ECMO in critically ill patients. ### Conditions Module **Conditions:** - Critically Ill Renal Failure Requiring CVVHD and Oseltamivir - Critically Ill Requiring ECMO and Oseltamivir **Keywords:** - oseltamivir - influenza - continuous renal replacement therapy - extracorporeal membrane oxygenation - pharmacokinetics ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 15 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy (patients were already receiving oseltamivir and ECMO due to an illness)- Procedure/Surgery: pharmacokinetic blood sampling **Intervention Names:** - Procedure: pharmacokinetic blood sampling **Label:** ECMO alone **Type:** OTHER #### Arm Group 2 **Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir (Patients were already receiving oseltamivir and CVVHD as a result of an illness). Procedure/Surgery: pharmacokinetic blood and dialysate sampling **Intervention Names:** - Procedure: pharmacokinetic blood and dialysate sampling **Label:** CVVHD Alone **Type:** OTHER #### Arm Group 3 **Description:** Patient receiving oseltamivir and ECMO and CVVHD (patients were already receiving oseltamivir, ECMO, and CVVHD as part of an illness). Procedure/Surgery: pharmacokinetic blood and dialysate sampling **Intervention Names:** - Procedure: pharmacokinetic blood and dialysate sampling **Label:** CVVHD + ECMO **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - ECMO alone **Description:** blood samples collected to assess oseltamivir concentrations **Name:** pharmacokinetic blood sampling **Other Names:** - Tamiflu **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - CVVHD + ECMO - CVVHD Alone **Description:** blood and dialysate samples collected and assayed for oseltamivir concentrations **Name:** pharmacokinetic blood and dialysate sampling **Other Names:** - Tamiflu **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Oseltamivir Carboxylate Transmembrane Clearance by Continuous Venovenous Hemodialysis (Reported in mL/min). **Measure:** Continuous Venovenous Hemodialysis (CVVHD)Oseltamivir Carboxylate Transmembrane Clearance **Time Frame:** 12 hours **Description:** Mean percent change in oseltamivir carboxylate concentration pre- and post-oxygenator. **Measure:** Oseltamivir Carboxylate Removal by ECMO **Time Frame:** 12 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * receiving Continuous Venovenous Hemodialysis (CVVHD) or Extracorporeal Membrane Oxygenation (ECMO) * require oseltamivir treatment * informed consent granted Exclusion Criteria: * pregnant * unable to complete 12 hours of CVVHD or ECMO * \<6 kg body weight * allergy to oseltamivir **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ann Arbor **Country:** United States **Facility:** University of Michigan Hospital **State:** Michigan **Zip:** 48109 #### Overall Officials **Official 1:** **Affiliation:** University of Michigan **Name:** Bruce A Mueller, Pharm.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Eyler RF, Heung M, Pleva M, Sowinski KM, Park PK, Napolitano LM, Mueller BA. Pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill patients receiving continuous venovenous hemodialysis and/or extracorporeal membrane oxygenation. Pharmacotherapy. 2012 Dec;32(12):1061-9. doi: 10.1002/phar.1151. **PMID:** 23208833 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M19010 - Name: Critical Illness - Relevance: HIGH - As Found: Critically Ill - ID: M10295 - Name: Influenza, Human - Relevance: LOW - As Found: Unknown - ID: M26718 - Name: Renal Insufficiency - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000016638 - Term: Critical Illness ### Intervention Browse Module - Ancestors - ID: D000019999 - Term: Pharmaceutical Solutions - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M18008 - Name: Dialysis Solutions - Relevance: HIGH - As Found: Immunosuppression - ID: M27146 - Name: Oseltamivir - Relevance: HIGH - As Found: Repetitions of - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000053139 - Term: Oseltamivir - ID: D000015314 - Term: Dialysis Solutions ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** ECMO Alone **Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy **ID:** EG000 **Other Num at Risk:** 1 **Serious Number At Risk:** 1 **Title:** ECMO Alone **Group ID:** EG001 **Title:** CVVHD Alone **Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir **ID:** EG001 **Other Num at Risk:** 9 **Serious Number At Risk:** 9 **Title:** CVVHD Alone **Group ID:** EG002 **Title:** CVVHD + ECMO **Description:** Patient receiving oseltamivir and ECMO and CVVHD **ID:** EG002 **Other Num at Risk:** 5 **Serious Number At Risk:** 5 **Title:** CVVHD + ECMO **Frequency Threshold:** 5 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 1 **Group ID:** BG001 **Value:** 9 **Group ID:** BG002 **Value:** 5 **Group ID:** BG003 **Value:** 15 **Units:** Participants ### Group **ID:** BG000 **Title:** ECMO Alone **Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy ### Group **ID:** BG001 **Title:** CVVHD Alone **Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir ### Group **ID:** BG002 **Title:** CVVHD + ECMO **Description:** Patient receiving oseltamivir and ECMO and CVVHD ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 2 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 13 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0 **Value:** 48 #### Measurement **Group ID:** BG001 **Spread:** 10.2 **Value:** 33.0 #### Measurement **Group ID:** BG002 **Spread:** 16.1 **Value:** 32.2 #### Measurement **Group ID:** BG003 **Spread:** 12.4 **Value:** 33.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 4 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 11 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 9 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 15 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** muellerb@umich.edu **Organization:** University of Michigan **Phone:** 7346154578 **Title:** Bruce A. Mueller ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.0 - **Upper Limit:** - **Value:** 52.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.7 - **Upper Limit:** - **Value:** 43.3 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.101 - **Upper Limit:** - **Value:** -0.008 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.082 - **Upper Limit:** - **Value:** -0.033 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Oseltamivir Carboxylate Transmembrane Clearance by Continuous Venovenous Hemodialysis (Reported in mL/min). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One patient in the CVVHD Alone group was excluded from the analysis because not enough data points were available for pharmacokinetic modeling. **Reporting Status:** POSTED **Time Frame:** 12 hours **Title:** Continuous Venovenous Hemodialysis (CVVHD)Oseltamivir Carboxylate Transmembrane Clearance **Type:** PRIMARY **Unit of Measure:** mL/min ##### Group **Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir **ID:** OG000 **Title:** CVVHD Alone ##### Group **Description:** Patients receiving oseltamivir and ECMO and CVVHD **ID:** OG001 **Title:** CVVHD + ECMO ##### Group **Description:** Patients receiving ECMO only **ID:** OG002 **Title:** ECMO Alone #### Outcome Measure 2 **Description:** Mean percent change in oseltamivir carboxylate concentration pre- and post-oxygenator. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All of the patients that received ECMO were included. Patients receiving CVVHD Alone did not receive ECMO and were not included. **Reporting Status:** POSTED **Time Frame:** 12 hours **Title:** Oseltamivir Carboxylate Removal by ECMO **Type:** PRIMARY **Unit of Measure:** percent change in concentration ##### Group **Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir **ID:** OG000 **Title:** CVVHD Alone ##### Group **Description:** Patients receiving oseltamivir and ECMO and CVVHD **ID:** OG001 **Title:** CVVHD + ECMO ##### Group **Description:** Patients receiving ECMO only **ID:** OG002 **Title:** ECMO Alone ### Participant Flow Module #### Group **Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy **ID:** FG000 **Title:** ECMO Alone #### Group **Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir **ID:** FG001 **Title:** CVVHD Alone #### Group **Description:** Patient receiving oseltamivir and ECMO and CVVHD **ID:** FG002 **Title:** CVVHD + ECMO #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 5 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 5 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03585179 **Acronym:** TRANEXAMICO **Brief Title:** Oral and Topical Tranexamic Acid for the Treatment of Melasma **Official Title:** Oral and 5% Topical Tranexamic Acid in Monotherapy Compared With 4% Topical Hydroquinone for the Treatment of Melasma: Three-arm Randomized, Double-blinded Clinical Trial #### Organization Study ID Info **ID:** 151/2018 #### Organization **Class:** OTHER **Full Name:** Centro Dermatológico Dr. Ladislao de la Pascua ### Status Module #### Completion Date **Date:** 2020-06-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2018-07-16 **Type:** ACTUAL **Last Update Submit Date:** 2018-07-12 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2018-08-01 **Type:** ESTIMATED **Status Verified Date:** 2018-07 #### Study First Post Date **Date:** 2018-07-12 **Type:** ACTUAL **Study First Submit Date:** 2018-06-29 **Study First Submit QC Date:** 2018-07-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centro Dermatológico Dr. Ladislao de la Pascua #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** Tranexamic acid has been used for treating melasma due to its effect on decreasing the activity of tyrosinase and melanogenesis. This 3-arm clinical trial will asess the efficacy and safety of oral and topical tranexamic acid as monotherapy compared with topical hydroquinone for 12 weeks in adults with melasma. The primary outcome will be the percentage of reduction at 12-week period of mMASI and melanin index. The incidence of adverse effects will be reported at weeks 4, 8 and 12. **Detailed Description:** Tranexamic acid has been used for treating melasma due to its effect on decreasing the activity of tyrosinase and melanogenesis. This 3-arm clinical trial will asess the efficacy and safety of oral and topical tranexamic acid as monotherapy compared with topical hydroquinone for 12 weeks in adults with melasma. One hundred and twenty patients will be recruited in 3 groups of intervention: group I with tranexamic acid at a dose of 250 mg bid orally, group II with 5% topical tranexamic acid bid, group III with 4% topical hydroquinone once daily. The primary outcome will be the percentage of reduction at 12-week period of mMASI and melanin index. The incidence of adverse effects will be reported at weeks 4, 8 and 12. ### Conditions Module **Conditions:** - Melasma - Chloasma - Melanosis **Keywords:** - Melasma - Chloasma - Melanosis - Tranexamic acid - Hydroquinone - Therapeutics ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Three-arm clinical trial ##### Masking Info **Masking:** TRIPLE **Masking Description:** Participants will receive both topical and oral interventions. Group 1: pills of tranexamic acid 250 mg bid plus placebo gel bid, Group 2: pills of placebo bid plus 5% tranexamic acid gel bid and Group 3: pills of placebo bid plus 4% hydroquinone cream at night and a placebo cream at morning. Containers will be of identical appearance. **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 250 mg of tranexamic acid bid orally **Intervention Names:** - Drug: Oral Tranexamic Acid **Label:** Oral tranexamic acid **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 5% topical tranexamic acid bid **Intervention Names:** - Drug: 5% topical tranexamic acid **Label:** Topical tranexamic acid **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 4% hydroquinone once daily at night **Intervention Names:** - Drug: 4% hydroquinone **Label:** Topical hydroquinone **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Oral tranexamic acid **Description:** Participants will take a pill of 250 mg bid for 12 weeks **Name:** Oral Tranexamic Acid **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Topical tranexamic acid **Description:** Participants will apply a layer of gel on the affected skin bid for 12 weeks **Name:** 5% topical tranexamic acid **Other Names:** - Topical tranexamic acid **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Topical hydroquinone **Description:** Participants will apply a layer of cream on the affected skin once at night **Name:** 4% hydroquinone **Other Names:** - Hydroquinone **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The difference between mMASI (Modified Melasma Area and Severity Index) at week 0 and mMASI (Modified Melasma Area and Severity Index) at week 12 **Measure:** Change of mMASI (Modified Melasma Area and Severity Index) **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** The reported change of the score of DLQI (Dermatology Life Quality Index) at week 0 versus week 12. Total score ranges from 0 to 30 and the difference between the score at week 0 and week 12 will be calculated. **Measure:** Change in Quality of life **Time Frame:** 12 weeks **Description:** The difference between melanin index at week 0 versus week 12. The melanin index will be measure with Mexameter® MX 18. Total index ranges from 0 to 999. **Measure:** Melanin index **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age older than 18 years * Moderate to severe melasma * History of multiple topical depigmenting treatments and use of photoprotection, with subjective improvement less than 50% or mMASI \<50% reported by the dermatologist after one year of treatment. Exclusion Criteria: * Pregnancy * Hormonal contraception * Lactation * Treatment with hydroquinone or tranexamic acid at the time of the study or in the last 3 months * Endocrinology diseases * Hormone replacement therapy * Family or personal history of one of the following: autoimmune disorders, coagulation disorders, chronic venous insufficiency, heart diseases, retinopathies, kidney disorders * Mental disability **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** mmoraless@sersalud.df.gob.mx **Name:** Martha A Morales-Sánchez, MD **Phone:** 55387033 **Phone Ext:** 312 **Role:** CONTACT #### Locations **Location 1:** **City:** Mexico City **Country:** Mexico **Facility:** Centro Dermatológico "Dr. Ladislao de la Pascua" **Zip:** 06780 #### Overall Officials **Official 1:** **Affiliation:** Centro Dermatológico Dr. Ladislao de la Pascua **Name:** Martha A Morales-Sánchez, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** Only if researchers ask for the complete data of the trial. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000017495 - Term: Hyperpigmentation - ID: D000010859 - Term: Pigmentation Disorders - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M11531 - Name: Melanosis - Relevance: HIGH - As Found: Melasma - ID: M19760 - Name: Hyperpigmentation - Relevance: LOW - As Found: Unknown - ID: M13754 - Name: Pigmentation Disorders - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008548 - Term: Melanosis ### Intervention Browse Module - Ancestors - ID: D000000933 - Term: Antifibrinolytic Agents - ID: D000050299 - Term: Fibrin Modulating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000006490 - Term: Hemostatics - ID: D000003029 - Term: Coagulants - ID: D000000975 - Term: Antioxidants - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000011837 - Term: Radiation-Protective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Coag - Name: Coagulants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Derm - Name: Dermatologic Agents ### Intervention Browse Module - Browse Leaves - ID: M16902 - Name: Tranexamic Acid - Relevance: HIGH - As Found: Needs - ID: M6263 - Name: Coal Tar - Relevance: LOW - As Found: Unknown - ID: M261781 - Name: Hydroquinone - Relevance: HIGH - As Found: Blood Lipid - ID: M4252 - Name: Antifibrinolytic Agents - Relevance: LOW - As Found: Unknown - ID: M9576 - Name: Hemostatics - Relevance: LOW - As Found: Unknown - ID: M6259 - Name: Coagulants - Relevance: LOW - As Found: Unknown - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: M14684 - Name: Radiation-Protective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014148 - Term: Tranexamic Acid - ID: C000031927 - Term: Hydroquinone ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03145779 **Brief Title:** Evaluation of Phenotypic Variability in Fabry Disease **Official Title:** Evaluation of Phenotypic Variability in Fabry Disease #### Organization Study ID Info **ID:** IRB-P00022060 #### Organization **Class:** OTHER **Full Name:** Boston Children's Hospital ### Status Module #### Completion Date **Date:** 2030-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2020-12-03 **Type:** ACTUAL **Last Update Submit Date:** 2020-12-01 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2030-07 **Type:** ESTIMATED #### Start Date **Date:** 2020-07 **Type:** ESTIMATED **Status Verified Date:** 2020-12 #### Study First Post Date **Date:** 2017-05-09 **Type:** ACTUAL **Study First Submit Date:** 2017-05-03 **Study First Submit QC Date:** 2017-05-04 **Why Stopped:** Funding ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Boston Children's Hospital #### Responsible Party **Investigator Affiliation:** Boston Children's Hospital **Investigator Full Name:** Farrah Rajabi **Investigator Title:** Instructor, Division of Genetics and Genomics **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Cerebrovascular events, such as stroke, are a devastating complication of Fabry disease that results in part from storage of complex lipids in both large and small vessels. Understanding how the genotype influences the phenotype or clinical presentation can help us understand which patients are at risk for the complications of Fabry disease. This study aims to follow the natural history of this disease will help us understand and predict long-term outcomes for patients. **Detailed Description:** This longitudinal study will be conducted at Boston Children's Hospital (BCH). Subjects recruited for the study will have routine clinical care assessment with a complete physical and neurological exam and biochemical monitoring with venipuncture. In addition as part of the study, subjects will be given questionnaires to assess details of medical and psychosocial history, will complete self-reported measures of neuropsychological evaluation, pain scores, quality of life, executive functioning and cognitive functioning. All patients assessments will be repeated every 2 years. ### Conditions Module **Conditions:** - Fabry Disease ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time. **Measure:** Globotriaosylceramide level, plasma **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time. **Measure:** Globotriaosylceramide level, urine **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Wechsler Adult Intelligence Scale - Revised (WAIS-R) to assess for any changes in intelligence scale over time. **Measure:** Intelligence scale assessment **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Single score based on questionnaire about quality of life to assess for any changes in scores over time. **Measure:** Quality of life questionnaire **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Single score based on testing of digit span backwards test, letter fluency, and category fluency to assess any changes in executive function over time. **Measure:** Executive functioning test **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Single score based on questionnaire about pain to evaluate progression of pain scores over time. **Measure:** Pain questionnaire **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Physical exam to evaluate for the development of angiokeratoma lesions and neurological symptoms development over time. **Measure:** Physical exam **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. #### Secondary Outcomes **Description:** High-throughput RNA sequencing will be done on plasma and peripheral blood lymphocytes to evaluate for changes over time. **Measure:** Transcriptome analysis **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Comprehensive metabolite mapping of biochemical pathways to determine any metabolomic pathway changes in Fabry disease patients over time. **Measure:** Metabolomic analysis **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Optional stool sample will be obtained for microbiome analysis to detect the microbiome progression over time in Fabry disease patients. **Measure:** Microbiome analysis **Time Frame:** Data will be obtained and studied every 2 years for up to 10 years. **Description:** Investigators will analyze sequencing results to determine the ability of whole exome sequencing to detect pathogenic modifiers of the Fabry disease phenotype. **Measure:** Targeted exome sequencing for evaluation of potential modifiers of Fabry disease phenotype. **Time Frame:** Data will be obtained one time at initial study visit ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Individuals who carry a classic alpha-galactosidase gene (GLA) mutation * All ages * Medical records available including previous genetic testing. * Capable of providing informed consent with assent for patients less than 18 years * Not currently involved in any other clinical trials. Exclusion Criteria: * No medical records available * No record of genotype * Not capable of providing informed consent * Currently involved in any clinical trial **Minimum Age:** 1 Year **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Patients with a diagnosis of Fabry disease. ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Boston Children's Hospital **State:** Massachusetts **Zip:** 02115 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013106 - Term: Sphingolipidoses - ID: D000020140 - Term: Lysosomal Storage Diseases, Nervous System - ID: D000020739 - Term: Brain Diseases, Metabolic, Inborn - ID: D000001928 - Term: Brain Diseases, Metabolic - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000059345 - Term: Cerebral Small Vessel Diseases - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000040181 - Term: Genetic Diseases, X-Linked - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000008661 - Term: Metabolism, Inborn Errors - ID: D000008064 - Term: Lipidoses - ID: D000008052 - Term: Lipid Metabolism, Inborn Errors - ID: D000016464 - Term: Lysosomal Storage Diseases - ID: D000008659 - Term: Metabolic Diseases - ID: D000052439 - Term: Lipid Metabolism Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4124 - Name: Fabry Disease - Relevance: HIGH - As Found: Fabry Disease - ID: M15904 - Name: Sphingolipidoses - Relevance: LOW - As Found: Unknown - ID: M18871 - Name: Lysosomal Storage Diseases - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5205 - Name: Brain Diseases, Metabolic - Relevance: LOW - As Found: Unknown - ID: M22498 - Name: Brain Diseases, Metabolic, Inborn - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M29437 - Name: Cerebral Small Vessel Diseases - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M24877 - Name: Genetic Diseases, X-Linked - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M11641 - Name: Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M11064 - Name: Lipidoses - Relevance: LOW - As Found: Unknown - ID: M11054 - Name: Lipid Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: T2169 - Name: Fabry Disease - Relevance: HIGH - As Found: Fabry Disease - ID: T5335 - Name: Sphingolipidosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000795 - Term: Fabry Disease ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05355779 **Brief Title:** Needs Assessment to Guide the Development of a Paediatric Survivorship Programme in Hong Kong **Official Title:** Needs Assessment to Guide the Development of a Paediatric Survivorship Programme in Hong Kong to Promote Physical and Psychological Well-being of Children After Cancer Treatment #### Organization Study ID Info **ID:** HKCH-REC-2021-056 #### Organization **Class:** OTHER **Full Name:** The Hong Kong Polytechnic University ### Status Module #### Completion Date **Date:** 2023-12-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-09-30 **Type:** ACTUAL #### Start Date **Date:** 2022-08-01 **Type:** ACTUAL **Status Verified Date:** 2022-08 #### Study First Post Date **Date:** 2022-05-02 **Type:** ACTUAL **Study First Submit Date:** 2022-01-24 **Study First Submit QC Date:** 2022-04-27 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Health and Medical Research Fund #### Lead Sponsor **Class:** OTHER **Name:** The Hong Kong Polytechnic University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study aims to fill the gaps in knowledge regarding the effects of cancer and its treatment on Hong Kong Chinese paediatric cancer survivors, especially during the transition period, to further capture a deeper understanding of the challenges, views and needs of Hong Kong Chinese paediatric cancer survivors and the key stakeholders around them via face-to-face conversations. **Detailed Description:** Objectives: Although increasing attention has been devoted to the development of paediatric cancer survivorship programmes, most of these studies have originated in Western countries. Given the cultural differences between Asian and Western communities, the applicability of the findings to paediatric cancer survivors in Asian cultural contexts is limited. To date, research remains scant regarding the needs and challenges of Hong Kong Chinese paediatric cancer survivors and the key stakeholders involved during the transition period after cancer treatment. Although Hong Kong paediatric cancer survivors do attend regular medical follow-up visits, most attention has been focused on their physiological care, while their psychosocial needs remain unmet. Accordingly, the aim of this proposed study will be to fill the gaps in knowledge regarding the effects of cancer and its treatment, especially will focus on psychosocial effects in Hong Kong Chinese paediatric cancer survivors during the transition period. Design and subjects: A qualitative descriptive design will be used. A purposive sample of 15 paediatric cancer survivor participants and their parents or caregivers, five paediatric oncology nurses and three paediatric oncologists will be invited for a semi-structured interview conducted with the aid of an interview guide. Data analysis: A thematic analysis approach will be used for data analysis. Expected results: The findings of this study will provide an in-depth understanding of the needs, challenges and views of paediatric cancer survivors and other key stakeholders, which will greatly facilitate the future development of appropriate targeted paediatric cancer survivorship programmes. ### Conditions Module **Conditions:** - Pediatric Cancer - Survivorship **Keywords:** - Paediatric Cancer - Survivorship - Post-treatment - Transition period - Qualitative study - Rehabilitation - Needs - Preferences ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** OTHER #### Enrollment Info **Count:** 38 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Paediatric cancer survivors, their parent/caregiver and health care professionals will be invited to express their views and perspectives in an interview with the researcher **Intervention Names:** - Other: Not Application as this is a qualitative study **Label:** Interviewees ### Interventions #### Intervention 1 **Arm Group Labels:** - Interviewees **Description:** Not Application as this is a qualitative study **Name:** Not Application as this is a qualitative study **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Semi-structured and open-ended questions will be used to collect qualitative data from the participants **Measure:** An individual, a face-to-face interview will be conducted with the participants to identify the needs of paediatric cancer survivors during the transition period after cancer treatment **Time Frame:** through study completion, an average of 15 months **Description:** Semi-structured and open-ended questions will be used to collect qualitative data from the participants **Measure:** An individual, a face-to-face interview will be conducted with the participants to assess the key elements in the development of a paediatric survivorship programme **Time Frame:** through study completion, an average of 15 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * able to speak Cantonese and read Chinese * aged between 9 and 18 years of age * Should have completed cancer treatment between 2 months and 2 years earlier Exclusion Criteria: * Children who received a diagnosis and completed treatment before the age of 9 will be excluded as they might have vague memories of the course of cancer and may have limited verbal and cognitive ability to express themselves * Children of exclude parents will be exclueded **Maximum Age:** 18 Years **Minimum Age:** 9 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** Paediatric cancer survivors ### Contacts Locations Module #### Locations **Location 1:** **City:** Hong Kong **Country:** Hong Kong **Facility:** The Hong Kong Children's Hospital #### Overall Officials **Official 1:** **Affiliation:** Hong Kong Polytechnic University **Name:** Joyce Chung **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03420079 **Brief Title:** A Phase I Study of FCN-411 in Advanced Non-small Cell Lung Cancer Chinese Patients With EGFR Positive Mutation **Official Title:** A Phase I, Multi-center, Open-label, Single-arm, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activities of FCN-411 Monotherapy in Advanced Non-small Cell Lung Cancer #### Organization Study ID Info **ID:** FCN001 #### Organization **Class:** OTHER **Full Name:** Ahon Pharmaceutical Co., Ltd. ### Status Module #### Completion Date **Date:** 2021-12-20 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-07-16 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2018-08-01 **Type:** ACTUAL **Status Verified Date:** 2020-07 #### Study First Post Date **Date:** 2018-02-05 **Type:** ACTUAL **Study First Submit Date:** 2017-11-14 **Study First Submit QC Date:** 2018-02-01 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Cancer Institute and Hospital, Chinese Academy of Medical Sciences #### Lead Sponsor **Class:** OTHER **Name:** Ahon Pharmaceutical Co., Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This phase I trial with dose-escalation stage and dose-expansion stage is the first-in-human study of FCN-411, a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of FCN-411 monotherapy in EGFR-positive mutation non-small cell lung cancer chinese patients. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the anti-tumor activities of FCN-411. **Detailed Description:** This is a multicenter, open, single arm phase I clinical trial to explore the dose of FCN-411 in advanced lung cancer patients with disease progression after standard treatment or unsuitable for standard treatment and to expand the dose in advanced NSCLC patients who failed EGFR-TKI treatment. During the screening period, patients need to provide tumor tissue/ blood samples collected after their disease progression for tumor biomarker detection. In this study, the safety, tolerance and pharmacokinetic characteristics of FCN-411 were observed by dose escalation study and dose expansion study, and the antitumor activity of FCN-411 was preliminarily evaluated to determine maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D). The phase I dose escalation study includes two stages: single dose stage and continuous dose stage; phase I dose expansion study is continuous dose administration. The research cycle is made up of screening period (day-28-day-1), single administration period (7 days), continuous administration period (every 21 days, evaluated every 6 weeks, until disease progression, intolerable toxicity, death, decision of the investigator or voluntary withdrawal of the patient), end of treatment, EOT) visit, safety follow-up (30 days after the last administration), survival follow-up (survival follow-up every 3 months from the safety follow-up until the end of the study). The end of study is one year after the first administration of the last enrolled patient or the end of treatment (whichever is earlier). ### Conditions Module **Conditions:** - Lung Cancer **Keywords:** - advanced NSCLC - EGFR-TKI refractory ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SEQUENTIAL **Intervention Model Description:** In the dose escalation cohort of FCN-411, the dose will be escalated from 4 mg, 8 mg, 16 mg, 24 mg to 32 mg. The MTD will be expanded to ascertain the RP2D. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 90 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * FCN-411 will be orally administrated at five sequential dose levels, which are 4 mg, 8 mg, 16 mg, 24 mg, and 32 mg. * Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). * Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles. **Intervention Names:** - Drug: FCN-411 Dose-escalation **Label:** Dose escalation cohort of FCN-411 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** * FCN-411 will be orally administrated at MTD. * Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). * Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles. **Intervention Names:** - Drug: FCN-411 Dose-expansion **Label:** Dose expansion cohort of FCN-411 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dose escalation cohort of FCN-411 **Description:** * FCN-411 is a pan EGFR inhibitor, which has strong activity against wild type (WT), HER2, HER4 and EGFR sensitive mutations (including but not limited to T790M and L858R mutation). * FCN-411 shows significant antitumor activity in a dose-dependent manner in in vivo models of lung cancer, esophageal cancer and pharyngeal squamous cell carcinoma mediated by EGFR. **Name:** FCN-411 Dose-escalation **Other Names:** - EGFR-TKI **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Dose expansion cohort of FCN-411 **Description:** * FCN-411 is a pan EGFR inhibitor, which has strong activity against wild type (WT), HER2, HER4 and EGFR sensitive mutations (including but not limited to T790M and L858R mutation). * FCN-411 shows significant antitumor activity in a dose-dependent manner in in vivo models of lung cancer, esophageal cancer and pharyngeal squamous cell carcinoma mediated by EGFR. **Name:** FCN-411 Dose-expansion **Other Names:** - EGFR-TKI **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Cmax of FCN-411 following single dose. **Measure:** Cmax of FCN-411 following single dose. **Time Frame:** PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose. **Description:** AUC of FCN-411 After Single Dosing. **Measure:** AUC of FCN-411 following single dose. **Time Frame:** PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose. **Description:** Cmax of FCN-411 After multiple dosing. **Measure:** Cmax of FCN-411 following multiple dosing. **Time Frame:** The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days. **Description:** AUC of FCN-411 After Multiple Dosing. **Measure:** AUC of FCN-411 following multiple dosing. **Time Frame:** The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days. **Description:** Tmax of FCN-411 following single dose. **Measure:** Tmax of FCN-411 following single dose. **Time Frame:** PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose. **Description:** Tmax of FCN-411 following multiple dosing. **Measure:** Tmax of FCN-411 following multiple dosing. **Time Frame:** The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days. **Description:** t1/2 of FCN-411 following single dose. **Measure:** t1/2 of FCN-411 following single dose. **Time Frame:** PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose. **Description:** t1/2 of FCN-411 following multiple dosing **Measure:** t1/2 of FCN-411 following multiple dosing **Time Frame:** The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age 18 years and older. 2. Histological or cytological confirmed diagnosed advanced or metastatic NSCLC. 3. Documentation of disease progression while on previous continuous treatment with first-line EGFR TKI; patients must have confirmation of tumor EGFR activating mutations (exon 19 del, or exon 21 ins) and T790M status by biopsy sample or optical microscopy. 4. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG). 5. Have a life expectancy of at least 12 weeks. 6. Have measurable disease based on RECIST v1.1. Note: previously irradiated not chosen, unless disease progression after irradiation. 7. Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: 1. Neutrophils (absolute value) ≥ 1.5×10\^9/L; 2. Hemoglobin ≥ 90 g/L; 3. Platelet ≥ 90×10\^9/L; 4. Serum total bilirubin ≤ 1.5× ULN（for Patients with Gilbert Syndrome, total bilirubin ≤ 3×ULN and bilirubin ≤ 1.5×ULN should be permitted） 5. Aspartate aminotransferase、alanine aminotransferase ≤ 2.5×ULN; for patients with hepatic metastases, AST、ALT ≤ 5×ULN; 6. Creatinine \< 1.5×ULN creatinine clearance rate≥ 45 mL/min (Cockcroft Gault for calculating) 8. Female subjects have a negative urine or serum pregnancy. Exclusion Criteria: 1. Treatment with any of the following: 1. Treatment with an EGFR TKI within 14 days or about 5 half-lives, whichever is the longer, of the first dose of study drug; 2. Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment from a previous treatment regimen within 14 days of the first dose of study treatment; 3. Major surgery within 4 weeks of the first dose of study treatment; 4. Systemic irradiation including whole brain irradiation; 5. Previously treated by EGFR-TKI for T790M (for example Osimertinib). 2. P-glycoprotein inducers (for example Rifampicin) or inhibitors (for example ritonavir) are required during the study. 3. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy. 4. Meningeal metastases or CNS metastasis received intervention or malignancy related epilepsy; brain metastases without symptom are eligible. 5. Any serious or uncontrolled systemic disease, including but not limited to: 1. Uncontrolled hypertension; 2. Active hemorrhage; 3. Active infections including hepatitis B, or hepatitis C; 4. Human immunodeficiency virus positive; 5. Child Pugh C; 6. Bullous or exfoliative skin diseases; 7. Severe malnutrition; 8. History of keratitis or ulcerative keratitis or dry eye; 9. Uncontrolled large amount of third interstitial fluid retention; 10. Other serious diseases or mental disorders or laboratory abnormalities. 6. Cardiac function and disease are consistent with the following: 1. QTc\> 470 milliseconds from 3 electrocardiograms (ECGs); 2. Any clinically important abnormalities in rhythm; 3. Any factors that increase the risk of QTc prolongation; 4. Congestive heart failure ≥ grade 3 by New York Heart Association (NYHA); 7. Previous history with interstitial lung disease、drug-induced interstitial lung disease or radiation pneumonitis require hormone therapy, or other active interstitial lung diseases required treatments. 8. Lung function met one of the following criteria: 1. Oxygen saturation ≤ 88%; 2. The first second forced expiratory volume\< 50% of the predicted value; 3. Diffusion capacity for CO \< 50% of the predicted value. 9. Dysphagia, or active digestive system diseases or medical conditions potentially affect FCN-411 absorption. 10. Hypersensitivity to FCN-411 or similar compounds or excipients. 11. Pregnant or lactating women. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** syuankaipumc@126.com **Name:** yuankai Shi, MD **Phone:** 010-87788298 **Role:** CONTACT **Contact 2:** **Email:** huxingsheng66@163.com **Name:** xingsheng hu, MD **Phone:** 010-87788298 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** syuankaipumc@126.com - **Name:** yuankai Shi, MD - **Phone:** 01087788298 - **Role:** CONTACT ***Contact 2:*** - **Email:** huxingsheng66@163.com - **Name:** xingsheng hu, MD - **Phone:** 01087788298 - **Role:** CONTACT **Country:** China **Facility:** Cancer hospital chinese academy fo medical scienced **Status:** RECRUITING **Zip:** 100021 #### Overall Officials **Official 1:** **Affiliation:** Cancer Institute and Hospital, Chinese Academy of Medical Sciences **Name:** Yuankai Shi, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1. **PMID:** 23816960 **Citation:** Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1. Epub 2014 Jan 15. **PMID:** 24439929 **Citation:** Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. doi: 10.1016/S1470-2045(12)70086-4. Epub 2012 Mar 26. **PMID:** 22452895 **Citation:** Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Goker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. doi: 10.1016/S1470-2045(15)00006-6. Epub 2015 Jul 5. **PMID:** 26156651 **Citation:** Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Epub 2012 Mar 26. Erratum In: Lancet Oncol. 2012 May;13(5):e186. **PMID:** 22452896 **Citation:** Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 2013 Jul 1. **PMID:** 23816963 **Citation:** Wong AL, Sundar R, Wang TT, Ng TC, Zhang B, Tan SH, Soh TI, Pang AS, Tan CS, Ow SG, Wang L, Mogro J, Ho J, Jeyasekharan AD, Huang Y, Thng CH, Chan CW, Hartman M, Iau P, Buhari SA, Goh BC, Lee SC. Phase Ib/II randomized, open-label study of doxorubicin and cyclophosphamide with or without low-dose, short-course sunitinib in the pre-operative treatment of breast cancer. Oncotarget. 2016 Sep 27;7(39):64089-64099. doi: 10.18632/oncotarget.11596. **PMID:** 27577069 **Citation:** Lin L, Pan H, Li X, Zhao C, Sun J, Hu X, Zhang Y, Wang M, Ren X, Luo X, Shan G, Hui AM, Wu Z, Liu H, Tian L, Shi Y. A phase I study of FCN-411, a pan-HER inhibitor, in EGFR-mutated advanced NSCLC after progression on EGFR tyrosine kinase inhibitors. Lung Cancer. 2022 Apr;166:98-106. doi: 10.1016/j.lungcan.2022.01.025. Epub 2022 Feb 3. **PMID:** 35248866 #### See Also Links **Label:** ICH Topic E6 - Guideline for Good Clinical Practice: Consolidated guideline finalised (step 4) in May 1996. Adopted by CPMP, July 96, issued as CPMP/ICH/135/95/step 5, post step errata, July 2002. **URL:** https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r1-guideline-good-clinical-practice_en.pdf **Label:** ICH Topic E9 - Statistical Principles for Clinical Trials: Consensus guideline finalised (step 4) on 5th February1998. Adopted by CPMP, March 1998, issued as CPMP/ICH/363/96/step 5. **URL:** https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-9-statistical-principles-clinical-trials-step-5_en.pdf ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02870179 **Brief Title:** Oxitone Sp02 Hypoxia Test Versus Reference Pulse Oximetry **Official Title:** Oxitone Sp02 Hypoxia Test Versus Reference Pulse Oximetry #### Organization Study ID Info **ID:** PR 2016-191 #### Organization **Class:** INDUSTRY **Full Name:** Oxitone Medical Ltd. ### Status Module #### Completion Date **Date:** 2016-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-04-20 **Type:** ACTUAL **Last Update Submit Date:** 2017-04-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-09 **Type:** ACTUAL #### Start Date **Date:** 2016-08 **Type:** ACTUAL **Status Verified Date:** 2017-04 #### Study First Post Date **Date:** 2016-08-17 **Type:** ESTIMATED **Study First Submit Date:** 2016-08-10 **Study First Submit QC Date:** 2016-08-12 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Clinimark, LLC #### Lead Sponsor **Class:** INDUSTRY **Name:** Oxitone Medical Ltd. #### Responsible Party **Investigator Affiliation:** Oxitone Medical Ltd. **Investigator Full Name:** Leon Eisen, PhD **Investigator Title:** Leon Eisen, CEO **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to conduct a SpO2 hypoxia evaluation of the Oxitone Medical Oxitone 1000 pulse oximeter. The Oxitone 1000 pulse oximeter will be evaluated during non-motion conditions over the range of 70-100% SpO2 in comparison to a Reference Pulse Oximeter. The study is observational in nature which quantifies device performance and accuracy in compassion to a Reference Pulse Oximeter. **Detailed Description:** The purpose of this study is to conduct a SpO2 hypoxia evaluation of the Oxitone Medical Oxitone 1000 pulse oximeter. The Oxitone 1000 pulse oximeter will be evaluated during non-motion conditions over the range of 70-100% SpO2 in comparison to a Reference Pulse Oximeter. The end goal is to show the SpO2 accuracy performance of the Oxitone 1000 and if needed, use the data to make improvements prior to an arterial blood hypoxia study. A Clinimark 3900 Reference Pulse Oximeter or Nellcor N-600x will be used for the SpO2 calibration. There are no risks or adverse device effects to be assessed. There are no contraindications for use in the proposed study / study population The Control Pulse Oximeter, GE Healthcare (Datex-Ohmeda) 3900, an FDA cleared device, is used to monitor the oxygen saturation levels real time throughout the study for subject safety and to target stable plateaus. This device is used to assess the stability of the data. ### Conditions Module **Conditions:** - Hypoxia **Keywords:** - Pulse Oximetry - Temperature - Respiratory Rate - Respiratory Gases - This study determines the measurement accuracy of the physiological parameters ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 11 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Smoker or non-smoker **Intervention Names:** - Device: Pulse Oximeter **Label:** Healthy volunteer ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy volunteer **Description:** Measurement of physiological parameters **Name:** Pulse Oximeter **Other Names:** - Blood Pressure - Respiratory Rate - Respiratory Gassess - Temperature **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Data is collected in a digital form for 4-6 SpO2 stable plateaus in a specified range from 100% to 70%. **Measure:** Collect SpO2 data for accuracy statistical analysis by 12 subjects **Time Frame:** 2 months **Description:** Bland-Altman graphical plots. An Accuracy Root Mean Square (ARMS) calculation is used as a means to define the SpO2 accuracy. Data analysis will follow ISO80601-2-61, Annex EE and the FDA Guidance Document for Pulse Oximeters (Martch 4, 2013). **Measure:** Accuracy data analysis **Time Frame:** 2 months #### Secondary Outcomes **Description:** SpO2 versus (SpO2-Ref SpO2) will be generated with linear regression fit, mean, and upper 95% and lower 95% limits of agreement. **Measure:** Error plots **Time Frame:** 2 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy individuals between the age of 18-50 Exclusion Criteria: * Clotting disorders, diabetes, currently taking psychotropic medications **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** Residents of the Denver metropolitan area ### Contacts Locations Module #### Locations **Location 1:** **City:** Louisville **Country:** United States **Facility:** Clinimark Laboratories **State:** Colorado **Zip:** 80027 #### Overall Officials **Official 1:** **Affiliation:** Oxitone Medical Ltd. **Name:** Leon Eisen, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012818 - Term: Signs and Symptoms, Respiratory ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4185 - Name: Hypoxia - Relevance: HIGH - As Found: Hypoxia - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000860 - Term: Hypoxia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05763979 **Brief Title:** Assesment of the Change in Consumer Behaviours to Afford the Dietary Cost According to Food Security Status and Choice Motives **Official Title:** Assesment of the Change in Consumer Behaviours to Afford the Dietary Cost According to Food Security Status and Choice Motives #### Organization Study ID Info **ID:** TIF-Con #### Organization **Class:** OTHER **Full Name:** Hacettepe University ### Status Module #### Completion Date **Date:** 2023-06-15 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-10 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-01 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-06-15 **Type:** ESTIMATED #### Start Date **Date:** 2023-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2023-03-10 **Type:** ACTUAL **Study First Submit Date:** 2023-03-01 **Study First Submit QC Date:** 2023-03-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hacettepe University #### Responsible Party **Investigator Affiliation:** Hacettepe University **Investigator Full Name:** Mehmet HAYDAROGLU **Investigator Title:** Research Assistant **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of this study is to assement of the change in consumer behaviours during the food inflation period in order to afford the dietary cost according to food security status and food choice motives. The study was planned in four stages. 1) First stage is adapting the Single-item Food Choice Questionnaire to Turkish society and to make its validity and reliability in Turkish. 2) The Impact of Food Inflation on Consumer Behavioural Change (TIF-Con) scale will be developed. 3) Observational cross-sectional data collection including these surveys will be carried out. 4) The Cost of the Recommended Diet (CoRD) will be calculated by collecting data simultaneously with the fieldwork. Hypotheses will be tested in line with the findings obtained. **Detailed Description:** The reliability and validity of the Single-item Food Choice Questionnaire was planned in eight stages. 1) Translation into Target Language 2) Synthesis of translations 3) Back translation to Original Language 4) Expert assessment 5) Pilot study 6) Reporting 7) Testing 8) Retesting. The development of the Impact of Food Inflation on Consumer Behavioural Change (TIF-Con) scale was planned in eight stages too. 1) Generating an item pool 2) Determining the format for measurement 3) Initial item pool reviewed by experts 4) Pretesting 5) Optimizing scale length 6) Testing 7) Retesting 8) Reporting. A cross-sectional survey will be conducted by questioning food security and socioeconomic status, along with the developed TIF-Con and the adapted food choice questionnaire. This stage will be combined with the sixth stage of scale development in order to act economically. Simultaneously, the CoRD will be calculated with the collection of food prices with fieldwork and the recommendations of the offical Turkey's dietary guideline. The obtained results will be analyzing to assesment of the change in consumer behaviours during the food inflation period in order to afford the dietary cost according to food security status and food choice motives. ### Conditions Module **Conditions:** - Food Selection - Consumer Behavior - Healthy Nutrition **Keywords:** - Food security - Food choice motives - Food inflation - Healthy Diet's Cost ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 400 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** The identifying of consumers' food choice motives with using the Single-item Food Choice Questionnaire **Measure:** Food choice motives **Time Frame:** 03.15.2023 **Description:** The identifying of the change in consumer behaviours during the food inflation period **Measure:** The Impact of Food Inflation on Consumer Behavioural Change **Time Frame:** 04.15.2023 #### Secondary Outcomes **Description:** Consumer behavioural changes' differences in afford the dietary cost according to food security status and food choice motives **Measure:** Consumer Behavioural Changes' Differences **Time Frame:** 06.15.2023 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged between 18-65 * Who volunteered to participate in the study * Adult individuals who have access to the Internet and agreed to participate in the study * Native language being Turkish * Living in Turkey at least five years Exclusion Criteria: * Those with a disease that requires a specific diet * Inability to use a computer, tablet or mobile phone * Native language not being Turkish * Those who have not lived in Turkey for at least five years **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** People who live in Turkey and meeting the inclusion criteria and volunteered to participate in the study ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** mthaydaroglu@gmail.com **Name:** Mehmet Haydaroglu, Res Assist **Phone:** +90 5302309818 **Role:** CONTACT #### Locations **Location 1:** **City:** Ankara **Contacts:** ***Contact 1:*** - **Email:** pbilgic@hacettepe.edu.tr - **Name:** Pelin Bilgic, Assoc Prof - **Phone:** +90 3123051094 - **Phone Ext:** 125 - **Role:** CONTACT ***Contact 2:*** - **Name:** Pelin Bilgic, Assoc Prof - **Role:** SUB_INVESTIGATOR **Country:** Turkey **Facility:** Hacettepe University Nutrition and Dietetics Department **Status:** RECRUITING ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05409079 **Brief Title:** Schulze Muscular Dystrophy Ability Clinical Study **Official Title:** Schulze Muscular Dystrophy Ability Clinical Study #### Organization Study ID Info **ID:** Schulze #### Organization **Class:** INDUSTRY **Full Name:** AbiliTech Medical Inc. ### Status Module #### Completion Date **Date:** 2023-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-05 **Type:** ACTUAL **Last Update Submit Date:** 2022-12-01 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-05-26 **Type:** ACTUAL **Status Verified Date:** 2022-12 #### Study First Post Date **Date:** 2022-06-08 **Type:** ACTUAL **Study First Submit Date:** 2022-06-03 **Study First Submit QC Date:** 2022-06-03 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Richard M. Schulze Family Foundation #### Lead Sponsor **Class:** INDUSTRY **Name:** AbiliTech Medical Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** True ### Description Module **Brief Summary:** The primary objective of the Schulze study is to evaluate the function of the upper limbs of subjects diagnosed with neuromuscular disorders, with and without use of the Abilitech Assist device in the clinic and home environments. Functional outcomes will include documenting active range of motion and the ability to perform activities of daily living (ADLs) using the standardized Canadian Occupational Performance Measure (COPM) and the Role Evaluation of Activities of Life (REAL) assessments. Secondary objectives are to assess the safety record and report on adverse events (AEs) and parameters related to device usage, including device usage time and the time required to don/doff the device. Secondary objectives also include characterization of user upper limb performance based on etiology. ### Conditions Module **Conditions:** - Muscular Dystrophies - Spinal Muscular Atrophy - Duchenne Muscular Dystrophy - Limb Girdle Muscular Dystrophy - FSHD - Cerebral Palsy - Becker Muscular Dystrophy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 35 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The Abilitech™ Assist device is a passively powered orthotic device designed to support and assist the arms of patients with neuromuscular weakness for activities of daily living. **Intervention Names:** - Device: Abilitech Assist **Label:** Abilitech Assist **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Abilitech Assist **Description:** The Abilitech™ Assist is an externally worn device supported by a body frame, which is designed to support and assist the arms in activities of daily living (ADL's). The Abilitech Assist is comprised of three parts: a modular body vest that adjusts to accommodate different body sizes, a single arm orthosis that attaches to the body vest, and an external power pack and controller for tensioning the arm's internal springs to adjust the arm's level of assist. The device augments a user's native arm function to provide lift assistance. Software customizes the spring tension for the level of assist required. The user can turn the system ON/OFF and toggle and adjust the level of assist (e.g., low, medium or high assist) using a pushbutton controller. **Name:** Abilitech Assist **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The Canadian Occupational Performance Measure is an evidence-based outcome measure designed to capture a client's self-perception of performance in everyday living, over time. The COPM results in two main scores - PERFORMANCE and SATISFACTION - each out of 10. PERFORMANCE and SATISFACTION scores can be generated for up to 5 individual occupational performance problems. Average PERFORMANCE and SATISFACTION scores can be calculated by summing individual problem scores and dividing by the number of problems. Change in scores for both PERFORMANCE and SATISFACTION can be calculated after a reassessment interval and a comparison of individual's score differences from Time 1 (assessment) to Time 2 (re-assessment). Increases in scores indicate improvement in task performance and satisfaction. **Measure:** Canadian Occupational Performance Measure (COPM) **Time Frame:** Change from Baseline before device intervention (30 days), and after device intervention (60 days) **Description:** The REAL is an instrument to help professionals assess an individuals ability to care for themselves at home, at school and in the community. This assessment includes 136 total items with two domains(ADL: 78 items, IADL:58 items) that are rated using a 4-point scale (0-3) to describe whether an individual is unable, sleds, occasionally, or frequently able to complete a task. Scores are summed for each domain and compared over time with increases in scores indicating improvement in each domain. **Measure:** Roll Evaluation of Activities of Life (REAL) assessment **Time Frame:** Change from Baseline before device intervention (30 days), and after device intervention (60 days) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Subjects between 10 and 99 years of age, with onset of neuromuscular conditions that cause quadriparesis 2. MMT score of 1-3 in the elbow, wrist and hand; and a MMT score of 2-3 in the shoulder of at least one of the subject's arms 3. Ability of subject to raise their forearm off of their lap or laptray 4. Willingness to comply and participate with the study protocol and attend the study sessions 5. Ability to communicate verbally and respond to questions and commands 6. Ability to provide informed consent 7. Selected for participation based on investigator discretion Exclusion Criteria: 1. Use of invasive ventilator 2. Open wounds or chronic pressure sores on upper extremities, neck, back or torso 3. Significantly unstable upper extremity joints 4. Unhealed bone fractures in the upper extremities 5. Active rotator cuff tear, grade 2 or 3 6. Surgical fixations limiting full passive range of motion 7. Uncontrolled upper-limb spasticity that significantly limits normal range of motion 8. Uncontrollable pain in the neck, shoulders or upper limbs 9. Ability to fully raise both hands simultaneously above their head with ease as defined by the investigator 10. Lack passive shoulder abduction of 120 degrees 11. Lack 90 degrees of passive elbow extension 12. Unable to follow instructions 13. Exhibit significant behavioral problems 14. Inability to provide consent **Minimum Age:** 10 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** info@abilitechmedical.com **Name:** Chief Executive Officer **Phone:** 833.225.3123 **Role:** CONTACT #### Locations **Location 1:** **City:** Saint Paul **Contacts:** ***Contact 1:*** - **Email:** research@gillettechildrens.com - **Name:** Research - **Role:** CONTACT **Country:** United States **Facility:** Gillette Children's **State:** Minnesota **Status:** RECRUITING **Zip:** 55101 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001925 - Term: Brain Damage, Chronic - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000001284 - Term: Atrophy - ID: D000020763 - Term: Pathological Conditions, Anatomical - ID: D000020966 - Term: Muscular Disorders, Atrophic - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000040181 - Term: Genetic Diseases, X-Linked - ID: D000020879 - Term: Neuromuscular Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000016472 - Term: Motor Neuron Disease - ID: D000019636 - Term: Neurodegenerative Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5796 - Name: Cerebral Palsy - Relevance: HIGH - As Found: Cerebral Palsy - ID: M12093 - Name: Muscular Dystrophies - Relevance: HIGH - As Found: Muscular Dystrophy - ID: M12090 - Name: Muscular Atrophy - Relevance: HIGH - As Found: Muscular Atrophy - ID: M12091 - Name: Muscular Atrophy, Spinal - Relevance: HIGH - As Found: Spinal Muscular Atrophy - ID: M4589 - Name: Atrophy - Relevance: LOW - As Found: Unknown - ID: M22185 - Name: Muscular Dystrophy, Duchenne - Relevance: HIGH - As Found: Becker Muscular Dystrophy - ID: M13157 - Name: Paralysis - Relevance: LOW - As Found: Unknown - ID: M26038 - Name: Muscular Dystrophies, Limb-Girdle - Relevance: HIGH - As Found: Limb Girdle Muscular Dystrophy - ID: M5207 - Name: Brain Injuries - Relevance: LOW - As Found: Unknown - ID: M5202 - Name: Brain Damage, Chronic - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M22697 - Name: Muscular Disorders, Atrophic - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M24877 - Name: Genetic Diseases, X-Linked - Relevance: LOW - As Found: Unknown - ID: M22619 - Name: Neuromuscular Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M18879 - Name: Motor Neuron Disease - Relevance: LOW - As Found: Unknown - ID: M4024 - Name: Amyotrophic Lateral Sclerosis - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: T3963 - Name: Muscular Dystrophy - Relevance: HIGH - As Found: Muscular Dystrophy - ID: T5342 - Name: Spinal Muscular Atrophy - Relevance: HIGH - As Found: Spinal Muscular Atrophy - ID: T698 - Name: Becker Muscular Dystrophy - Relevance: HIGH - As Found: Becker Muscular Dystrophy - ID: T1945 - Name: Duchenne Muscular Dystrophy - Relevance: HIGH - As Found: Duchenne Muscular Dystrophy - ID: T3425 - Name: Limb-girdle Muscular Dystrophy - Relevance: HIGH - As Found: Limb Girdle Muscular Dystrophy - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T349 - Name: Amyotrophic Lateral Sclerosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009136 - Term: Muscular Dystrophies - ID: D000020388 - Term: Muscular Dystrophy, Duchenne - ID: D000049288 - Term: Muscular Dystrophies, Limb-Girdle - ID: D000002547 - Term: Cerebral Palsy - ID: D000009133 - Term: Muscular Atrophy - ID: D000009134 - Term: Muscular Atrophy, Spinal ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02244879 **Brief Title:** Effects of Resveratrol on Inflammation in Type 2 Diabetic Patients **Official Title:** Effects of Resveratrol on Inflammation in Type 2 Diabetic Patients. A Double-blind Randomized Controlled Trial #### Organization Study ID Info **ID:** RF-2010-2313155 #### Organization **Class:** OTHER **Full Name:** University of Turin, Italy ### Status Module #### Completion Date **Date:** 2016-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-03-08 **Type:** ESTIMATED **Last Update Submit Date:** 2016-03-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-02 **Type:** ACTUAL #### Start Date **Date:** 2013-10 **Status Verified Date:** 2016-03 #### Study First Post Date **Date:** 2014-09-19 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-15 **Study First Submit QC Date:** 2014-09-17 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Ministry of Health, Italy #### Lead Sponsor **Class:** OTHER **Name:** University of Turin, Italy #### Responsible Party **Investigator Affiliation:** University of Turin, Italy **Investigator Full Name:** Simona Bo **Investigator Title:** Dr **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This research will investigate the effect of resveratrol on inflammatory mediators in type 2 diabetic patients in vivo. The investigators will also investigate the hypothesis that resveratrol has an antioxidant activity, improves insulin sensitivity and lipid pattern, down-regulates bone-turnover. **Detailed Description:** Despite a large body of evidence demonstrating promising effects of resveratrol in rodents, human studies are still lacking and both preventive and therapeutic value of resveratrol in humans remains to be elucidated. The published evidence is not sufficiently strong to recommend for the administration of resveratrol to humans, beyond dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Furthermore, data are lacking either about safety during long-term administration, or on the efficacy of resveratrol administration in patients with chronic illnesses, such as diabetes mellitus. The main objective of this study is to investigate the effect of resveratrol on inflammatory mediators in type 2 diabetic patients in vivo. This research will investigate the hypothesis that resveratrol, when given orally to type 2 diabetic subjects for 24 weeks induces a decrease in values of high-sensitivity CRP (C-reactive protein) (primary outcome measure), IL-6 (Interleukin-6), PTX3 (pentraxin 3). The investigators will also investigate the hypothesis that resveratrol has an antioxidant activity, improves insulin sensitivity and lipid pattern, down-regulates bone-turnover. Secondary outcomes are therefore variations in the following variables: TAS (total antioxidant status), glycemia, glycated hemoglobin (HbA1c), Homeostasis model assessment of insulin resistance (HOMA-IR), total and HDL-cholesterol, triglycerides, adiponectin, body composition (evaluated by Dual-emission X-ray absorptiometry DXA-), bone mineral density (DXA). Finally, the investigators are interested in evaluating efficacy, safety and tolerability of two different dosages of resveratrol: 500 mg/day and 40 mg/day. ### Conditions Module **Conditions:** - Type 2 Diabetes Mellitus - Inflammation - Insulin Resistance - Other Disorders of Bone Density and Structure **Keywords:** - resveratrol - type 2 diabetes mellitus - inflammation - insulin resistance - body composition - bone mass ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 192 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In this arm, 64 patients will receive a tablet of placebo once/day for 6 months **Intervention Names:** - Dietary Supplement: resveratrol **Label:** placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** In this arm, 64 patients will receive a tablet of 40mg resveratrol once/day for 6 months **Intervention Names:** - Dietary Supplement: resveratrol **Label:** resveratrol 40 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** In this arm, 64 patients will receive a tablet of 500 mg resveratrol once/day for 6 months **Intervention Names:** - Dietary Supplement: resveratrol **Label:** resveratrol 500 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - placebo - resveratrol 40 - resveratrol 500 **Description:** arm resveratrol 500: 6 months of resveratrol 500 mg/day arm resveratrol 40: 6 months of resveratrol 40 mg/day **Name:** resveratrol **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Other Outcomes **Description:** To evaluate before-after change in bone mineral density and body composition by Dual-emission X-ray absorptiometry **Measure:** body composition and bone mineral density **Time Frame:** up to 25 months #### Primary Outcomes **Description:** To investigate changes from baseline in blood concentrations of high-sensitivity CRP after six months of treatment with either resveratrol at different dosages or placebo **Measure:** C reactive protein (CRP) **Time Frame:** up to 25 months #### Secondary Outcomes **Description:** To evaluate before-after changes in the concentrations of the following: Interleukin 6, Pentraxin-3, total antioxidant status, fasting glucose, insulin, glycated hemoglobin, total and HDL-cholesterol, triglycerides, adiponectin. **Measure:** Metabolic and oxidative markers **Time Frame:** up to 25 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. 35 years of age and older 2. Type 2 diabetes with body mass index (BMI)\<35 kg/m2 3. Subjects on hypoglycemic agents other than insulin 4. Willing to give written informed consent and able to understand, to participate in and to comply with the study requirements. Exclusion Criteria: 1. Subjects on any antioxidant medication 2. Patient on non-steroidal anti-inflammatory drug, steroids or insulin 3. On any agent with significant antioxidant properties 4. History of drug or alcohol abuse 5. Liver or kidney diseases 6. Any life threatening diseases 7. Allergy to peanuts, grapes, wine, mulberries 8. Pregnant women 9. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass surgery or coronary angioplasty) in the previous four Weeks 10. Subjects on anticoagulants **Maximum Age:** 85 Years **Minimum Age:** 35 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Turin **Country:** Italy **Facility:** University of Turin **State:** IT **Zip:** 10126 #### Overall Officials **Official 1:** **Affiliation:** University of Turin, Italy **Name:** Simona Bo, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Bo S, Togliatto G, Gambino R, Ponzo V, Lombardo G, Rosato R, Cassader M, Brizzi MF. Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a double-blind randomized controlled trial with resveratrol supplementation. Acta Diabetol. 2018 Apr;55(4):331-340. doi: 10.1007/s00592-017-1097-4. Epub 2018 Jan 12. **PMID:** 29330620 **Citation:** Bo S, Ponzo V, Evangelista A, Ciccone G, Goitre I, Saba F, Procopio M, Cassader M, Gambino R. Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial. Acta Diabetol. 2017 May;54(5):499-507. doi: 10.1007/s00592-017-0977-y. Epub 2017 Feb 25. **PMID:** 28238190 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000010335 - Term: Pathologic Processes - ID: D000006946 - Term: Hyperinsulinism - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BC05 - Name: Musculoskeletal Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: HIGH - As Found: Inflammation - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes Mellitus - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Type 2 Diabetes Mellitus - ID: M10370 - Name: Insulin Resistance - Relevance: HIGH - As Found: Insulin Resistance - ID: M5126 - Name: Bone Diseases - Relevance: HIGH - As Found: Disorder of Bone - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M9997 - Name: Hyperinsulinism - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001847 - Term: Bone Diseases - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 - ID: D000007333 - Term: Insulin Resistance - ID: D000007249 - Term: Inflammation ### Intervention Browse Module - Ancestors - ID: D000000975 - Term: Antioxidants - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000010975 - Term: Platelet Aggregation Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PlAggInh - Name: Platelet Aggregation Inhibitors ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M1684 - Name: Resveratrol - Relevance: HIGH - As Found: Avastin - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M13865 - Name: Platelet Aggregation Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077185 - Term: Resveratrol ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03183479 **Brief Title:** The Effects of Fibrinogen Concentrate Infusion on Blood Loss and Allogeneic Blood Conservation in Scoliosis Surgery **Official Title:** The Effects of Fibrinogen Concentrate Infusion on Perioperative Blood Loss and Allogeneic Blood Conservation in Patients Undergoing Scoliosis Surgery #### Organization Study ID Info **ID:** PUMCH-FC #### Organization **Class:** OTHER **Full Name:** Peking Union Medical College Hospital ### Status Module #### Completion Date **Date:** 2019-08-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-02 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-08-31 **Type:** ACTUAL #### Start Date **Date:** 2017-06-14 **Type:** ACTUAL **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2017-06-12 **Type:** ACTUAL **Study First Submit Date:** 2017-06-05 **Study First Submit QC Date:** 2017-06-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Peking Union Medical College Hospital #### Responsible Party **Investigator Affiliation:** Peking Union Medical College Hospital **Investigator Full Name:** Weiyun Chen **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Allogeneic blood products transfusions are often necessary to treat perioperative bleeding in patients undergoing complex scoliosis surgeries. A prospective, randomized trial is designed to evaluate if the infusion of fibrinogen concentrate may reduce allogeneic blood transfusion in patients undergoing scoliosis surgery. Eligible patients will be randomly assigned to treatment group (fibrinogen concentrate infusion) and control group (normal saline infusion), and functional fibrinogen will be measured to guide the infusion of fibrinogen concentrate. Perioperative blood loss, intraoperative blood loss, and the amount of perioperative allogeneic blood transfusion will be compared between the two groups to determine the effect of fibrinogen concentrate infusion. **Detailed Description:** This is a prospective, randomized, double-blinded, placebo controlled trial to evaluate the effects of fibrinogen concentrate infusion on perioperative blood loss and the amount of perioperative allogeneic blood transfusion in patients undergoing scoliosis surgery. Recently, the inherent risks of blood, along with the continued rise in blood costs, activated the development and use of alternatives to blood transfusion. Fibrinogen concentrate may limit postoperative bleeding and lead to a significant reduction in allogeneic blood products transfusions in cardiac surgery and craniosynostosis surgery. However, the effect of fibrinogen concentrate in scoliosis surgery is still uncertain. Therefore, a prospective, randomized trial is designed to evaluate if the infusion of fibrinogen concentrate may reduce allogeneic blood transfusion in patients undergoing scoliosis surgery. Patients older than 12y/o with adolescent idiopathic scoliosis planed for elective posterior scoliosis correction surgery will be enrolled for this study after informed consent. Patients will be randomly assigned to a treatment group or a control group. Functional fibrinogen will be measured using TEG 5000 (Haemoscope Corp, IL, USA) at the start of surgery and the results of FLEV and MA will be recorded. After pedicle screw placement, a second functional fibrinogen will be measured and the patients in treatment group will receive fibrinogen concentrate (FIBRORAAS, Shanghai RAAS Blood Products Co, Ltd, Shanghai, China) 30mg kg-1. For safety concern, the maximum fibrinogen concentrate administration for each individual shall not exceed either 2g. Patients in the control group will receive placebo treatment with normal saline. After 15 minutes from fibrinogen concentrate or placebo administration, a third functional fibrinogen measurement will be performed to assess the effect of treatment. The following treatment will be guaranteed by the standard protocol in the presence of ongoing bleeding. Data includes all the demographics, preoperative conditions, procedure details, intraoperative data, and outcome measurements will be recorded. Additional data including FLEV and MA value, as well as fibrinogen values both preoperatively and at the arrival at wards. The primary endpoint of this study will be the total perioperative blood loss, and secondary endpoints will include: perioperative blood loss per fused level, intraoperative blood loss per fused level, the amount of postoperative drainage, the amount of postoperative drainage per fused level, total units of perioperative allogeneic pRBCs transfused, total volume of FFP transfused, total PLT units transfused. Safety endpoints will include operative mortality and perioperative thromboembolic complications. ### Conditions Module **Conditions:** - Scoliosis; Adolescence - Bleeding - Surgery **Keywords:** - adolescent idiopathic scoliosis - fibrinogen concentrate - perioperative blood loss - transfusion ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Masking Description:** After randomization, the unblinded independent investigator will be in charge of fibrinogen concentrate (drug) or placebo preparation, which will be performed in a laboratory next to the operating room. When the patient meets the inclusion criteria and is enrolled in the study, the functional fibrinogen tests will be done in the same laboratory by the same researcher, and drug or placebo will be prepared in sterile bags with opaque covers afterwards. Fibrinogen concentrate will be diluted in 100mL of sterile water or an equivalent volume of 0.9% saline solution as placebo and will be delivered to the operating room by the investigator. The anesthesiologists, the surgical staff, and the patients will all be blinded. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 102 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patients in treatment group will receive Fibrinogen Concentrate Human administration. **Intervention Names:** - Drug: Fibrinogen Concentrate Human **Label:** Treatment group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The patients in control group will be administered with normal saline solution as placebo. **Intervention Names:** - Drug: Normal saline **Label:** Control group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment group **Description:** After start of surgery when all pedicle screws are placed, the patients in treatment group will receive fibrinogen concentrate 30mg kg-1. For safety concern, functional fibrinogen will be measured and the maximum fibrinogen concentrate administration for each individual shall not exceed 2g. Fibrinogen concentrate will be diluted in 100mL of sterile water and then be administered to patients. **Name:** Fibrinogen Concentrate Human **Other Names:** - FIBRORAAS **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Control group **Description:** 100mL normal saline will be administered to patients in control group as placebo **Name:** Normal saline **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** the total amount of intraoperative and postoperative blood loss **Measure:** Perioperative blood loss **Time Frame:** hospital stay up to 30 days #### Secondary Outcomes **Description:** amount of intraoperative and postoperative blood loss divided by the number of surgical fused levels **Measure:** Perioperative blood loss per fused level **Time Frame:** hospital stay up to 30 days **Description:** the amount of intraoperative blood loss **Measure:** Intraoperative blood loss **Time Frame:** From the time of skin incision until wound closure, assessed up to 12 hours **Description:** amount of intraoperative blood loss divided by the number of surgical fused levels **Measure:** Intraoperative blood loss per fused level **Time Frame:** From the time of skin incision until wound closure, assessed up to 12 hour **Description:** the amount of postoperative drainage **Measure:** Postoperative drainage **Time Frame:** hospital stay up to 30 days **Description:** amount of postoperative drainage divided by the number of surgical fused levels **Measure:** Postoperative drainage per fused level **Time Frame:** hospital stay up to 30 days **Description:** total units of RBC transfused perioperatively **Measure:** Perioperative allogeneic red blood cell (RBC) transfusion **Time Frame:** hospital stay up to 30 days **Description:** total volume of plasma transfused perioperatively **Measure:** Perioperative plasma transfusion **Time Frame:** hospital stay up to 30 days **Description:** total units of platelets transfused perioperatively **Measure:** Perioperative platelets transfusion **Time Frame:** hospital stay up to 30 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * patients diagnosed as adolescent idiopathic scoliosis * planed for elective posterior scoliosis correction surgery at Peking Union Medical College Hospital Exclusion Criteria: * preoperative anemia * preoperative congenital or acquired coagulopathy * ongoing anticoagulation therapy or drug intake that could cause bleeding * clinical signs or diagnosis of acute thromboembolism * emergency surgery * redo surgery **Maximum Age:** 18 Years **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** Peking Union Medical College Hospital **State:** Beijing **Zip:** 100730 #### Overall Officials **Official 1:** **Affiliation:** Peking Union Medical College Hospital **Name:** Weiyun Chen, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Data would only be shared with IRB approved collaborators. **Description:** Coded data is anticipated to be shared with potential collaborators. **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** Anticipated that data from the study will become available within 5 years after publication of main data. ### References Module #### References **Citation:** Chen W, Shen J, Zhang Y, Hu A, Liang J, Ma L, Yu X, Huang Y. A randomised controlled trial of fibrinogen concentrate during scoliosis surgery. Anaesthesia. 2020 Nov;75(11):1476-1481. doi: 10.1111/anae.15124. Epub 2020 Jun 4. **PMID:** 32500569 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013121 - Term: Spinal Curvatures - ID: D000013122 - Term: Spinal Diseases - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Blood Loss - ID: M15417 - Name: Scoliosis - Relevance: HIGH - As Found: Scoliosis - ID: M15918 - Name: Spinal Curvatures - Relevance: LOW - As Found: Unknown - ID: M15919 - Name: Spinal Diseases - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012600 - Term: Scoliosis - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02497079 **Brief Title:** Diagnostic Accuracy of Polymerase Chain Reaction for Mycobacterium Tuberculosis Using EBUS-TBNA Samples **Official Title:** Comparison of the Diagnostic Accuracy of Nested and Real-time Polymerase Chain Reaction for Mycobacterium Tuberculosis Using EBUS-TBNA Samples in Patients With Isolated Intrathoracic Lymphadenopathy #### Organization Study ID Info **ID:** PNUH-P-1 #### Organization **Class:** OTHER **Full Name:** Pusan National University Hospital ### Status Module #### Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2015-07-20 **Type:** ESTIMATED **Last Update Submit Date:** 2015-07-16 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Start Date **Date:** 2015-07 **Status Verified Date:** 2015-07 #### Study First Post Date **Date:** 2015-07-14 **Type:** ESTIMATED **Study First Submit Date:** 2015-07-08 **Study First Submit QC Date:** 2015-07-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Pusan National University Hospital #### Responsible Party **Investigator Affiliation:** Pusan National University Hospital **Investigator Full Name:** Jung Seop Eom **Investigator Title:** Clinical Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to compare the diagnostic efficacy of nested and realtime polymerase chain reaction for Mycobacterium tuberculosis using EBUS-TBNA samples in patients with isolated intrathoracic lymphadenopathy. **Detailed Description:** Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used to perform mediastinal lymph node sampling, little information is available on polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA samples in patients with isolated intrathoracic lymphadenopathy. In addition, two methods of TB-PCR (nested PCR and realtime PCR) are available for the detection of Mycobacterium tuberculosis and which method is superior for detection of Mycobacterium tuberculosis has not been established in patients with isolated intrathoracic lymphadenopathy. Thus, this study was design to compare the diagnostic efficacy of nested and realtime TB-PCR using EBUS-TBNA samples in patients with isolated intrathoracic lymphadenopathy in South Korea, where the incidence of tuberculosis is intermediate (97/100,000 per year). ### Conditions Module **Conditions:** - Lymphadenopathy - Tuberculosis - Sarcoidosis **Keywords:** - Bronchoscopy - Ultrasonography - Tuberculous lymphadenitis - Polymerase chain reaction - Sensitivity and specificity ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In all patients, nested polymerase chain reaction for Mycobacterium tuberculosis is performed with formalin-fixed paraffin-embedded specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration. **Intervention Names:** - Device: Nested PCR for formalin-fixed tissues **Label:** Nested PCR for formalin-fixed tissues **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** In all patients, nested polymerase chain reaction for Mycobacterium tuberculosis is performed with specimens in sterile saline obtained by endobronchial ultrasound-guided transbronchial needle aspiration. **Intervention Names:** - Device: Nested PCR for fresh tissues **Label:** Nested PCR for fresh tissues **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** In all patients, real-time polymerase chain reaction for Mycobacterium tuberculosis is performed with specimens in sterile saline obtained by endobronchial ultrasound-guided transbronchial needle aspiration. **Intervention Names:** - Device: Real-time PCR for fresh tissues **Label:** Real-time PCR for fresh tissues **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Nested PCR for formalin-fixed tissues **Description:** For nested PCR, formalin-fixed paraffin-embedded tissues were incubated in 1 mL of xylene at 60°C for 30 min and then centrifuged for 10 min. Paraffin and the supernatant were removed from the samples after centrifugation. The same procedures were repeated until deparaffinization was complete. After adding 1 mL of alcohol, the samples were centrifuged for 5 min, and the supernatant was removed. The sample was then air-dried as a pellet. DNA was extracted using QIAamp (Qiagen, Valencia, CA, USA). PCR amplifications were performed using Mycobacterium tuberculosis IS6110 primers. The first round using outer primers and the second round using inner primers amplified a 256- and 181-bp fragment, respectively. Finally, the PCR products were visualized in a 2% agarose gel. **Name:** Nested PCR for formalin-fixed tissues **Other Names:** - MTB-PCR kit; Biosewoom, Seoul, South Korea **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Nested PCR for fresh tissues **Description:** For nested PCR with specimens in sterile saline, DNA was extracted using QIAamp (Qiagen, Valencia, CA, USA). PCR amplifications were performed using Mycobacterium tuberculosis IS6110 primers. The first round using outer primers and the second round using inner primers amplified a 256- and 181-bp fragment, respectively. Finally, the PCR products were visualized in a 2% agarose gel. **Name:** Nested PCR for fresh tissues **Other Names:** - MTB-PCR kit; Biosewoom, Seoul, South Korea **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Real-time PCR for fresh tissues **Description:** For real-time PCR, specimens in sterile saline were filtered and 1 mL of phosphate based saline was added. After centrifugation for 3 min, the supernatant was removed. Next, 50 μL of extraction buffer was added to the sample, and the sample was heated at 100°C for 20 min. After centrifugation for 3 min, the supernatant was used in PCR. Real-time PCR was performed using the AdvanSure TB/NTM real-time PCR kit. Three channels were used in the real-time PCR reaction (Mycobacterium tuberculosis complex, mycobacteria, and internal control). Signals for FAM, HEX, and Cy5 were measured in each channel. Mycobacterium tuberculosis was considered present if the cycle threshold of rpoB was less than 35 on each signal and greater than or equivalent to that of IS6110. **Name:** Real-time PCR for fresh tissues **Other Names:** - AdvanSure TB/NTM real-time PCR kit; LG, Seoul, South Korea **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** In all participants with isolated intrathoracic lymphadenopathy, three modalities of TB-PCR (nested PCR for formalin-fixed paraffin-embedded tissues, nested PCR for fresh tissues and real-time PCR for fresh tissues) are performed using EBUS-TBNA samples. The numbers of participants who reported as positive for each TB-PCR modalities are collected. From these data, sensitivity, specificity and diagnostic accuracy of each TB-PCR modalities to diagnose tuberculous lymphadenitis will be calculated. **Measure:** Number of participants who detected each polymerase chain reactions for Mycobacterium tuberculosis **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with isolated intrathoracic lymphadenopathy Exclusion Criteria: * Suspicion of primary lung cancer on CT or PET scan * Suspicion of pulmonary tuberculosis on CT or PET scan * Suspicion of sarcoidosis of lung parenchyma on CT or PET scan **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** ejspulm@gmail.com **Name:** Jung Seop Eom Eom, Master **Phone:** 82-01-2081-0859 **Role:** CONTACT #### Locations **Location 1:** **City:** Busan **Contacts:** ***Contact 1:*** - **Email:** ejspulm@gmail.com - **Name:** Jung Seop Eom, Master - **Phone:** +821020810859 - **Role:** CONTACT ***Contact 2:*** - **Email:** mokgamokga@gmail.com - **Name:** Jeong Ha Mok, Master - **Phone:** +820185196183 - **Role:** CONTACT **Country:** Korea, Republic of **Facility:** Pusan National University Hospital **Status:** RECRUITING **Zip:** 602-739 #### Overall Officials **Official 1:** **Affiliation:** Pusan National University Hospital **Name:** Jeong Ha Mok, Master **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Pusan National University Hospital **Name:** Jung Seop Eom, Master **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Navani N, Lawrence DR, Kolvekar S, Hayward M, McAsey D, Kocjan G, Falzon M, Capitanio A, Shaw P, Morris S, Omar RZ, Janes SM; REMEDY Trial Investigators. Endobronchial ultrasound-guided transbronchial needle aspiration prevents mediastinoscopies in the diagnosis of isolated mediastinal lymphadenopathy: a prospective trial. Am J Respir Crit Care Med. 2012 Aug 1;186(3):255-60. doi: 10.1164/rccm.201203-0393OC. Epub 2012 May 31. **PMID:** 22652031 **Citation:** Navani N, Molyneaux PL, Breen RA, Connell DW, Jepson A, Nankivell M, Brown JM, Morris-Jones S, Ng B, Wickremasinghe M, Lalvani A, Rintoul RC, Santis G, Kon OM, Janes SM. Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study. Thorax. 2011 Oct;66(10):889-93. doi: 10.1136/thoraxjnl-2011-200063. Epub 2011 Aug 3. **PMID:** 21813622 **Citation:** Sun J, Teng J, Yang H, Li Z, Zhang J, Zhao H, Garfield DH, Han B. Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing intrathoracic tuberculosis. Ann Thorac Surg. 2013 Dec;96(6):2021-7. doi: 10.1016/j.athoracsur.2013.07.005. Epub 2013 Sep 12. **PMID:** 24035300 **Citation:** Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999 Aug;160(2):736-55. doi: 10.1164/ajrccm.160.2.ats4-99. No abstract available. **PMID:** 10430755 **Citation:** Bezabih M, Mariam DW, Selassie SG. Fine needle aspiration cytology of suspected tuberculous lymphadenitis. Cytopathology. 2002 Oct;13(5):284-90. doi: 10.1046/j.1365-2303.2002.00418.x. **PMID:** 12421444 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009164 - Term: Mycobacterium Infections - ID: D000000193 - Term: Actinomycetales Infections - ID: D000016908 - Term: Gram-Positive Bacterial Infections - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000006968 - Term: Hypersensitivity, Delayed - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC01 - Name: Infections - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M994 - Name: Lymphadenopathy - Relevance: HIGH - As Found: Lymphadenopathy - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M12119 - Name: Mycobacterium Infections - Relevance: LOW - As Found: Unknown - ID: M17127 - Name: Tuberculosis - Relevance: HIGH - As Found: Tuberculosis - ID: M15325 - Name: Sarcoidosis - Relevance: HIGH - As Found: Sarcoidosis - ID: M17138 - Name: Tuberculosis, Lymph Node - Relevance: LOW - As Found: Unknown - ID: M11196 - Name: Lymphadenitis - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M19252 - Name: Gram-Positive Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10019 - Name: Hypersensitivity, Delayed - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014376 - Term: Tuberculosis - ID: D000012507 - Term: Sarcoidosis - ID: D000072281 - Term: Lymphadenopathy ### Intervention Browse Module - Ancestors - ID: D000004202 - Term: Disinfectants - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M3777 - Name: Ethanol - Relevance: LOW - As Found: Unknown - ID: M8681 - Name: Formaldehyde - Relevance: HIGH - As Found: Encephalomyelitis - ID: M7383 - Name: Disinfectants - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000005557 - Term: Formaldehyde ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02408679 **Brief Title:** Predictive Questionnaire for Vitamin D Insufficiency in Healthy Adults **Official Title:** A Study to Validate a Predictive Questionnaire for Vitamin D Insufficiency in Healthy Adults #### Organization Study ID Info **ID:** 14-035 #### Organization **Class:** INDUSTRY **Full Name:** Lesieur #### Secondary ID Infos **Domain:** ANSM **ID:** ID-RCB Number : 2014-A01633-44 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2015-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-04-03 **Type:** ESTIMATED **Last Update Submit Date:** 2015-03-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-02 **Type:** ACTUAL #### Start Date **Date:** 2015-01 **Status Verified Date:** 2015-03 #### Study First Post Date **Date:** 2015-04-03 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-05 **Study First Submit QC Date:** 2015-03-31 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Naturalpha #### Lead Sponsor **Class:** INDUSTRY **Name:** Lesieur #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this clinical study is to evaluate the metrological properties of a questionnaire that aims to identify the vitamin D status in reference to a vitamin D blood dosage. **Detailed Description:** Each subject will perform only one visit (visit V1). The study duration per subject will last about 2 hours. During this visit V1, the subjects will perform a medical exam in order to check their eligibility (general statement and check of inclusion / non-inclusion criteria). The eligible subjects will fill up a study questionnaire and will perform a blood sampling for a dosage of serum vitamin D. ### Conditions Module **Conditions:** - Healthy Volunteers **Keywords:** - Vitamin D - Vitamin D Deficiency - Vitamin D Insufficiency - Healthy adults - Predictive questionnaire ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 300 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 300 eligible subjects will perform a blood sampling for a dosage of serum vitamin D and will fill up a study questionnaire during one visit. **Intervention Names:** - Procedure: Blood sampling - Other: Predictive questionnaire for vitamin D insufficiency **Label:** All subjects ### Interventions #### Intervention 1 **Arm Group Labels:** - All subjects **Description:** One blood sampling will be performed for a serum vitamin D dosage. The volume of blood collected will not exceed 4 ml. **Name:** Blood sampling **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - All subjects **Description:** The questionnaire includes 19 questions concerning the following topics : a) sun exposure, b) living situation, c) eating habits and Vitamin D dietary intakes. In addition, two questions will capture demographic data. **Name:** Predictive questionnaire for vitamin D insufficiency **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Evaluation of the internal coherence and factorial structure of the questionnaire, establishment of scoring rules **Measure:** Questionnaire internal validity **Time Frame:** Day 1 **Description:** Prediction of the vitamin D status (threshold value, sensitivity, specificity for vitamin D insufficiency; threshold value, sensitivity, specificity for vitamin D deficiency) **Measure:** Questionnaire external validity **Time Frame:** Day 1 **Description:** Interests for coupling the study questionnaire and demographic data (age, gender, Body Mass Index, phototype). **Measure:** Confounding factors (demographic data) **Time Frame:** Day 1 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male and female volunteers * Subject able to communicate with the investigator and the study team, able to read and write and follow all study instructions. * Written informed consent provided and signed prior screening, after receiving and understanding the subject information. * Registered with the French Social Security, in agreement with the French law on biomedical experimentation. Exclusion Criteria: * Subject with diagnosed osteoporosis, osteopenia or osteomalacia. * Subject with known disease that contributes in osteoporosis: Rheumatoid arthritis, Malabsorption syndrome, Inflammatory bowel disease, Hyperthyroidism, Hyperparathyroidism. * Subject with known hepatic impairment. * Subject with known liver impairment or with a history of renal transplantation. * Subject with history of cancer. * Subject with history of bariatric surgery. * Subject taking or having taken osteoporosis inducing treatment, or treatment with an effect on calcium and phosphorus metabolism during the 3 months prior the visit: Corticosteroids, Enzyme inducing anticonvulsants, Heparin. * Subject requiring vitamin D supplementation for a diagnosed pathology. * Pregnant or breastfeeding Female. * Subject with history of alcohol or drug abuse. * Participation to any other clinical trial simultaneously and/or not having ended the exclusion period of another clinical trial. * Subject of legal age unable of giving consent. * Subject deprived of liberty by judicial or administrative decision. * Subject of legal age under legal protection. * Subject having received over 4500 Euros for clinical trial participation within the prior year including the indemnity for the present study. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Healthy Volunteers ### Contacts Locations Module #### Locations **Location 1:** **City:** Lille **Country:** France **Facility:** Clinical Nutrition Center Naturalpha (CNCN) **Zip:** 59020 #### Overall Officials **Official 1:** **Affiliation:** Lesieur, France **Name:** Sylvie BRETON, R&D Innovation Manager **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Clinical Nutrition Center Naturalpha, France **Name:** Xavier Deplanque, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M17551 - Name: Vitamin D Deficiency - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000050071 - Term: Bone Density Conservation Agents ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: HIGH - As Found: Ultrasound - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: T442 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: T479 - Name: Vitamin D3 - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014807 - Term: Vitamin D ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03115879 **Brief Title:** The Effect High Velocity Low Amplitude Hip Mobilization on Strength in Subjects With Lower Extremity Pathology **Official Title:** The Effect of High Velocity Low Amplitude Hip Mobilization on Strength in Subjects With Lower Extremity Pathology #### Organization Study ID Info **ID:** DFreitas #### Organization **Class:** OTHER **Full Name:** Faculdade de Ciências Médicas da Santa Casa de São Paulo ### Status Module #### Completion Date **Date:** 2016-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-04-14 **Type:** ACTUAL **Last Update Submit Date:** 2017-04-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-03 **Type:** ACTUAL #### Start Date **Date:** 2015-02 **Type:** ACTUAL **Status Verified Date:** 2017-03 #### Study First Post Date **Date:** 2017-04-14 **Type:** ACTUAL **Study First Submit Date:** 2017-03-23 **Study First Submit QC Date:** 2017-04-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Faculdade de Ciências Médicas da Santa Casa de São Paulo #### Responsible Party **Investigator Affiliation:** Faculdade de Ciências Médicas da Santa Casa de São Paulo **Investigator Full Name:** Diego Galace de Freitas **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Introduction: Lower extremity weakness associated with musculoskeletal pathology can cause activity limitations. Physical therapy intervention in the form of exercise is commonly directed at improving muscular performance, however, neuromuscular adaptations may limit the effectiveness of traditional strengthening exercises. Manual therapy techniques have been used as a disinhibitory intervention to increase muscle activation and strength before participating in strengthening exercises or performing functional tasks While there is recent evidence to support joint mobilization as a valuable manual therapy disinhibitory intervention Currently, there is no evidence to substantiate anecdotal experience that a HVLAT hip distraction mobilization improves muscle performance in subjects with lower extremity pathology and lower extremity weakness. The purpose of this study was to determine if a HVLAT hip distraction mobilization would result in an immediate change of maximal force output of the quadriceps, gluteus maximus and gluteus medius. Methods: Forty individuals with a lower extremity pathology volunteered for this study. Inclusion criteria were having a unilateral musculoskeletal pathology, being greater than 18 years of age, 10% decrease in muscle strength in symptomatic side compared to healthy side, and absence of medical precautions that would prevent a maximal effort strength test and exclusion criteria included individuals with a history lower extremity recent muscle or tendon ruptures (within the past 6 months) and postoperative knee, hip and ankle surgery. Demographic data, including diagnosis from referring physician were collected. All subjects completed the Lower extremity function scale (LEFS). A single evaluator blinded to the involved extremity was responsible for quadriceps, gluteus medius and maximus strength analysis pre and post mobilization of both symptomatic and non-symptomatic sides. The subject underwent the HVLAT hip distraction mobilization of the symptomatic side, and an immediate re-assessment of strength of both symptomatic and non-symptomatic sides followed the mobilization. ### Conditions Module **Conditions:** - Hip Joint - Muscle Weakness ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Hip manipulation simulation **Intervention Names:** - Other: Hip manipulation simulation **Label:** Placebo Group **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Hip manipulation **Intervention Names:** - Other: Hip mobilization **Label:** Manipulation Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Manipulation Group **Description:** High velocity low amplitude hip mobilization of the experimental group **Name:** Hip mobilization **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Placebo Group **Description:** Hip manipulation simulation **Name:** Hip manipulation simulation **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** A Lafayette dynamometer was used to evaluate the maximum isometric torque of the muscles **Measure:** Muscle strength **Time Frame:** Assessment of muscle strength was performed after 10 minutes of manipulation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Individuals with a lower extremity pathology volunteered for this study * Being greater than 18 years of age * 10% decrease in muscle strength in symptomatic side compared to healthy side * Absence of medical precautions that would prevent a maximal effort strength test. Exclusion Criteria: * Included individuals with a history lower extremity arthroplasty. * Recent muscle or tendon ruptures (within the past 6 months) * Unhealed fractures * Neurological diseases * Malignant cancer * Osteoporosis * Active infections processes * Early postoperative knee, hip and ankle surgery with range of motion and weight bearing restrictions. **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000020879 - Term: Neuromuscular Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M20944 - Name: Muscle Weakness - Relevance: HIGH - As Found: Muscle Weakness - ID: M13204 - Name: Paresis - Relevance: LOW - As Found: Unknown - ID: M4554 - Name: Asthenia - Relevance: LOW - As Found: Unknown - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M22619 - Name: Neuromuscular Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018908 - Term: Muscle Weakness ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02695979 **Brief Title:** Changes of Macrophage Migration Inhibitory Factor During Orthotopic Liver Transplantation **Official Title:** Changes of Macrophage Migration Inhibitory Factor and Thyroid Hormones During Liver Transplantation. Association With Graft Dysfunction #### Organization Study ID Info **ID:** 1458/2014 #### Organization **Class:** OTHER **Full Name:** Medical University of Vienna ### Status Module #### Completion Date **Date:** 2019-08 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2018-03-01 **Type:** ACTUAL **Last Update Submit Date:** 2018-02-28 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-09 **Type:** ESTIMATED #### Start Date **Date:** 2014-08 **Status Verified Date:** 2018-02 #### Study First Post Date **Date:** 2016-03-02 **Type:** ESTIMATED **Study First Submit Date:** 2016-01-12 **Study First Submit QC Date:** 2016-02-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Medical University of Vienna #### Responsible Party **Investigator Affiliation:** Medical University of Vienna **Investigator Full Name:** Dr. Joanna Stefaniak **Investigator Title:** Dr.med. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Collecting blood, graft liver effluent and urine samples from patients undergoing orthotopic liver transplantation. **Detailed Description:** Aims are to measure Macrophage Migration Inhibitory Factor, Macrophage Migration Inhibitory Factor II and its' soluble receptor CD74 in serum, liver graft effluent and urine in and evaluate MIF's role in hepatic ischemia/reperfusion injury, postoperative graft function and kidney function. ### Conditions Module **Conditions:** - Evidence of Liver Transplantation ### Design Module #### Bio Spec **Description:** Blood, graft liver effluent, urine samples **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients aged 18-70 with end-stage liver disease undergoing orthotopic liver transplantation (OLT). **Label:** Patients undergoing OLT ### Outcomes Module #### Other Outcomes **Description:** Acute kidney injury, outcome **Measure:** Acute kidney injury, outcome **Time Frame:** 48 months #### Primary Outcomes **Measure:** Macrophage Migration Inhibitory Factor in human serum, liver graft effluent and urine **Time Frame:** 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * End stage liver disease, chronic liver failure, orthotopic liver transplantation Exclusion Criteria: * Combined transplantations (liver plus kidney or lung), age under 18 y, acute liver failure **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients undergoing orthotopic liver transplantation ### Contacts Locations Module #### Locations **Location 1:** **City:** Vienna **Country:** Austria **Facility:** Medical University Vienna **Zip:** 1090 #### Overall Officials **Official 1:** **Affiliation:** Medical University Vienna, Department of Anesthesia, General Intensive Care and Pain Management **Name:** Peter Faybik, Prof **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M16718 - Name: Thyroid Diseases - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics ### Intervention Browse Module - Browse Leaves - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00398879 **Brief Title:** Placebo-Controlled Study of Perifosine + Single Agent Chemotherapy for Metastatic Cancer Patients **Official Title:** A Randomized Placebo-Controlled Study of Perifosine in Combination With Single Agent Chemotherapy for Metastatic Cancer Patients #### Organization Study ID Info **ID:** Perifosine 211 #### Organization **Class:** INDUSTRY **Full Name:** AEterna Zentaris ### Status Module #### Completion Date **Date:** 2011-10 **Type:** ACTUAL #### Disp First Post Date **Date:** 2018-03-14 **Type:** ACTUAL **Disp First Submit Date:** 2018-03-12 **Disp First Submit QC Date:** 2018-03-12 #### Expanded Access Info #### Last Update Post Date **Date:** 2018-03-14 **Type:** ACTUAL **Last Update Submit Date:** 2018-03-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-12 **Type:** ACTUAL #### Start Date **Date:** 2005-08 **Status Verified Date:** 2012-02 #### Study First Post Date **Date:** 2006-11-14 **Type:** ESTIMATED **Study First Submit Date:** 2006-11-06 **Study First Submit QC Date:** 2006-11-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** AEterna Zentaris #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an exploratory phase 2, randomized placebo-controlled trial with stratification for disease and chemotherapy type. The study is subsequently closed to enrollment in all arms except patients with metastatic colorectal cancer which would be randomized to either capecitabine plus perifosine or capecitabine alone. The effects of perifosine may be manifested by increased time to progression, tumor regression reflected in partial or complete responses, or a combination of these outcomes. The primary goal of this trial is to obtain a preliminary and objective assessment of the effects of perifosine on time to progression. **Detailed Description:** This is an exploratory phase 2, randomized placebo-controlled trial with stratification for disease and chemotherapy type. If there is any evidence of improved time to progression in any tumor type with any of the drugs to be evaluated, the initial study or component(s) of the study will be expanded to increase the certainty that this is an effect of perifosine. If there is compelling evidence of benefit from this study, a phase 3 trial will be conducted to obtain proof of principle. Primary Study Objectives: To determine the time to tumor progression when receiving single agent chemotherapy (capecitabine) in combination with perifosine in comparison to patients receiving single agent chemotherapy (capecitabine) alone (i.e., with placebo). Secondary Study Objectives: * To determine the toxicity of single agent chemotherapy in combination with perifosine. * To compare the time to progression of chemotherapy in combination with placebo to historical experience. * Overall survival will also be evaluated. ### Conditions Module **Conditions:** - Colon Cancer **Keywords:** - Capecitabine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 381 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Perifosine 50 mg/d qd + Capecitabine 825 mg/m\^2 BID days 1 - 14 q 3 weeks until progression **Intervention Names:** - Drug: Perifosine - Drug: Capecitabine **Label:** Arm 1: Perifosine + Capecitabine **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Perifosine Placebo 50 mg/d qd + Capecitabine 825 mg/m\^2 BID days 1 - 14 q 3 weeks until progression **Intervention Names:** - Drug: Capecitabine - Other: Perifosine Placebo **Label:** Arm 2: Perifosine Placebo + Capecitabine **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm 1: Perifosine + Capecitabine **Description:** Perifosine 50 mg/d qd **Name:** Perifosine **Other Names:** - D-21266 - KRX-0401 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Arm 1: Perifosine + Capecitabine - Arm 2: Perifosine Placebo + Capecitabine **Description:** Capecitabine 825 mg/m\^2 BID days 1 - 14 q 3 weeks **Name:** Capecitabine **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Arm 2: Perifosine Placebo + Capecitabine **Description:** Placebo to Perifosine 50 mg/d qd **Name:** Perifosine Placebo **Other Names:** - placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Time to progression will be measured from the first day of study drug until progression. **Measure:** Effects of perifosine on time to progression **Time Frame:** Every 12 weeks #### Secondary Outcomes **Description:** Determination of the toxicity of single agent chemotherapy in combination with perifosine. Toxicity evaluation is to be performed throughout the study. **Measure:** Toxicity **Time Frame:** Every 12 weeks **Description:** To compare the time to progression of chemotherapy in combination with placebo to historical experience. **Measure:** Comparison of time to progression to historical experience **Time Frame:** Every 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. In the opinion of the treating physician, treatment with one of the following regimens should represent an appropriate treatment for the patient. - Capecitabine 825 mg/m2 BID days 1 - 14 q 3 weeks 2. Patients should have a histologically or cytologically confirmed diagnosis of colorectal cancer. 3. Patients must have received at least one but no more than two prior chemotherapy regimen(s) for the treatment of metastatic or recurrent disease. 4. ECOG performance status 0 or 1. * Leukocytes \>= 4,000/μL * absolute neutrophil count \>= 1,500/ μL * platelets \>= 100,000/ μL * HCT \> 28% (with or without growth factor support) * Creatinine \<= 2.5 mg/dl * total bilirubin \< 1.5 x upper limit of normal * transaminase \< 2.5 x upper limit of normal 5. Patients must have recovered from acute toxicity-excluding alopecia-related to prior therapy, including surgery or radiotherapy. 6. Patients with brain metastases may be admitted, provided the disease has been treated and been stable for 2 months. 7. Patients must have ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. Patients receiving any other investigational agents or devices. 2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine). 3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness, or social situations that would limit compliance with study requirements. 4. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study due to potential pharmacokinetic interactions with perifosine. 5. Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), or New York Heart Assoc. class II - IV congestive heart failure. 6. Female patients who are pregnant or lactating are ineligible. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tucson **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Arizona **Zip:** 85704 **Location 2:** **City:** Beverly Hills **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 90211 **Location 3:** **City:** Deer Park **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 94574 **Location 4:** **City:** Monterey **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 93940 **Location 5:** **City:** Newport Beach **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 92663 **Location 6:** **City:** Pomona **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 91767 **Location 7:** **City:** Santa Rosa **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 95403 **Location 8:** **City:** Soquel **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 95703 **Location 9:** **City:** Stockton **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** California **Zip:** 95207 **Location 10:** **City:** Colorado Springs **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Colorado **Zip:** 80909 **Location 11:** **City:** Greeley **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Colorado **Zip:** 80631 **Location 12:** **City:** Middletown **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Connecticut **Zip:** 06457 **Location 13:** **City:** Norwich **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Connecticut **Zip:** 06360 **Location 14:** **City:** Aventura **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 33180 **Location 15:** **City:** Coral Springs **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 33065 **Location 16:** **City:** Lake City **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 32055 **Location 17:** **City:** Miami **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 33176 **Location 18:** **City:** Ormond Beach **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 32174 **Location 19:** **City:** Sebastian **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 32958 **Location 20:** **City:** Vero Beach **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Florida **Zip:** 32960 **Location 21:** **City:** Augusta **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Georgia **Zip:** 30904 **Location 22:** **City:** Lawrenceville **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Georgia **Zip:** 30045 **Location 23:** **City:** Marietta **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Georgia **Zip:** 30060 **Location 24:** **City:** Galesburg **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Illinois **Zip:** 61401 **Location 25:** **City:** Park Ridge **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Illinois **Zip:** 60068 **Location 26:** **City:** Louisville **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Kentucky **Zip:** 40202 **Location 27:** **City:** Lafayette **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Louisiana **Zip:** 70506 **Location 28:** **City:** Grand Rapids **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Michigan **Zip:** 49546 **Location 29:** **City:** Kalamazoo **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Michigan **Zip:** 49048 **Location 30:** **City:** Branson **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Missouri **Zip:** 65616 **Location 31:** **City:** Billings **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Montana **Zip:** 59103 **Location 32:** **City:** Great Falls **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Montana **Zip:** 59405 **Location 33:** **City:** Albany **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** New York **Zip:** 12208 **Location 34:** **City:** Armonk **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** New York **Zip:** 10504 **Location 35:** **City:** Great Neck **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** New York **Zip:** 11042 **Location 36:** **City:** Wilmington **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** North Carolina **Zip:** 28401 **Location 37:** **City:** Dayton **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Ohio **Zip:** 45409 **Location 38:** **City:** Pottsville **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Pennsylvania **Zip:** 17901 **Location 39:** **City:** Sayre **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Pennsylvania **Zip:** 18840 **Location 40:** **City:** Greenville **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** South Carolina **Zip:** 29605 **Location 41:** **City:** Chattanooga **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Tennessee **Zip:** 37404 **Location 42:** **City:** Memphis **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Tennessee **Zip:** 38120 **Location 43:** **City:** Dallas **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Texas **Zip:** 75231 **Location 44:** **City:** Dallas **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Texas **Zip:** 75246 **Location 45:** **City:** Tyler **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Texas **Zip:** 75702 **Location 46:** **City:** Chesapeake **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Virginia **Zip:** 23320 **Location 47:** **City:** Norfolk **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Virginia **Zip:** 23502 **Location 48:** **City:** Spokane **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Washington **Zip:** 99218 **Location 49:** **City:** Appleton **Country:** United States **Facility:** AOI Pharmaceuticals Investigative Site **State:** Wisconsin **Zip:** 54915 #### Overall Officials **Official 1:** **Affiliation:** Online Collaborative Oncology Group **Name:** Craig Henderson, MD **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Bendell JC, Nemunaitis J, Vukelja SJ, Hagenstad C, Campos LT, Hermann RC, Sportelli P, Gardner L, Richards DA. Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2011 Nov 20;29(33):4394-400. doi: 10.1200/JCO.2011.36.1980. Epub 2011 Oct 3. **PMID:** 21969495 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000009385 - Term: Neoplastic Processes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastatic Cancer - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M377 - Name: Capecitabine - Relevance: HIGH - As Found: Function - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069287 - Term: Capecitabine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05190679 **Brief Title:** Prospective Phenotyping for Genetic Subtypes of Early-onset Atrial Fibrillation **Official Title:** Prospective Phenotyping for Genetic Subtypes of Early-onset Atrial Fibrillation #### Organization Study ID Info **ID:** 210819 #### Organization **Class:** OTHER **Full Name:** Vanderbilt University Medical Center #### Secondary ID Infos **ID:** R01HL155197 **Link:** https://reporter.nih.gov/quickSearch/R01HL155197 **Type:** NIH ### Status Module #### Completion Date **Date:** 2026-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-05 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-02 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-04-27 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2022-01-13 **Type:** ACTUAL **Study First Submit Date:** 2021-12-28 **Study First Submit QC Date:** 2021-12-28 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Heart, Lung, and Blood Institute (NHLBI) #### Lead Sponsor **Class:** OTHER **Name:** Vanderbilt University Medical Center #### Responsible Party **Investigator Affiliation:** Vanderbilt University Medical Center **Investigator Full Name:** M. Benjamin Shoemaker **Investigator Title:** Assistant Professor of Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a prospective, case-control study that seeks to learn about the role of genetics in early onset atrial fibrillation (AF) and if genetic testing can be used to improve how the investigators treat atrial fibrillation. The study will enroll 225 participants. Eligible participants will have undergone sequencing for arrhythmia and cardiomyopathy (CM) genes. Based on those results, participants will be recruited for an outpatient research visit with testing that includes cardiac MRI, rest/stress/signal-averaged ECGs, and cardiac monitoring. If an inherited arrhythmia/CM syndrome is diagnosed, guideline-directed changes to medical care will be recommended. **Detailed Description:** This study will address the hypothesis that re-phenotyping patients with AF and pathogenic arrhythmia/CM variants will identify unrecognized underlying genetic disease. The investigators will recruit from participants sequenced as part of our prospective clinical registries and participants cared for in the Vanderbilt Genetic Arrhythmia Clinic or Meharry Arrhythmia Clinic and enrolled in the Vanderbilt Early-onset Atrial Fibrillation Registry (IRB #201666). Eligible participants will have pathogenic/likely pathogenic (P/LP) rare variants (or matched controls) and will undergo prospective cardiac phenotyping, which will include a cardiac MRI, rest/stress/signal averaged ECGs, blood work, and ambulatory ECG monitoring. A subset of patients will also undergo a procainamide drug challenge. If an inherited arrhythmia/CM syndrome is diagnosed, guideline-directed changes to medical care will be recommended. This study will define the cardiac phenotype of individuals with AF who have a P/LP rare variant in an inherited arrhythmia or CM disease gene and compare to controls. Participants with a P/LP variant in a cardiomyopathy gene or arrhythmia gene (N=150) will be compared to controls (N=75). Controls will have no P/LP variant and be balanced for sex, race, and ethnicity. The association between P/LP variants and the following endpoints will be tested: 1) imaging and ECG-derived measurements (e.g., ventricular size, function, fibrosis, ectopy); 2) diagnoses (e.g., arrhythmogenic cardiomyopathy (AC), hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), Long QT Syndrome (LQTS), Short QT Syndrome (SQTS), Brugada Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Progressive Cardiac Conduction Disease (PCCD); and 3) management changes including new medical therapy, activity restrictions, implantable cardioverter-defibrillator use, or cascade screening. Sample sizes per group have been selected to power the diagnostic and management endpoints. An Adjudication Committee with arrhythmia, CM, and genetics expertise will determine if diagnostic criteria are met and make management recommendations. ### Conditions Module **Conditions:** - Atrial Fibrillation **Keywords:** - Genetic disease ### Design Module #### Bio Spec **Description:** Whole blood samples retained for DNA extraction. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 225 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 6 Weeks ### Arms Interventions Module #### Arm Group 1 **Description:** Identified Pathogenic/Likely pathogenic rare variant in cardiomyopathy (CM) gene which include inherited CM syndromes. **Intervention Names:** - Other: None/Observational Studies **Label:** Cardiomyopathy Rare Variant Cases #### Arm Group 2 **Description:** Identified Pathogenic/Likely pathogenic rare variant in arrhythmia genes. **Intervention Names:** - Other: None/Observational Studies **Label:** Arrhythmia Rare Variant Cases #### Arm Group 3 **Description:** No rare variant in CM, arrhythmia, or other atrial fibrillation gene. **Intervention Names:** - Other: None/Observational Studies **Label:** Controls ### Interventions #### Intervention 1 **Arm Group Labels:** - Arrhythmia Rare Variant Cases - Cardiomyopathy Rare Variant Cases - Controls **Description:** This is an observational study and there is no intervention. **Name:** None/Observational Studies **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Clinical data and results are reviewed by the Adjudication Committee to determine if criteria for diagnostic endpoints are met for each participant that has completed the phenotyping protocol. The committee will remain blinded to the participant's genotype until the discussion of the clinical phenotyping result has ended. Genetic test results will be revealed and final determination of the diagnosis will be made. The Adjudication Committee will use published diagnostic criteria for specific inherited CM syndromes: Arrhythmogenic cardiomyopathy (AC), Arrhythmogenic Right Ventricular CM (ARVC), Dilated CM (DCM), Hypertrophic CM (HCM), and Left Ventricular Noncompaction CM (LVNC). For AC and DCM, only participants determined to have "definite" AC or DCM according to the diagnostic criteria will be considered as meeting the primary diagnostic endpoint. **Measure:** Number of Participants with Inherited Cardiomyopathy (CM) Syndromes. **Time Frame:** 6 weeks **Description:** The primary diagnostic endpoint will be determined by the Adjudication Committee using the published criteria for Brugada Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Long QT Syndrome (LQTS), Progressive Cardiac Conduction Disease (PCCD), and Short QT Syndrome (SQTS) from the 2013 HRS/EHRA/APHRS Expert Consensus Statement on the Management of Inherited Arrhythmias. **Measure:** Number of Participants with Inherited Arrhythmia Syndromes. **Time Frame:** 6 weeks **Description:** Quantitative imaging and ECG metrics will compare participants who have a pathogenic or likely pathogenic (P/LP) rare variants linked to a CM disease gene compared to controls. Imaging and ECG metrics will be used to assess adverse structural and electrophysiologic changes to the atria and ventricles from inherited cardiomyopathy syndromes. Quantitative metrics will be assessed from contrast-enhanced MRI, signal-averaged ECG, resting 12- lead ECG, Stress treadmill ECG, and ambulatory ECG monitor. Results will be used to test the hypothesis that cases have increased measures of proarrhythmic structural and electrophysiologic changes compared to controls by imaging and ECG endpoints. **Measure:** Number of Participants with Adverse Structural and Electrophysiologic Changes to the Atria and Ventricles for Inherited Cardiomyopathy Syndromes. **Time Frame:** 6 weeks **Description:** Quantitative imaging and ECG metrics will compare participants who have a P/LP rare variants linked to an inherited arrhythmia disease gene and will compare to controls. Imaging and ECG metrics will be used to assess adverse structural and electrophysiologic changes to the atria and ventricles from inherited arrhythmia syndromes. Quantitative metrics will be assessed from resting 12- lead ECG, Stress treadmill ECG, and ambulatory ECG monitor. A procainamide challenge will be used on select participants with a non-diagnostic (type II or III) Brugada pattern identified on their previous resting 12-lead ECG or who are P/LP variant carriers in an identified Brugada susceptibility gene. Results will be used to test the hypothesis that cases have increased measures of proarrhythmic structural and electrophysiologic changes compared to controls by imaging and ECG endpoints. **Measure:** Number of Participants with Adverse Structural and Electrophysiologic Changes to the Atria and Ventricles for Inherited Arrhythmia Syndromes. **Time Frame:** 6 Weeks **Description:** The Adjudication Committee will determine the management recommendations for each participant at the time of case review. The primary analysis will focus on changes in each management category (e.g., medical therapy, physical activity restrictions, stroke prophylaxis, implantable cardioverter-defibrillator utilization) that resulted from discovery of a rare variant, and a secondary analysis will compare the management in each category regardless of whether it was pre-existing or newly initiated. The participant will be contacted, the results will be reviewed by the principal investigator or coinvestigators to discuss the results of the testing. Any recommendations regarding clinical care will be communicated to the participants existing physicians and ensure adequate follow-up is arranged or will assist the participant in establishing care with a qualified physician. **Measure:** Number of Participants with Changes in Management of Inherited Arrhythmia and CM Syndromes. **Time Frame:** 6 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult \> 18 years * Able to provide written informed consent * Previously enrolled in the Vanderbilt Atrial Fibrillation Registry (IVR#020669) * Atrial Fibrillation Ablation Registry (IRB#110881) * Early-onset Atrial Fibrillation Registry (IRB#201666) * Underwent whole genome sequencing/whole exome sequencing or clinical genetic testing and based on those results meets the genetic criteria for cases and controls as defined as a Cardiomyopathy (CM) Rare Variant (P/LP rare variant in CM gene, Arrhythmia Rare Variant (P/LP rare variant in arrhythmia gene), or a Control (no rare variant in CM, arrhythmia, or other Atrial Fibrillation gene). * Diagnosis of Atrial Fibrillation prior to age of 61 (\</=60) Exclusion Criteria: -Pregnant women **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Previous participants who were enrolled in the Vanderbilt Atrial Fibrillation Registry (IVR#020669), Atrial Fibrillation Ablation Registry (IRB#110881), or Early-onset Atrial Fibrillation Registry (IRB#201666). ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** hollie.williams@vumc.org **Name:** Hollie Williams, MSN **Phone:** 615-875-0575 **Role:** CONTACT #### Locations **Location 1:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University Medical Center **State:** Tennessee **Status:** RECRUITING **Zip:** 37232 #### Overall Officials **Official 1:** **Affiliation:** Vanderbilt University Medical Center **Name:** M. B Shoemaker, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Shoemaker MB, Shah RL, Roden DM, Perez MV. How Will Genetics Inform the Clinical Care of Atrial Fibrillation? Circ Res. 2020 Jun 19;127(1):111-127. doi: 10.1161/CIRCRESAHA.120.316365. Epub 2020 Jun 18. **PMID:** 32716712 **Citation:** Yoneda ZT, Anderson KC, Quintana JA, O'Neill MJ, Sims RA, Glazer AM, Shaffer CM, Crawford DM, Stricker T, Ye F, Wells Q, Stevenson LW, Michaud GF, Darbar D, Lubitz SA, Ellinor PT, Roden DM, Shoemaker MB. Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes. JAMA Cardiol. 2021 Dec 1;6(12):1371-1379. doi: 10.1001/jamacardio.2021.3370. **PMID:** 34495297 #### See Also Links **Label:** How Will Genetics Inform the Clinical Care of Atrial Fibrillation? **URL:** https://pubmed.ncbi.nlm.nih.gov/32716712/ **Label:** Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes **URL:** https://pubmed.ncbi.nlm.nih.gov/34495297/ ## Document Section ### Large Document Module #### Large Docs - Date: 2022-07-18 - Filename: ICF_001.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 424925 - Type Abbrev: ICF - Upload Date: 2022-07-20T15:09 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Atrial Fibrillation - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04497779 **Brief Title:** Analysis of Coronavirus Disease 19 (COVID-19) Convalescent Plasma **Official Title:** Evaluation of Coronavirus Disease 19 (COVID-19) Convalescent Plasma #### Organization Study ID Info **ID:** 20204 #### Organization **Class:** OTHER **Full Name:** City of Hope Medical Center #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2020-04000 **Type:** REGISTRY **Domain:** City of Hope Medical Center **ID:** 20204 **Type:** OTHER **ID:** P30CA033572 **Link:** https://reporter.nih.gov/quickSearch/P30CA033572 **Type:** NIH **Domain:** Translational Genomics Research Institute (TGen) **ID:** TGen **Type:** OTHER ### Status Module #### Completion Date **Date:** 2024-06-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-20 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-16 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-06-10 **Type:** ESTIMATED #### Start Date **Date:** 2020-07-13 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2020-08-04 **Type:** ACTUAL **Study First Submit Date:** 2020-06-29 **Study First Submit QC Date:** 2020-07-31 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) **Class:** OTHER **Name:** California Institute for Regenerative Medicine (CIRM) #### Lead Sponsor **Class:** OTHER **Name:** City of Hope Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Plasma from patients who have recovered from coronavirus disease 2019 (COVID-19) is referred to as COVID-19 convalescent plasma (CCP), and may contain antibodies against SARS-CoV-2, the virus responsible for COVID-19. CCP infusion is being evaluated as a therapeutic or prophylactic approach in COVID-19 patients. The goal of this study is to help develop a bank of convalescent plasma in California, especially in medically underserved communities particularly affected by the disease. In parallel, CCP administered to COVID-19 patients will be collected and analyzed to determine whether the antibody profile correlates with clinical outcome. The purpose of this non-therapeutic study is to learn more about the CCP antibody profile and the effect it may have in treating COVID-19 infection. **Detailed Description:** PRIMARY OBJECTIVES: I. Establish a testing service for screening prospective donors of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP). II. Characterize the titer and neutralizing properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in CCP. III. Correlate the SARS-CoV-2 antibody characteristics in CCP with the outcome in severely ill COVID-19 patients treated with CCP. EXPLORATORY OBJECTIVES: I. Facilitate the recruitment of CCP donors in medically underserved areas. II. Develop high-throughput methods for detection/characterization of SARS-CoV-2 neutralizing and non-neutralizing antibodies. III. Develop a bank of convalescent plasma that would be available for future studies relating to the content of CCP. IV. Study the impact of antibody levels, donor characteristics and patient characteristics on outcome in COVID-19 patients treated with CCP. V. Procure blood samples from COVID-19 convalescent volunteers for future COVID-19-related studies. OUTLINE: PROSPECTIVE CCP DONORS: Participants undergo collection of blood and/or nasopharyngeal swabs at the time of screening. Participants' medical records are reviewed. CONVALESCENT BLOOD DONORS WHO CHOOSE NOT TO DONATE CCP: Participants undergo collection of blood sample at the time of screening. Participants' medical records are reviewed. CCP RECIPIENTS: Patients undergo collection collection of blood samples at baseline, between CCP unit infusions, 24 hours after last CCP infusion, and between 14-28 after last CCP infusion. Patients' medical records are reviewed. ### Conditions Module **Conditions:** - Asymptomatic COVID-19 Infection Laboratory-Confirmed - Symptomatic COVID-19 Infection Laboratory-Confirmed ### Design Module #### Bio Spec **Description:** Nasopharyngeal swab, blood samples **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 95 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** PROSPECTIVE CCP DONORS: Participants undergo collection of blood and/or nasopharyngeal swabs at the time of screening. Participants' medical records are reviewed. CONVALESCENT BLOOD DONORS WHO CHOOSE NOT TO DONATE CCP: Participants undergo collection of blood sample at the time of screening. Participants' medical records are reviewed. CCP RECIPIENTS: Patients undergo collection of blood samples at baseline, 12-24 hours after each CCP infusion, and 7 days after last CCP infusion. Patients' medical records are reviewed. **Intervention Names:** - Procedure: Biospecimen Collection - Other: Diagnostic Laboratory Biomarker Analysis - Other: Electronic Health Record Review - Other: Questionnaire Administration **Label:** Screening (biospecimen collection, medical record review, CCP) ### Interventions #### Intervention 1 **Arm Group Labels:** - Screening (biospecimen collection, medical record review, CCP) **Description:** Undergo collection of blood and/or nasopharyngeal swabs **Name:** Biospecimen Collection **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Screening (biospecimen collection, medical record review, CCP) **Description:** Correlative studies **Name:** Diagnostic Laboratory Biomarker Analysis **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Screening (biospecimen collection, medical record review, CCP) **Description:** Donors and recipients have their medical records reviewed. **Name:** Electronic Health Record Review **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Screening (biospecimen collection, medical record review, CCP) **Description:** Ancillary studies **Name:** Questionnaire Administration **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Patient can stay at the hospital for up to 28 days post-CCP infusion **Measure:** Duration of hospitalization (days) **Time Frame:** Up to 28 days post-CCP infusion **Description:** Will be assessed on a 7-point ordinal scale. **Measure:** Time to clinical improvement (days) **Time Frame:** Up to 28 days post-CCP infusion #### Primary Outcomes **Description:** Will be assayed for severe acute respiratory syndrome (SARS-CoV-2) immunoassay, coronavirus (CoV) PepSeq assay, and SARS-CoV-2 lenti-based neutralizing antibody titer. **Measure:** Convalescent plasma (CCP) units infused in coronavirus disease-2019 (COVID-19) patients **Time Frame:** Up to 12 months after enrollment **Description:** Will naturally be compared to reported data from the other studies. Analysis will focus on demonstrating that the antibody content of donor plasma increases the odds of surviving past day 28. Will also develop a nomogram for the probability of success (alive at day 28), accounting for patient, donor material and donor antibody characteristics measurable covariates. **Measure:** All-cause mortality **Time Frame:** At day 28 post-CCP infusion **Description:** Will be examined to see how this relates to the duration of hospitalization. **Measure:** Donor antibody levels **Time Frame:** Up to 28 days post-CCP infusion #### Secondary Outcomes **Description:** Will be assessed on a 7-point ordinal scale, as recommended by the WHO patient outcome R\&D Blueprint Group. **Measure:** Incidence of adverse events **Time Frame:** Up to 28 days post-CCP infusion **Description:** Will be assessed on a 7-point ordinal scale. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or ECMO; 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per protocol RDV administration); 7. Not hospitalized **Measure:** CCP recipient outcomes **Time Frame:** Up to 28 days post-CCP infusion ### Eligibility Module **Eligibility Criteria:** For COVID-19 convalescent individuals: * Age: ≥ 18 years * Evidence of COVID-19 documented by a laboratory test either by: a diagnostic test (e.g., a NP swab) at the time of illness OR a positive serological test for SARS-CoV-2 antibodies after recovery, if prior diagnostic testing was not performed at the time COVID-19 was suspected. Note: If volunteers can't provide evidence of COVID-19, but are otherwise eligible, then we will test them for SARS-CoV-2 antibodies to confirm eligibility. * Be willing to complete a pre-screening questionnaire * Be willing to donate blood samples * Permit medical record review * For prospective CCP donors only: weigh more than 110 pounds and be in general good health For (COVID-19 convalescent plasma (CCP) recipients: * Be enrolled in a clinical trial involving the infusion of CCP for the treatment of COVID-19. * Be willing to provide blood samples * Permit medical record review **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with diagnosis of laboratory-confirmed COVID-19 infection ### Contacts Locations Module #### Locations **Location 1:** **City:** Duarte **Country:** United States **Facility:** City of Hope Medical Center **State:** California **Zip:** 91010 #### Overall Officials **Official 1:** **Affiliation:** City of Hope Medical Center **Name:** John Zaia **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000009784 - Term: Occupational Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC24 - Name: Occupational Diseases ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M10777 - Name: Laboratory Infection - Relevance: HIGH - As Found: Infection Laboratory- - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M12719 - Name: Occupational Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000086382 - Term: COVID-19 - ID: D000007757 - Term: Laboratory Infection ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05626179 **Brief Title:** A Study of [14C]IBI351 in Healthy Subjects **Official Title:** A Mass Balance Study of [14C]IBI351 in Healthy Male Chinese Subjects #### Organization Study ID Info **ID:** CIBI351P002 #### Organization **Class:** INDUSTRY **Full Name:** Innovent Biologics (Suzhou) Co. Ltd. ### Status Module #### Completion Date **Date:** 2023-05-18 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-27 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-03-30 **Type:** ACTUAL #### Start Date **Date:** 2023-02-18 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2022-11-23 **Type:** ACTUAL **Study First Submit Date:** 2022-11-15 **Study First Submit QC Date:** 2022-11-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Innovent Biologics (Suzhou) Co. Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is to evaluate the mass balance of single oral dose of \[14C\] IBI351 in healthy subjects. Six to eight healthy male subjects were planned to be enrolled. After passing the screening, subjects were admitted to hospital and received training on medication, urine and feces collection and other procedures to ensure that they could perform relevant operations according to the protocol and SOP requirements. On the evening before medication, the patient had standard meals, and fasted uniformly overnight. On D1, the suspension containing recommended dose of \[14C\] IBI351 was administered in the morning on an empty stomach. Subjects have standardized meal during the trial and blood, urine, and feces samples were collected and safety laboratory tests were performed as scheduled. ### Conditions Module **Conditions:** - Healthy Subjects ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 6 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Recommended dose of \[14C\] IBI351 **Intervention Names:** - Drug: [14C] IBI351 **Label:** [14C] IBI351 **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - [14C] IBI351 **Description:** The oral formulation of \[14C\] IBI351 was formulated as a suspension for subjects to take orally in drinking water under fasting conditions **Name:** [14C] IBI351 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** cumulative recovery of total radioactivity in excreta (urine and feces) **Time Frame:** approximately 30 days after first dose **Measure:** percentage of metabolite in total exposure AUC in plasma (% AUC) **Time Frame:** approximately 30 days after first dose **Measure:** percentage of each metabolite in urine to administered dose (% of administered dose) **Time Frame:** approximately 30 days after first dose **Measure:** Percentage of each metabolite in feces to administered dose (% of administered dose) **Time Frame:** approximately 30 days after first dose **Measure:** total radioactivity ratio for whole blood/plasma **Time Frame:** approximately 30 days after first dose **Measure:** maximum concentrations (Cmax ) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose **Measure:** time-to-maximum concentration (Tmax) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose **Measure:** half-life (t1/2) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose **Measure:** area under the curve from time 0 to the last time point (AUC0-t) for total plasma radioactivityarea under the curve from time 0 to the last time point (AUC0-t) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose **Measure:** area under the curve from time 0 to infinity(AUC0-inf) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose **Measure:** apparent clearance (CL/F) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose **Measure:** apparent volume of distribution(Vz/F) for total plasma radioactivity **Time Frame:** approximately 30 days after first dose #### Secondary Outcomes **Measure:** maximum concentrations (Cmax ) for plasma **Time Frame:** approximately 30 days after first dose **Measure:** time-to-maximum concentration (Tmax) for plasma **Time Frame:** approximately 30 days after first dose **Measure:** area under the curve from time 0 to the last time point (AUC0-t) for plasma **Time Frame:** approximately 30 days after first dose **Measure:** area under the curve from time 0 to infinity(AUC0-inf) for plasma **Time Frame:** approximately 30 days after first dose **Measure:** apparent clearance (CL/F) for plasma **Time Frame:** approximately 30 days after first dose **Measure:** apparent volume of distribution(Vz/F) for plasma **Time Frame:** approximately 30 days after first dose **Measure:** adverse events **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in vital signs **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in ECG parameters **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in physical examination **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in hematology parameters **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in clinical chemistry parameters **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in routine urinalysis parameters **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in routine stool parameters **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in coagulation parameters **Time Frame:** approximately 30 days after first dose **Measure:** abnormality in Troponin T (TnT) **Time Frame:** approximately 30 days after first dose ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria： 1. Voluntarily sign the informed consent form before the trial, and fully understand the content, process and possible adverse reactions of the trial. 2. Healthy male subjects aged 18 to 45 years (including both ends) at the time of signing informed consent. 3. Body weight is not less than 50 kg, and body mass index (BMI) is in the range of 19 \~ 26 kg/m2 (including both ends). 4. Vital signs, physical examination, laboratory tests (including blood routine, urine routine, blood biochemistry, coagulation, etc.), chest radiography, 12-lead ECG and other results were unremarkable; or abnormal examination results but judged by the investigator as clinically insignificant. Exclusion Criteria 1. allergic constitution; known hypersensitivity to any component of the test drug or its preparation. 2. have special requirements for diet and cannot abide by the unified diet; or lactose intolerance. 3. history of dysphagia or any gastrointestinal disease that affects drug absorption. 4. blood donation or massive blood loss (\> 200 mL) within 3 months before screening, or blood transfusion within 1 month. 5. Have taken an investigational product or participated in any clinical trial within 3 months before taking the study drug. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Nanjing **Country:** China **Facility:** The First Affiliated Hospital of Nanjing Medical University **State:** Jiangsu **Zip:** 210029 ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04766879 **Acronym:** AEGIS Kenya **Brief Title:** Spatial Repellents for the Prevention of Malaria in Kenya **Official Title:** A Cluster Randomized Trial of the Efficacy of a Spatial Repellent (the Envelope) on Plasmodium Falciparum Malaria Incidence as Measured by Time to First Infection in Western Kenya #### Organization Study ID Info **ID:** 19-08-5506 #### Organization **Class:** OTHER **Full Name:** University of Notre Dame ### Status Module #### Completion Date **Date:** 2023-12-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-15 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-10-23 **Type:** ACTUAL #### Start Date **Date:** 2021-03-02 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2021-02-23 **Type:** ACTUAL **Study First Submit Date:** 2021-02-08 **Study First Submit QC Date:** 2021-02-19 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** SC Johnson, A Family Company **Class:** OTHER **Name:** Kenya Medical Research Institute **Class:** FED **Name:** Centers for Disease Control and Prevention **Class:** UNKNOWN **Name:** fhiClinical #### Lead Sponsor **Class:** OTHER **Name:** University of Notre Dame #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Spatial repellents are chemical-based devices that when placed in a room, make that room non-conducive for mosquitoes. These tools can be used to help in the fight against vector borne diseases such as malaria and dengue. However, their efficacy in reducing mosquito biting and therefore malaria transmission has never been evaluated in Africa. This study will evaluate the efficacy of a spatial repellent in reducing mosquito biting on human beings and measure the impact any reduced biting will have on malaria transmission. The investigators will recruit and follow-up 5,984 children between 6 months and \<10 years of age in Busia County to determine how many times they will be infected with malaria in villages where the investigators will have distributed spatial repellents and compare the rate of infection to villages where the investigators will not have distributed the repellent devices. Additionally, the investigators will measure whether the distribution of spatial repellents in one village will drive mosquitoes to their neighboring houses thereby increasing malaria transmission in those areas. The children participating in the study will be divided into 3 groups (cohorts). The first group will be followed up during the first 4 months before any intervention is distributed and the purpose here will be to determine that the villages are comparable. After this, the investigators will recruit the next group of participants and follow them up for 1 year and repeat this again for another year. During the follow-up, the children will be asked to come to the health facility where they will be tested for malaria using RDT or blood slide for microscopy. Every two weeks, a member of the study team will come to the participant's house and ask them if they had any history of fever. If the participants had fever, they will be tested for malaria. All children who turn out to be positive for malaria by RDT will be treated free of charge. At the same time, the investigators shall also perform mosquito collections to determine the impact of spatial repellents on the density of Anopheles mosquitoes. **Detailed Description:** Spatial repellents (SRs) have been widely used for the prevention of mosquito bites but their protective efficacy (PE) in reducing mosquito-borne diseases has never been evaluated in Africa. To address this knowledge gap, western Kenya was selected as a site to estimate the impact of a transfluthrin-based spatial repellent on malaria-related outcomes in Busia County, where baseline malaria transmission ranges from 2.5 to 4.1 new infections per person per year. A total of 5,984 children between 6 months and \<10 years of age will be enrolled in three separate cohorts (baseline, cohort 1 and cohort 2). A total of 2,040 children from among 60 clusters will be enrolled for a four-month baseline prior to placement of the SR intervention. After baseline, a total of 1,972 participants from among 58 clusters, will be enrolled into cohort 1 and followed for one year. Cohort 2, consisting of a total of 1,972 children, will be enrolled from among 58 clusters to provide a total of two years of follow up. Children who have been selected for inclusion in the baseline cohort will be eligible for selection to cohort 1 or 2 but not both. Cohort 1 and Cohort 2 during intervention will be split into two groups, one to estimate the direct effect of the SR (total of 1,624 children, 812 per follow up year) and a second to estimate the degree of diversion (or mass effect) of mosquitoes and malaria transmission from persons protected by the SR to persons who are unprotected (total of 2,320 children, 1,160 per follow up year). All cohorts will be followed once every two weeks with finger prick blood samples taken once every 4 weeks to test for malaria or whenever a participant reports a recent (within 48 hours) history of fever. The incidence of malaria in the baseline cohort will be used to validate underlying assumptions prior to intervention. The incidence of malaria in each cohort followed with intervention will be estimated and compared to determine the benefit of using an SR in an area with high, year-round transmission of malaria. Monthly collections of mosquitoes using CDC light traps will be conducted to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. Quarterly human landing catches will be done to assess the behavioral effects of the SR. The primary hypothesis on PE against the first-time malaria infection will be estimated by comparing the hazard rates of first-time malaria infection between SR and placebo upon the completion of the study in the ITT population. ### Conditions Module **Conditions:** - Malaria **Keywords:** - Malaria - Spatial Repellent - Transfluthrin - Vector-borne diseases - Mosquito vectors - Incidence ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 5984 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Transfluthrin **Intervention Names:** - Device: Transfluthrin **Label:** Spatial Repellent **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Inert ingredients **Intervention Names:** - Device: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Spatial Repellent **Description:** Passive emanator with formulated transfluthrin **Name:** Transfluthrin **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Passive emanator with formulated inert ingredients **Name:** Placebo **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** First-time malaria infection in core zones during intervention period. **Time Frame:** 12 months #### Secondary Outcomes **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** Overall new malaria infections in core zones during intervention period. **Time Frame:** 12 months **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** Overall new malaria infections in buffer zones during intervention period. **Time Frame:** 12 months **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** Parasite-species-specific first-time malaria infections in the core zones. **Time Frame:** 12 months **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** Parasite-species-specific overall malaria infections in the core zones. **Time Frame:** 12 months **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** The first-time malaria infections in buffer zones during intervention period. **Time Frame:** 12 months **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** The first time malaria infections by two age groups (≤ 59 months old; 5 years to 10 years old). **Time Frame:** 12 months **Description:** Measured by microscopy in children aged between 6 months to 10 years. **Measure:** Overall malaria infections by two age groups (≤ 59 months old; 5 years to 10 years old). **Time Frame:** 12 months **Description:** Measured by human-landing catch (HLC) during 12-h intervals on a quarterly basis during intervention period. **Measure:** Anopheline-human contact (indoor and outdoor) using human biting rate (HBR) as an indicator for all anophelines and by anopheline species. **Time Frame:** 12 months **Description:** Measured by mosquito ovarian dissections from a sub-sample of anophelines collected during HLC procedures during intervention period. **Measure:** Anopheline parity rate as an indicator of population age structure for all anophelines and by anopheline species. **Time Frame:** 12 months **Description:** Measured by laboratory detection of sporozoites in mosquito head-preps from a sub-sample of anophelines collected during HLC and/or CDC-light trap procedures during intervention period. **Measure:** Anopheline infectivity using sporozoite rate as an indicator for all anophelines and by anopheline species. **Time Frame:** 12 months **Description:** Measured by calculating the number of sporozoite-infected anopheline mosquitoes captured per person during intervention period from HLC and/or CDC-light trap procedures. **Measure:** Anopheline infectivity using EIR as an indicator for all anophelines and by anopheline species. **Time Frame:** 12 months **Description:** Measured by CDC-light trap collections during 12-h intervals on a monthly basis during intervention period. **Measure:** CDC-light trap indoor density for all anophelines and by anopheline species. **Time Frame:** 12 months **Description:** Measured by WHO filter paper test and CDC bottle assays during baseline and intervention period. **Measure:** Insecticide resistance. **Time Frame:** 28 months **Description:** Measured by solicited and unsolicited reports during baseline and intervention period. Mean, minimum and maximum frequency and percentage of AEs and SAEs across clusters among enrolled subjects will be summarized by treatment arm. **Measure:** Adverse Events and Serious Adverse Events. **Time Frame:** 28 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Children aged 6 months to \<10 years * Hb \> 5mg/dl * Sleeps in cluster \>90% of nights during any given month * No plans for extended travel (\>1month) outside of home during study * Not participating in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure during the Trial * Provision of informed consent form signed by the parent(s) or guardian * Children not on regular malaria prophylaxis° such as Proguanil * Willingness to take AL and no history of hypersensitivity to AL Exclusion Criteria: * Children \< 6 months or ≥ 10 years * Hb ≤ 5 mg/dL, or Hb \< 6mg/dL with signs of clinical decompensation * Sleeps in cluster \<90% of nights during any given month * Plans for extended travel (\>1month) outside of home during study * Participating or planned participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure during the trial * No provision of informed consent form signed by the parent(s) or guardian * Children on regular malaria prophylaxis° such as Proguanil * Unwillingness or refusal to take AL and history of AL hypersensitivity * Other malaria prophylaxis medicines: Mefloquine, Atavaquone/Proguanil (Malarone), Doxycycline, Tafenoquine, Sulfadoxine-Pyrimethamine (Fansidar), Amodiaquine and Co-trimoxazole (Septrin) **Healthy Volunteers:** True **Maximum Age:** 10 Years **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Busia **Country:** Kenya **Facility:** Centers for Disease Control and Prevention **State:** Busia County **Location 2:** **City:** Busia **Country:** Kenya **Facility:** Kenya Medical Research Institute (KEMRI) **State:** Busia County #### Overall Officials **Official 1:** **Affiliation:** University of Notre Dame **Name:** John P Grieco, Ph.D. **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Kenya Medical Research Institute **Name:** Eric Ochomo, Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Open-access repository distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Description:** Analytical data will be anonymized and GPS tag-blurred to remove sensitive information prior to sharing. **Info Types:** - STUDY_PROTOCOL - SAP - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** The data and supporting information will be made available 12 months following completion of data analysis and will remain open access in the public domain. ### References Module #### References **Citation:** Hamel MJ, Adazu K, Obor D, Sewe M, Vulule J, Williamson JM, Slutsker L, Feikin DR, Laserson KF. A reversal in reductions of child mortality in western Kenya, 2003-2009. Am J Trop Med Hyg. 2011 Oct;85(4):597-605. doi: 10.4269/ajtmh.2011.10-0678. **PMID:** 21976557 **Citation:** Zhou G, Afrane YA, Vardo-Zalik AM, Atieli H, Zhong D, Wamae P, Himeidan YE, Minakawa N, Githeko AK, Yan G. Changing patterns of malaria epidemiology between 2002 and 2010 in Western Kenya: the fall and rise of malaria. PLoS One. 2011;6(5):e20318. doi: 10.1371/journal.pone.0020318. Epub 2011 May 23. **PMID:** 21629783 **Citation:** Ogoma SB, Moore SJ, Maia MF. A systematic review of mosquito coils and passive emanators: defining recommendations for spatial repellency testing methodologies. Parasit Vectors. 2012 Dec 7;5:287. doi: 10.1186/1756-3305-5-287. **PMID:** 23216844 **Citation:** Ogoma SB, Ngonyani H, Simfukwe ET, Mseka A, Moore J, Killeen GF. Spatial repellency of transfluthrin-treated hessian strips against laboratory-reared Anopheles arabiensis mosquitoes in a semi-field tunnel cage. Parasit Vectors. 2012 Mar 20;5:54. doi: 10.1186/1756-3305-5-54. **PMID:** 22433128 **Citation:** Ogoma SB, Ngonyani H, Simfukwe ET, Mseka A, Moore J, Maia MF, Moore SJ, Lorenz LM. The mode of action of spatial repellents and their impact on vectorial capacity of Anopheles gambiae sensu stricto. PLoS One. 2014 Dec 8;9(12):e110433. doi: 10.1371/journal.pone.0110433. eCollection 2014. **PMID:** 25485850 **Citation:** Achee NL, Bangs MJ, Farlow R, Killeen GF, Lindsay S, Logan JG, Moore SJ, Rowland M, Sweeney K, Torr SJ, Zwiebel LJ, Grieco JP. Spatial repellents: from discovery and development to evidence-based validation. Malar J. 2012 May 14;11:164. doi: 10.1186/1475-2875-11-164. **PMID:** 22583679 **Citation:** Lucas JR, Shono Y, Iwasaki T, Ishiwatari T, Spero N, Benzon G. U.S. laboratory and field trials of metofluthrin (SumiOne) emanators for reducing mosquito biting outdoors. J Am Mosq Control Assoc. 2007 Mar;23(1):47-54. doi: 10.2987/8756-971X(2007)23[47:ULAFTO]2.0.CO;2. **PMID:** 17536367 **Citation:** Kawada H, Temu EA, Minjas JN, Matsumoto O, Iwasaki T, Takagi M. Field evaluation of spatial repellency of metofluthrin-impregnated plastic strips against Anopheles gambiae complex in Bagamoyo, coastal Tanzania. J Am Mosq Control Assoc. 2008 Sep;24(3):404-9. doi: 10.2987/5743.1. **PMID:** 18939693 **Citation:** Syafruddin D, Bangs MJ, Sidik D, Elyazar I, Asih PB, Chan K, Nurleila S, Nixon C, Hendarto J, Wahid I, Ishak H, Bogh C, Grieco JP, Achee NL, Baird JK. Impact of a spatial repellent on malaria incidence in two villages in Sumba, Indonesia. Am J Trop Med Hyg. 2014 Dec;91(6):1079-87. doi: 10.4269/ajtmh.13-0735. Epub 2014 Oct 13. **PMID:** 25311699 **Citation:** Hill N, Zhou HN, Wang P, Guo X, Carneiro I, Moore SJ. A household randomized, controlled trial of the efficacy of 0.03% transfluthrin coils alone and in combination with long-lasting insecticidal nets on the incidence of Plasmodium falciparum and Plasmodium vivax malaria in Western Yunnan Province, China. Malar J. 2014 May 31;13:208. doi: 10.1186/1475-2875-13-208. **PMID:** 24885993 **Citation:** Ochomo EO, Gimnig JE, Bhattarai A, Samuels AM, Kariuki S, Okello G, Abong'o B, Ouma EA, Kosgei J, Munga S, Njagi K, Odongo W, Liu F, Grieco JP, Achee NL. Evaluation of the protective efficacy of a spatial repellent to reduce malaria incidence in children in western Kenya compared to placebo: study protocol for a cluster-randomized double-blinded control trial (the AEGIS program). Trials. 2022 Apr 5;23(1):260. doi: 10.1186/s13063-022-06196-x. **PMID:** 35382858 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011528 - Term: Protozoan Infections - ID: D000010272 - Term: Parasitic Diseases - ID: D000007239 - Term: Infections - ID: D000096724 - Term: Mosquito-Borne Diseases - ID: D000079426 - Term: Vector Borne Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M11280 - Name: Malaria - Relevance: HIGH - As Found: Malaria - ID: M19133 - Name: Malaria, Falciparum - Relevance: LOW - As Found: Unknown - ID: M2054 - Name: Vector Borne Diseases - Relevance: LOW - As Found: Unknown - ID: M14388 - Name: Protozoan Infections - Relevance: LOW - As Found: Unknown - ID: M13185 - Name: Parasitic Diseases - Relevance: LOW - As Found: Unknown - ID: M3255 - Name: Mosquito-Borne Diseases - Relevance: LOW - As Found: Unknown - ID: T3571 - Name: Malaria - Relevance: HIGH - As Found: Malaria ### Condition Browse Module - Meshes - ID: D000008288 - Term: Malaria ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03780179 **Brief Title:** MMR at 6 Months Trial **Official Title:** Measles-mumps-rubella Vaccine at 6 Months of Age, Immunology, and Childhood Morbidity in a High-income Setting #### Organization Study ID Info **ID:** LGS.MMR.01.2016.2022 #### Organization **Class:** OTHER **Full Name:** Rigshospitalet, Denmark ### Status Module #### Completion Date **Date:** 2022-01-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-01-13 **Type:** ACTUAL **Last Update Submit Date:** 2022-01-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-01-07 **Type:** ACTUAL #### Start Date **Date:** 2019-04-15 **Type:** ACTUAL **Status Verified Date:** 2022-01 #### Study First Post Date **Date:** 2018-12-19 **Type:** ACTUAL **Study First Submit Date:** 2018-12-17 **Study First Submit QC Date:** 2018-12-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Rigshospitalet, Denmark #### Responsible Party **Investigator Affiliation:** Rigshospitalet, Denmark **Investigator Full Name:** Lone Graff Stensballe **Investigator Title:** Pediatrician, associate professor, PhD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Randomised, double-blind clinical trial to test humoral and cellular immunogenicity, and potential in-direct beneficial effect of the MMRvaxpro-vaccine administered at 6 months of age ### Conditions Module **Conditions:** - Meales-mumps-rubella Vaccine **Keywords:** - measles-mumps-rubella vaccine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomization to intervention: MMRvaxpro at 6 months of age, or placebo-vaccine (solvent only) ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 6540 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: MMRvaxpro **Label:** MMRvaxpro **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Biological: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - MMRvaxpro **Description:** MMRvaxpro vaccine **Name:** MMRvaxpro **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo **Name:** Placebo **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** The plaque reduction neutralisation test (PRNT), which measures the serum dilution capable of preventing 50% of plaque formation induced by measles virus in cell cultures, has been considered the most reliable criterion for the serologic evaluation of measles immunity. For PNRT, the protective cutoff titer is defined to be \>120. A frequency of 95% seroconversion rate, i.e. children mounting a protective level of humoral immunity according to the abovementioned cutoff value after MMR-vaccination at 6 M of age will be considered sufficient to suggest implementation of MMR at 6 M in the Danish vaccination programme. **Measure:** Humoral immunogenicity **Time Frame:** 1 months after intervention **Description:** Significant decrease in hospitalisation for infection measured as repeated events from 6 to 12 months of age in children randomised to MMR at 6 M compared to children randomised to placebo. Information about hospitalisation for infection will be obtained from the national Danish Patient Register, where all Danish inhabitants are followed-up during all hospital contacts. **Measure:** Hospitalisation for infection **Time Frame:** 6-12 months of age ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Gestational age of 32+ weeks. * Birth weight of 1000+ grams. * Signed informed consent from the parents. Exclusion Criteria: * Immune-deficiency (primary or acquired) or -suppression. * Intake of immune modulating medicine (including high doses of corticosteroids) (M-M-RVAXPRO is not contraindicated in individuals who are receiving topical or low-dose parenteral corticosteroids, e.g. for asthma prophylaxis or replacement therapy). * Signs of severe illness or major malformation. * No Danish-speaking parent. * Children with a history of anaphylactic, anaphylactoid, or other immediate reactions (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) subsequent to egg ingestion are excluded. * Children with known fructose intolerance, thrombocytopenia or any coagulation disorder will be excluded. * Children who received blood or plasma transfusions, or administration of human immune serum globulin within the last 3 months will be excluded. * Further, children are excluded from the trial if any contraindication is suspected: history of hypersensitivity to any measles, mumps, or rubella vaccine, or to any of the excipients, including neomycin. * Children with active untreated tuberculosis, blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic systems will be excluded. **Maximum Age:** 7 Months **Minimum Age:** 5 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Copenhagen **Country:** Denmark **Facility:** Rigshospitalet **State:** Copenhagen Ø **Zip:** 2100 **Location 2:** **City:** Herlev **Country:** Denmark **Facility:** Herlev Hospital **Zip:** 2730 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000018355 - Term: Rubivirus Infections - ID: D000014036 - Term: Togaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11440 - Name: Measles - Relevance: LOW - As Found: Unknown - ID: M15229 - Name: Rubella - Relevance: HIGH - As Found: Rubella - ID: M12064 - Name: Mumps - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M16792 - Name: Togaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: T3653 - Name: Measles - Relevance: LOW - As Found: Unknown - ID: T5072 - Name: Rubella - Relevance: HIGH - As Found: Rubella ### Condition Browse Module - Meshes - ID: D000012409 - Term: Rubella ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01951079 **Brief Title:** Intra Amniotic Injection of DIGOXIN for Feticide in Second Trimester Termination of Pregnancy **Official Title:** The Safety and Outcome of Intra-amniotic DIGOXIN Injection for Feticide Prior to Second Trimester Abortion #### Organization Study ID Info **ID:** MMC130077-12CTIL #### Organization **Class:** OTHER **Full Name:** Meir Medical Center ### Status Module #### Completion Date **Date:** 2014-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2013-09-26 **Type:** ESTIMATED **Last Update Submit Date:** 2013-09-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2014-11 **Type:** ESTIMATED #### Start Date **Date:** 2013-11 **Status Verified Date:** 2013-07 #### Study First Post Date **Date:** 2013-09-26 **Type:** ESTIMATED **Study First Submit Date:** 2013-07-16 **Study First Submit QC Date:** 2013-09-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Meir Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** In second trimester abortion above 22 weeks the investigators usually inject intra-cardiac Kcl for feticide. Digoxin intra-amniotic injection has been described in the literature in doses of 1-1.5 mg. with a success rate of about 80%, and up to 24 weeks. Our aim in this study is to investigate the safety and success rate of 1.5-2 mg. digoxin, intra-amniotic up to 30 weeks pregnancy . **Detailed Description:** * The digoxin will be injected intra-amniotic with U.S guided, trying to avoid any placental passage or intravascular injection / * Any patient will have prior to the procedure a full examination including E.C.G and cardiac clearance. ### Conditions Module **Conditions:** - Arrhythmia - ECG Changes - Hypotension **Keywords:** - Digoxin - Intra-amniotic injection - feticide - second trimester abortion ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** all patients admitting to second trimester abortion above 22 weeks will be injected intra-amniotic DIGOXIN for feticide . **Intervention Names:** - Drug: Intra-amniotic injection of DIGOXIN **Label:** second trimester abortion , feticide **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - second trimester abortion , feticide **Name:** Intra-amniotic injection of DIGOXIN **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** To measure the Success rate of intra-amniotic Digoxin injection for feticide prior to second trimester abortion **Measure:** Efficiency of intra-amniotic Digoxin injection for second trimester feticide **Time Frame:** a year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * healthy women with no medical, cardiac, hypertension, liver or renal problems - pregnant in their 20-30 week gestation, * that need to have abortion due to fetal anomalies or any other reason * need to have feticide prior to the procedure Exclusion Criteria: * any patient with medical problem that may be a contra-indication to Digoxin * cardiac problems, * prior cardiac surgery, * liver or kidney disease, * hyper tension etc. **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** kleinz@clalit.org.il **Name:** Zvi Klein, M.D **Phone:** 972-9-7472544 **Role:** CONTACT **Contact 2:** **Name:** Regina agizim, M.D. **Phone:** 972-9-7472561 **Role:** CONTACT #### Locations **Location 1:** **City:** Kefar-saba **Country:** Israel **Facility:** Dr. Zvi Klein **Location 2:** **City:** Kefar-saba **Country:** Israel **Facility:** Sapir medical center ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10072 - Name: Hypotension - Relevance: HIGH - As Found: Hypotension - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007022 - Term: Hypotension ### Intervention Browse Module - Ancestors - ID: D000000889 - Term: Anti-Arrhythmia Agents - ID: D000002316 - Term: Cardiotonic Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: CaAg - Name: Cardiotonic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M7265 - Name: Digoxin - Relevance: HIGH - As Found: Plexus - ID: M4213 - Name: Anti-Arrhythmia Agents - Relevance: LOW - As Found: Unknown - ID: M5572 - Name: Cardiotonic Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000004077 - Term: Digoxin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00396279 **Brief Title:** Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone **Official Title:** An Open-Label, Multi-Center, Phase 2 Safety and Efficacy Study of Denosumab (AMG 162) in Subjects With Recurrent or Unresectable Giant Cell Tumor (GCT) of Bone #### Organization Study ID Info **ID:** 20040215 #### Organization **Class:** INDUSTRY **Full Name:** Amgen ### Status Module #### Completion Date **Date:** 2011-02-01 **Type:** ACTUAL #### Disp First Post Date **Date:** 2010-06-14 **Type:** ESTIMATED **Disp First Submit Date:** 2010-06-10 **Disp First Submit QC Date:** 2010-06-10 #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-04-07 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-03-05 **Type:** ESTIMATED **Results First Submit Date:** 2014-01-23 **Results First Submit QC Date:** 2014-01-23 #### Start Date **Date:** 2006-07-10 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2006-11-06 **Type:** ESTIMATED **Study First Submit Date:** 2006-11-02 **Study First Submit QC Date:** 2006-11-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Amgen #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone. ### Conditions Module **Conditions:** - GCT - Giant Cell Tumor of Bone **Keywords:** - Giant Cell Tumor of Bone ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 37 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **Intervention Names:** - Biological: Denosumab - Dietary Supplement: Calcium/Vitamin D **Label:** Denosumab **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Denosumab **Description:** Administered by subcutaneous injection **Name:** Denosumab **Other Names:** - Xgeva® **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Denosumab **Name:** Calcium/Vitamin D **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent \< 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis. **Measure:** Percentage of Participants With Giant Cell Tumor Response **Time Frame:** From enrollment until 25 weeks #### Secondary Outcomes **Description:** Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time. **Measure:** Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine **Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 **Description:** Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time. **Measure:** Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen) **Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 **Description:** Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA). **Measure:** Serum Denosumab Trough Concentrations **Time Frame:** Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49. **Description:** An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug. **Measure:** Number of Participants With Adverse Events (AEs) **Time Frame:** From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months **Description:** Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study. **Measure:** Number of Participants With Anti-Denosumab Antibodies **Time Frame:** From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults, 18 years and older * Histologically confirmed and measurable giant cell tumor (GCT) * Recurrent GCT confirmed by radiology or unresectable GCT * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: * Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab * Radiation to affected region within 28 days before enrollment to study * Known diagnosis of osteosarcoma or brown tumor of bone * Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ * Concurrent treatment with bisphosphonates, calcitonin, or interferon. Other criteria also apply. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Amgen **Name:** MD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18. **PMID:** 22711702 **Citation:** Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10. **PMID:** 20149736 **Citation:** Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018 Sep 19;16(1):191. doi: 10.1186/s12957-018-1478-3. **PMID:** 30231890 #### See Also Links **Label:** AmgenTrials clinical trials website **URL:** http://www.amgentrials.com ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000009372 - Term: Neoplasms, Connective Tissue - ID: D000018204 - Term: Neoplasms, Connective and Soft Tissue - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009371 - Term: Neoplasms by Site - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000018213 - Term: Neoplasms, Bone Tissue ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M5138 - Name: Bone Neoplasms - Relevance: HIGH - As Found: Tumor of Bone - ID: M8982 - Name: Giant Cell Tumors - Relevance: HIGH - As Found: Giant Cell Tumor - ID: M20358 - Name: Giant Cell Tumor of Bone - Relevance: HIGH - As Found: Giant Cell Tumor of Bone - ID: M12317 - Name: Neoplasms, Connective Tissue - Relevance: LOW - As Found: Unknown - ID: M20350 - Name: Neoplasms, Connective and Soft Tissue - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M20359 - Name: Neoplasms, Bone Tissue - Relevance: LOW - As Found: Unknown - ID: T2489 - Name: Giant Cell Tumor of Bone - Relevance: HIGH - As Found: Giant Cell Tumor of Bone ### Condition Browse Module - Meshes - ID: D000005870 - Term: Giant Cell Tumors - ID: D000001859 - Term: Bone Neoplasms - ID: D000018212 - Term: Giant Cell Tumor of Bone ### Intervention Browse Module - Ancestors - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000077264 - Term: Calcium-Regulating Hormones and Agents - ID: D000050071 - Term: Bone Density Conservation Agents ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: HIGH - As Found: Ultrasound - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: HIGH - As Found: Radiation - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M417 - Name: Denosumab - Relevance: HIGH - As Found: 0.05 - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: T442 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: T479 - Name: Vitamin D3 - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014807 - Term: Vitamin D - ID: D000069448 - Term: Denosumab - ID: D000002118 - Term: Calcium ### Misc Info Module #### Removed Countries - Country: Australia - Country: France - Country: United States - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency. #### Event Groups **Group ID:** EG000 **Title:** Denosumab 120 mg Q4W **Description:** Participants received a dose loading regimen of 3 subcutaneous injections of denosumab 120 mg every week for 3 weeks (study Days 1, 8, and 15), followed by a week of rest, and then 120 mg denosumab once every 4 weeks (Q4W) from Day 29. **ID:** EG000 **Other Num Affected:** 25 **Other Num at Risk:** 37 **Serious Number Affected:** 5 **Serious Number At Risk:** 37 **Title:** Denosumab 120 mg Q4W **Frequency Threshold:** 5 #### Other Events **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Asthenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 11.0 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 11.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 11.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 11.0 **Term:** Anorexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Hypocalcaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Hypophosphataemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Muscle spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Musculoskeletal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 11.0 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 11.0 #### Serious Events **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Lower respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Ankle fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Metastases to lung **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Acute respiratory distress syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 11.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 37 **Time Frame:** up to 1 year 6 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 37 **Units:** Participants ### Group **ID:** BG000 **Title:** Denosumab **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.3 **Value:** 33.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 17 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 27 **Class Title:** White or Caucasian #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 5 **Class Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 3 **Class Title:** Asian ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Class Title:** Primary unresectable #### Measurement **Group ID:** BG000 **Value:** 18 **Class Title:** Recurrent unresectable #### Measurement **Group ID:** BG000 **Value:** 6 **Class Title:** Recurrent resectable ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Class Title:** 0 - Fully Active #### Measurement **Group ID:** BG000 **Value:** 21 **Class Title:** 1 - Restricted but ambulatory #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** 2 - Ambulatory but unable to work #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** 3 - Limited selfcare, confined to bed >50% daytime #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** 4 - Completely disabled #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** Missing ### Measure #### Measurement **Group ID:** BG000 **Spread:** 16.1 **Value:** 28.7 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 **Class Title:** Lower extremities #### Measurement **Group ID:** BG000 **Value:** 5 **Class Title:** Upper extremities #### Measurement **Group ID:** BG000 **Value:** 9 **Class Title:** Pelvis #### Measurement **Group ID:** BG000 **Value:** 3 **Class Title:** Spine #### Measurement **Group ID:** BG000 **Value:** 9 **Class Title:** Pulmonary disease #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Dorsal vertebrae #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Pelvic region #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Missing **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Giant Cell Tumor Disease Type **Unit of Measure:** participants ### Measure 5 **Description:** 0: Fully active, able to carry on all pre-disease performance without restriction; 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2. Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3. Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4. Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. **Parameter Type:** NUMBER **Title:** Eastern Cooperative Oncology Group (ECOG) Performance Status **Unit of Measure:** participants ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Percent of giant cells in tumor on pre-treatment biopsy **Unit of Measure:** percentage of giant cells in tumor ### Measure 7 **Parameter Type:** NUMBER **Title:** Location of target lesion **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Organization:** Amgen Inc. **Phone:** 866-572-6436 **Title:** Study Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 69.7 - **Spread:** - **Upper Limit:** 95.2 - **Value:** 85.7 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -79.6 - **Spread:** - **Upper Limit:** -15.0 - **Value:** -70.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -85.7 - **Spread:** - **Upper Limit:** -42.9 - **Value:** -77.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -84.2 - **Spread:** - **Upper Limit:** -36.0 - **Value:** -60.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -79.3 - **Spread:** - **Upper Limit:** -37.1 - **Value:** -59.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -80.1 - **Spread:** - **Upper Limit:** -19.1 - **Value:** -64.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -76.2 - **Spread:** - **Upper Limit:** 3.6 - **Value:** -56.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -78.4 - **Spread:** - **Upper Limit:** -22.8 - **Value:** -52.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -83.8 - **Spread:** - **Upper Limit:** 22.0 - **Value:** -35.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -83.4 - **Spread:** - **Upper Limit:** -41.4 - **Value:** -71.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -78.1 - **Spread:** - **Upper Limit:** -22.4 - **Value:** -57.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -81.8 - **Spread:** - **Upper Limit:** -47.5 - **Value:** -59.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -74.0 - **Spread:** - **Upper Limit:** -0.9 - **Value:** -59.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -81.5 - **Spread:** - **Upper Limit:** -29.3 - **Value:** -49.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -78.4 - **Spread:** - **Upper Limit:** -21.9 - **Value:** -65.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -92.5 - **Spread:** - **Upper Limit:** 23.1 - **Value:** -59.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -79.6 - **Spread:** - **Upper Limit:** 33.2 - **Value:** -69.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -88.8 - **Spread:** - **Upper Limit:** -13.4 - **Value:** -64.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -47.5 - **Spread:** - **Upper Limit:** -47.5 - **Value:** -47.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -86.8 - **Spread:** - **Upper Limit:** -66.7 - **Value:** -76.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -53.8 - **Spread:** - **Upper Limit:** 27.1 - **Value:** -13.3 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -85.2 - **Spread:** - **Upper Limit:** -71.2 - **Value:** -78.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -87.9 - **Spread:** - **Upper Limit:** -66.1 - **Value:** -79.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -85.7 - **Spread:** - **Upper Limit:** -71.3 - **Value:** -80.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -85.2 - **Spread:** - **Upper Limit:** -70.4 - **Value:** -82.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -87.0 - **Spread:** - **Upper Limit:** -66.4 - **Value:** -82.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -86.5 - **Spread:** - **Upper Limit:** -69.2 - **Value:** -79.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -85.2 - **Spread:** - **Upper Limit:** -60.3 - **Value:** -82.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -83.2 - **Spread:** - **Upper Limit:** -59.0 - **Value:** -74.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -87.0 - **Spread:** - **Upper Limit:** -69.6 - **Value:** -82.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -89.6 - **Spread:** - **Upper Limit:** -58.5 - **Value:** -86.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -86.4 - **Spread:** - **Upper Limit:** -70.0 - **Value:** -79.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -90.0 - **Spread:** - **Upper Limit:** -76.7 - **Value:** -82.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -89.8 - **Spread:** - **Upper Limit:** -84.2 - **Value:** -87.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -87.7 - **Spread:** - **Upper Limit:** -85.2 - **Value:** -86.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -88.3 - **Spread:** - **Upper Limit:** -83.0 - **Value:** -84.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -87.0 - **Spread:** - **Upper Limit:** -77.5 - **Value:** -83.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -86.9 - **Spread:** - **Upper Limit:** -80.0 - **Value:** -84.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -85.2 - **Spread:** - **Upper Limit:** -78.5 - **Value:** -81.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -87.5 - **Spread:** - **Upper Limit:** -80.9 - **Value:** -84.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -89.6 - **Spread:** - **Upper Limit:** -80.3 - **Value:** -84.9 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** Below the lower limit of quantification - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 24100 - **Upper Limit:** - **Value:** 19000 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 27300 - **Upper Limit:** - **Value:** 31600 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20600 - **Upper Limit:** - **Value:** 36400 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17300 - **Upper Limit:** - **Value:** 27500 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12400 - **Upper Limit:** - **Value:** 23300 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9700 - **Upper Limit:** - **Value:** 19900 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8900 - **Upper Limit:** - **Value:** 21400 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent \< 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The efficacy analysis set included participants with a Baseline histology assessment and at least 1 postdose histology assessment from weeks 5-25; or a Baseline radiology assessment and at least 1 postdose radiology assessment from weeks 5-25. Evaluable participants had to be on study for at least 28 days after administration of the first dose. **Reporting Status:** POSTED **Time Frame:** From enrollment until 25 weeks **Title:** Percentage of Participants With Giant Cell Tumor Response **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** OG000 **Title:** Denosumab #### Outcome Measure 2 **Description:** Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Efficacy Analysis Set with available data at each time point (n). **Reporting Status:** POSTED **Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 **Title:** Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** OG000 **Title:** Denosumab #### Outcome Measure 3 **Description:** Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Efficacy Analysis Set with available data at each time point (n). **Reporting Status:** POSTED **Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 **Title:** Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen) **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** OG000 **Title:** Denosumab #### Outcome Measure 4 **Description:** Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The pharmacokinetics analysis set included participants who received at least 1 dose of denosumab and for whom at least 1 serum denosumab trough concentration was available. 'n' indicates the number of participants with available data at each time point. **Reporting Status:** POSTED **Time Frame:** Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49. **Title:** Serum Denosumab Trough Concentrations **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** OG000 **Title:** Denosumab #### Outcome Measure 5 **Description:** An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug. **Parameter Type:** NUMBER **Population Description:** All participants who received at least 1 dose of denosumab. **Reporting Status:** POSTED **Time Frame:** From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months **Title:** Number of Participants With Adverse Events (AEs) **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** OG000 **Title:** Denosumab #### Outcome Measure 6 **Description:** Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study. **Parameter Type:** NUMBER **Population Description:** Participants who received at least 1 dose of denosumab and had at least 1 anti-denosumab antibody sample. **Reporting Status:** POSTED **Time Frame:** From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months. **Title:** Number of Participants With Anti-Denosumab Antibodies **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** OG000 **Title:** Denosumab ### Participant Flow Module #### Group **Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. **ID:** FG000 **Title:** Denosumab #### Period **Title:** Overall Study ##### Withdraw **Type:** Ongoing in study ###### Reason **Group ID:** FG000 **Number of Subjects:** 26 ##### Withdraw **Type:** Disease progression ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 37 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 7 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 30 **Recruitment Details:** First patient enrolled 10 July 2006; Last patient enrolled 25 January 2008. Results data are reported as of the data cut-off date of 07 April 2008. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02773979 **Brief Title:** PfSPZ Challenge in Healthy Malaria-Naïve Adults in the United States **Official Title:** A Phase 1 Dose Escalation Trial to Assess the Safety and Efficacy of Infectious (Replication-intact), Cryopreserved Plasmodium Falciparum Sporozoites (PfSPZ Challenge) Administered by Direct Venous Inoculation Under Chloroquine Cover (PfSPZ-CVac) on Varying Schedules in Healthy Malaria-Naïve Adults in the United States #### Organization Study ID Info **ID:** 11-0042 #### Organization **Class:** NIH **Full Name:** National Institute of Allergy and Infectious Diseases (NIAID) #### Secondary ID Infos **ID:** HHSN272201300019I ### Status Module #### Completion Date **Date:** 2018-01-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-12-27 **Type:** ACTUAL **Last Update Submit Date:** 2019-12-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-01-22 **Type:** ACTUAL #### Start Date **Date:** 2016-09-12 **Type:** ACTUAL **Status Verified Date:** 2017-04-05 #### Study First Post Date **Date:** 2016-05-16 **Type:** ESTIMATED **Study First Submit Date:** 2016-05-12 **Study First Submit QC Date:** 2016-05-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False ### Description Module **Brief Summary:** This phase I trial of the replication-intact PfSPZ Challenge vaccine given under CQ cover will enroll 28 healthy volunteers to receive PfSPZ or placebo, as well as suppressive doses of chloroquine (CQ)on varying schedules. 10 weeks post 3rd immunization subjects will be subjected to controlled human malarial infection. The primary objective of this study is to evaluate the safety and tolerability of escalating doses of Sanaria PfSPZ Challenge administered by DVI on varying schedules to healthy malaria-naïve adults taking suppressive doses of CQ (PfSPZ-CVac). **Detailed Description:** This phase I trial of the replication-intact PfSPZ Challenge vaccine given under CQ (PfSPZ-CVac) cover will randomize 28 healthy adult participants to one of three cohorts. Group 1 (n=12) will be randomized to receive PfSPZ Challenge vaccine at a dose of 51,200 sporozoites or 0.5 mL of sterile normal saline placebo by DVI on Days 3, 10 and 17. Group 2 (n=4) will be randomized to receive PfSPZ Challenge vaccine at a dose of 102,400 sporozoites or 0.5 mL of sterile normal saline placebo by DVI on Days 3, 10, and 17. Within both groups, placebo will be assigned 1:3, with blinded allocation to the two treatments within each group. All subjects in Study Groups 1 and 2 will receive, by directly observed treatment (DOT), oral chloroquine (CQ) on Days 1, 8, 15, and 22 at a suppressive dose of 600 mg base on Day 1 and 300 mg base on Days 8, 15 and 22. All subjects in Group 3 (n=9) will receive PfSPZ Challenge vaccine at a dose of 102,400 sporozoites per administration, with vaccine given on a Day 1, 6, and 11 schedule. Subjects in Group 3 will also receive, by DOT, oral CQ, with a suppressive dose of 600 mg base on Day 1 and a dose of 300 mg base on Days 6, 11, and 16. At 10 weeks after the third administration of study vaccine or placebo, all subjects within the three groups will receive the PfSPZ Challenge by direct venous injection at a dose of 3,200 P. falciparum sporozoites to assess vaccine efficacy against controlled human malarial infection (CHMI). The primary objective of this study is to 1) evaluate the safety and tolerability of escalating doses of Sanaria PfSPZ Challenge administered by DVI on varying schedules to healthy malaria-naïve adults taking suppressive doses of CQ (PfSPZ-CVac). ### Conditions Module **Conditions:** - Plasmodium Falciparum Infection **Keywords:** - challenge - malaria - P. falciparum - PfSPZ - sporozoites - vaccine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 28 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Chloroquine (CQ)/PfSPZ Challenge 51200 sporozoites or CQ/normal saline (NS). N=12, randomized 3:1 **Intervention Names:** - Drug: Chloroquine - Biological: PfSPZ (NF54) Challenge - Other: Placebo **Label:** Group 1: PfSPZ 51200 sporozoites/Placebo **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** CQ/PfSPZ Challenge 102400 sporozoites or CQ/NS. N=4, randomized 3:1 **Intervention Names:** - Drug: Chloroquine - Biological: PfSPZ (NF54) Challenge - Other: Placebo **Label:** Group 2: PfSPZ 102400 sporozoites/Placebo **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** CQ/PfSPZ Challenge 102400 sporozoites N=9 **Intervention Names:** - Drug: Chloroquine - Biological: PfSPZ (NF54) Challenge **Label:** Group 3: PfSPZ 102400 sporozoites **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1: PfSPZ 51200 sporozoites/Placebo - Group 2: PfSPZ 102400 sporozoites/Placebo - Group 3: PfSPZ 102400 sporozoites **Description:** Administered as 600mg PO, day 1, 300mg PO days 8, 15, 22. **Name:** Chloroquine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Group 1: PfSPZ 51200 sporozoites/Placebo - Group 2: PfSPZ 102400 sporozoites/Placebo - Group 3: PfSPZ 102400 sporozoites **Description:** Cryopreserved Plasmodium falciparum (Pf) fully infectious sporozoites (SPZ) that have been developed to be used to infect volunteers in controlled human malaria infection (CHMI) to assess the efficacy of antimalarial drugs and vaccines. The PfSPZ (NF54) Challenge contains a laboratory malaria strain isolated from a Dutch traveler to Africa. **Name:** PfSPZ (NF54) Challenge **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - Group 1: PfSPZ 51200 sporozoites/Placebo - Group 2: PfSPZ 102400 sporozoites/Placebo **Description:** Placebo **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** The number of serious adverse events (SAEs) related to study product. **Time Frame:** Days 1-203 **Measure:** The number of solicited local adverse events (AEs) **Time Frame:** Days 1-93 **Measure:** The number of solicited systemic adverse events(AEs) **Time Frame:** Day 1-116 **Measure:** The number of unsolicited adverse events (AEs) related to study product **Time Frame:** Days 1-130 **Measure:** The severity of solicited local adverse events (AEs) as assessed by grading scales **Time Frame:** Day 1-93 **Measure:** The severity of solicited systemic adverse event (AEs) as assessed by grading scales **Time Frame:** Day 1-116 **Measure:** The severity of unsolicited AEs related to study product as assessed by grading scales. **Time Frame:** Days 1-130 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy adults (males and non-pregnant, non-lactating females) between the ages of 18 and 45 years, inclusive. 2. Able and willing to participate for the duration of the study. 3. Able and willing to provide written (not proxy) informed consent. 4. Provides informed consent before any study procedures, correctly answers \>/= 70% of questions on the post consent quiz and is available for all study visits. 5. Women of childbearing potential\* must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to each vaccination and on the day of malaria challenge. * Not sterilized via bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or menopausal and still menstruating or \< 1 year of the last menses. 6. Women of childbearing potential must have used an acceptable method of contraception\* in the 30 days prior to enrollment and must agree to continue use of the same method throughout the study. * Includes, but is not limited to, abstinence from sex with men, monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to enrollment, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing, successful Essure placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure, and licensed hormonal methods such as implants, injectables, or oral contraceptives. 7. Is in good health, as judged by the investigator, and determined by vital signs (heart rate, blood pressure, and oral temperature), medical history and physical examination. 8. Able to understand and comply with planned study procedures. 9. Reachable (24/7) by mobile phone during the whole study period and willing to provide two close contacts to assist with making contact. 10. Lives in the greater Seattle area and within an approximately one hour commute to the study research clinic. 11. Willing to avoid non-study related blood donation for 3 years following P. falciparum challenge. 12. Agrees not to travel to a malaria endemic region during the entire course of the trial. 13. Agrees not to travel away from the greater Seattle area from the day of first study immunization through 20 days after the last study immunization, and during the 29 days after CHMI. Exclusion Criteria: 1. History of malaria infection or vaccination, residence in a malaria-endemic area for \> / =5 years, travel to a malaria-endemic area in the past 6 months, or participation in a malaria research study. 2. Is breastfeeding or plans to breastfeed at any time throughout the study. 3. Plans to become pregnant at any time throughout the study. 4. Use of any antimalarial antibiotic or drug within 28 days prior to Study Day 1 or planned use during the study period. 5. Any clinically significant acute or chronic medical condition\* or need for chronic medications\*\* that, in the opinion of the investigator, will interfere with immunity or affect safety. * Includes, but is not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions. * Receipt of systemic, prescription medications for the treatment of chronic medical conditions or variations of normal physiologic functions are permissible if, in the opinion of the investigator, they are used for conditions that are not clinically significant and would not impact the effectiveness of the vaccine or the safety of the subject or the safety and immunogenicity outcomes of the protocol. Use of systemic, over-the-counter medications and PRN systemic, prescription medications are allowed if, in the opinion of the investigator, they pose no additional risk to subject safety, vaccine efficacy or assessment of immunogenicity/reactogenicity. Topical (except corticosteroid) medications, nasal (including corticosteroid) medications, vitamins, and supplements are permissible. Any drug with antimalarial properties is not permissible. 6. Asthma, other than mild, well-controlled asthma\*. * Cold or exercise induced asthma controlled with inhaled medications other than inhaled corticosteroids is permissible. Subjects should be excluded if they require daily bronchodilator use, or have had an asthma exacerbation requiring oral/parenteral steroid use or have used theophylline or inhaled corticosteroids in the past year. 7. Diabetes mellitus. 8. History of a psychiatric condition that may make study compliance difficult, such as schizophrenia, or unstable bipolar disorder\*. * Includes persons with psychoses or history of suicide attempt or gesture in the 3 years before study entry or an ongoing risk for suicide. 9. Any history of non-febrile seizures or complex febrile seizures\* * History of simple febrile seizures or a family history of seizure disorder is not exclusionary 10. Autoimmune disease (autoimmune thyroid disease is permissible and vitiligo or mild eczema not requiring chronic therapy is permissible). 11. Known or suspected congenital or acquired immunodeficiency including anatomic or functional asplenia\* or immunosuppression as a result of underlying illness or treatment. \*Any splenectomy is exclusionary. 12. Abuse of alcohol or drugs that, in the opinion of the investigator, may interfere with the subject's ability to comply with the protocol. 13. Body mass index (BMI) \> / = 35 kg/m\^2. 14. Active neoplastic disease\*. * Subjects with a history of malignancy may be included if treated by surgical excision or if treated by chemotherapy or radiation therapy and has been observed for a period that in the investigator's estimation provides a reasonable assurance of sustained cure (not less than 36 months). 15. Chronic topical or systemic corticosteroid use\*. * Corticosteroid nasal sprays for allergic rhinitis are permissible. Persons using a topical corticosteroid for a limited duration for mild uncomplicated dermatitis such as poison ivy or contact dermatitis may be enrolled the day after their therapy is completed. Oral or parenteral (IV, SC, or IM) corticosteroids given for non-chronic conditions not expected to recur are permissible if, within the year prior to enrollment, the longest course of therapy was no more than 14 days and no oral or parenteral corticosteroids were given within 30 days prior to enrollment. Intraarticular, bursal, tendon, or epidural injections of corticosteroids are permissible if the most recent injection was at least 30 days prior to enrollment. 16. Receipt or planned receipt of inactivated vaccine or allergy desensitization injection from 14 days before the first immunization through 14 days after the last immunization. 17. Planned receipt of inactivated vaccine or allergy desensitization injection from 14 days prior to CHMI through 28 days after CHMI. 18. Receipt or planned receipt of live attenuated vaccine 30 days before or at any time during the study up to 28 days after CHMI. 19. Receipt of any experimental agent\* within 30 days prior to enrollment or planned receipt prior to the end of the study. * Vaccine, drug, biologic, device, blood product, or medication. 20. Plans to enroll in another clinical trial\* that could interfere with safety assessment of the investigational product at any time during the study period. * Includes trials that have a study intervention such as a drug, biologic, or device. 21. Receipt of blood products or immunoglobulin within six months prior to Study Day 1 or donation of a unit of blood within two months before Study Day 1. 22. Systolic blood pressure \> / = 161 mm Hg or diastolic blood pressure \> / = 96 mm Hg. 23. Resting heart rate \< 55 or \> 100 beats per minute. 24. Oral temperature \> / = 38 degrees C (100.4 degrees F). 25. Positive serology for HIV 1/2. 26. Positive hepatitis B surface antigen (HBsAg). 27. Positive antibody to hepatitis C virus (HCV). 28. Any Grade 1 or higher screening clinical lab value\* (see Toxicity Tables Section 9.2.3). * Screening clinical labs include blood tests (white blood cells \[WBC\], hemoglobin, platelets, creatinine, non-fasting glucose, potassium, alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase, and total bilirubin) and urine dipstick tests (protein, glucose, hemoglobin). Any Grade 1 or higher value for any screening test will exclude the subject from enrollment with the exception of hematuria \> / = 1 + detected during menses or other endometrial bleeding for females. In this situation, the test can be repeated if clinically warranted but is not considered an indicator of poor health status or increased risk and so is not a contraindication to enrollment. 29. Acute febrile illness (oral temperature \> / = 38 degrees C \[100.4 degrees F\]) or other acute illness within 3 days prior to vaccination (subject may be rescheduled). 30. A screening ECG with abnormalities consistent with underlying heart disease.\* * Pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial or ventricular contractions; right or left bundle branch block; QT/QTc interval \> 450 ms; or advanced (secondary or tertiary) A-V heart block. 31. Has a history of psoriasis or porphyria. 32. Has a known allergy to chloroquine, 4-aminoquinoline derivatives, atovaquone, proguanil,artemether-lumenfantrine, 8-aminoquinoline derivatives, non-steroidal anti- inflammatory drugs, or acetaminophen. 33. Is using or intends to use a medication that is cross-reactive with CQ\*\* or atovaquone and proguanil, such as cimetidine or metoclopramide, during the study period. * Antacids and kaolin can be administered at least 4 hours from intake of chloroquine. * Does not apply to infectivity controls 34. History of retinal or visual field changes, clinically significant auditory damage, or G6PD deficiency. 35. Has history of or a positive test for sickle cell disease or trait or other hemoglobinopathy. 36. Plans to undergo surgery (elective or otherwise) between enrollment and the end of the study. 37. Known hypersensitivity to PfSPZ or its components. 38. Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seattle **Country:** United States **Facility:** Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases **State:** Washington **Zip:** 98101-1466 ### References Module #### References **Citation:** Murphy SC, Deye GA, Sim BKL, Galbiati S, Kennedy JK, Cohen KW, Chakravarty S, Kc N, Abebe Y, James ER, Kublin JG, Hoffman SL, Richie TL, Jackson LA. PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: A randomized, placebo-controlled trial with controlled human malaria infection. PLoS Pathog. 2021 May 28;17(5):e1009594. doi: 10.1371/journal.ppat.1009594. eCollection 2021 May. **PMID:** 34048504 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011528 - Term: Protozoan Infections - ID: D000010272 - Term: Parasitic Diseases - ID: D000007239 - Term: Infections - ID: D000096724 - Term: Mosquito-Borne Diseases - ID: D000079426 - Term: Vector Borne Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M11280 - Name: Malaria - Relevance: HIGH - As Found: Malaria - ID: M14388 - Name: Protozoan Infections - Relevance: LOW - As Found: Unknown - ID: M13185 - Name: Parasitic Diseases - Relevance: LOW - As Found: Unknown - ID: M3255 - Name: Mosquito-Borne Diseases - Relevance: LOW - As Found: Unknown - ID: M2054 - Name: Vector Borne Diseases - Relevance: LOW - As Found: Unknown - ID: T3571 - Name: Malaria - Relevance: HIGH - As Found: Malaria ### Condition Browse Module - Meshes - ID: D000008288 - Term: Malaria ### Intervention Browse Module - Ancestors - ID: D000000563 - Term: Amebicides - ID: D000000981 - Term: Antiprotozoal Agents - ID: D000000977 - Term: Antiparasitic Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000000962 - Term: Antimalarials - ID: D000018501 - Term: Antirheumatic Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown - ID: M5979 - Name: Chloroquine - Relevance: HIGH - As Found: Metabolic Syndrome - ID: M244350 - Name: Chloroquine diphosphate - Relevance: LOW - As Found: Unknown - ID: M4280 - Name: Antimalarials - Relevance: LOW - As Found: Unknown - ID: M3904 - Name: Amebicides - Relevance: LOW - As Found: Unknown - ID: M4298 - Name: Antiprotozoal Agents - Relevance: LOW - As Found: Unknown - ID: M4294 - Name: Antiparasitic Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002738 - Term: Chloroquine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01159379 **Brief Title:** Safety of Ertapenem in Beta-lactam Allergic Patients. **Official Title:** Cross-reactivity and Tolerability of Ertapenem in Patients With IgE-mediated Allergy to Beta-lactams #### Organization Study ID Info **ID:** 1131/09 #### Organization **Class:** OTHER **Full Name:** Catholic University of the Sacred Heart ### Status Module #### Completion Date **Date:** 2011-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2011-01-05 **Type:** ESTIMATED **Last Update Submit Date:** 2011-01-04 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2011-09 **Type:** ESTIMATED #### Start Date **Date:** 2011-01 **Status Verified Date:** 2010-01 #### Study First Post Date **Date:** 2010-07-09 **Type:** ESTIMATED **Study First Submit Date:** 2010-06-03 **Study First Submit QC Date:** 2010-07-08 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Merck Sharp & Dohme LLC #### Lead Sponsor **Class:** OTHER **Name:** Catholic University of the Sacred Heart #### Responsible Party **Old Name Title:** Prof. Domenico Schiavino **Old Organization:** Catholic University of the Sacred Heart ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to assess cross-reactivity and tolerability of ertapenem in patients with IgE-mediated allergy to at least one beta-lactam molecule. **Detailed Description:** Ertapenem is a new carbapenem, stable to dehydropeptidase which has a broad antibacterial activity. Ertapenem exhibits a bactericidal mode of action and it has a long half-life of 4.5 hours; for this reason it can be developed as a single daily dose carbapenem. In literature, no cases of IgE-mediated allergy to ertapenem have been described until now. However, a single study put in evidence a 47% rate of cross-reactivity between imipenem-cilastatin and beta-lactams in a group of patients affected by IgE-mediated allergy to these drugs. For this reason carbapenem administration to beta-lactam allergic patients has always been considered potentially harmful. Other studies reported lower cross-reactivity rates (from 7 to 11%) between imipenem-cilastatin and beta-lactams but patients of these studies did not undergo any allergy testing in order to demonstrate the pathogenesis of the reactions. Recent studies put in evidence that imipenem has a very low cross-reactivity rate with other beta-lactams and they have a very good tolerability among patients with IgE-mediated allergy to beta-lactams: Romano et al. found a cross-reactivity rate of 0.9% between imipenem and penicillins in 112 penicillin-allergic patients (mean age 44.56 ± 15.66 ys.); Atanasković-Marković et al. found a cross-reactivity rate of 0.8% in 124 paediatric patients (age range 3-14 ys.) between imipenem and penicillins. In both groups imipenem was well tolerated by patients with negative allergy testing. Meropenem showed to have a good tolerability too in penicillin allergic patients: Romano et al. found a cross-reactivity rate of 0.9% between penicillins and meropenem in penicillin-allergic patients (mean age 47.83 ± 15.8); Atanasković-Marković et al. found a cross-reactivity rate of 0.8% in 109 paediatric patients (age range 3-14 ys.) between meropenem and penicillins. In both groups meropenem was well tolerated by patients with negative allergy testing. No data regarding the cross-reactivity of ertapenem with other beta-lactams and its tolerability among patients with IgE-mediated allergy beta-lactams are available in literature. Aim of the study On the basis of those data, we decided to investigate the cross-reactivity of ertapenem with other beta-lactams in patients suffering from IgE-mediated allergy to at least one beta-lactam molecule and its tolerability in a group of a patients with negative allergy testing with ertapenem. ### Conditions Module **Conditions:** - IgE-Mediated Hypersensitivity - Allergy **Keywords:** - IgE-mediated allergy - Beta-lactams - Ertapenem - Cross-reactivity - Immediate-type skin tests - Intravenous tolerance tests ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with IgE-mediated allergy to beta-lactams **Intervention Names:** - Drug: ertapenem **Label:** ertapenem, tolerance tests **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - ertapenem, tolerance tests **Description:** intravenous, 1 gram, once **Name:** ertapenem **Other Names:** - Invanz **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Cross-reactivity between beta-lactams and ertapenem. **Time Frame:** 1 day #### Secondary Outcomes **Measure:** Tolerability of ertapenem in patients with IgE-mediated allergy to beta-lactams. **Time Frame:** 1 day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * IgE-mediated allergy to at least one beta-lactam molecule Exclusion Criteria: * positive allergy testing to ertapenem * chronic diseases * treatment with beta-blockers * pregnancy **Maximum Age:** 75 Years **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** dschiavino@rm.unicatt.it **Name:** Domenico Schiavino, MD **Phone:** 0630155896 **Phone Ext:** +39 **Role:** CONTACT **Contact 2:** **Email:** alessandrobuonomo@hotmail.com **Name:** Alessandro Buonomo, MD **Phone:** 0630155896 **Phone Ext:** +39 **Role:** CONTACT #### Locations **Location 1:** **City:** Rome **Contacts:** ***Contact 1:*** - **Email:** dschiavino@rm.unicatt.it - **Name:** Domenico Schiavino, MD - **Role:** CONTACT ***Contact 2:*** - **Email:** alessandrobuonomo@hotmail.com - **Name:** Alessandro Buonomo, MD - **Role:** CONTACT ***Contact 3:*** - **Name:** Domenico Schiavino - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Italy **Facility:** Allergy Department, Catholic University of the Sacred Heart **Zip:** 00168 #### Overall Officials **Official 1:** **Affiliation:** Allergy Department, Catholic University of the Sacred Heart **Name:** Domenico Schiavino, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10018 - Name: Hypersensitivity - Relevance: HIGH - As Found: Hypersensitivity - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: HIGH - As Found: IgE-Mediated Hypersensitivity - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006967 - Term: Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate ### Intervention Browse Module - Ancestors - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10789 - Name: Lactams - Relevance: LOW - As Found: Unknown - ID: M25772 - Name: beta-Lactams - Relevance: LOW - As Found: Unknown - ID: M1887 - Name: Ertapenem - Relevance: HIGH - As Found: Egypt - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077727 - Term: Ertapenem ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04198779 **Acronym:** APPLIMONCOEUR **Brief Title:** Interest of the Smartphone Application "MonCœur" in the Follow-up of Patients With Heart Failure **Official Title:** Interest of the Smartphone Application "MonCœur" in the Follow-up of Patients With Heart Failure #### Organization Study ID Info **ID:** 2019-01 #### Organization **Class:** OTHER **Full Name:** French Cardiology Society ### Status Module #### Completion Date **Date:** 2023-11-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-01 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-28 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2023-11-27 **Type:** ACTUAL #### Start Date **Date:** 2020-02-12 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2019-12-13 **Type:** ACTUAL **Study First Submit Date:** 2019-12-06 **Study First Submit QC Date:** 2019-12-12 **Why Stopped:** Low recrutement rate ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** French Cardiology Society #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Heart failure is a chronic disease that requires careful monitoring and therapeutic education. Smartphones have made their appearance in patients lives and allow close contact with them. The possibility of using a digital application dedicated to patients with heart failure concerning the symptoms to be monitored, treatments, diet, appointments, physical activity could improve the monitoring and the prognosis of patients following their hospitalization. **Detailed Description:** The aim of this study is to demonstrate that the use of a special application dedicated to the monitoring of heart failures disease has a favorable impact on the occurrence of readmissions and, ultimately, cardiovascular mortality. The aim of this study is also to demonstrate that the use of this "MonCœur" application improves symptoms, quality of life, treatment compliance, diet compliance, and physical activity in patient with heart failure disease. ### Conditions Module **Conditions:** - Heart Failure - Heart Decompensation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Prospective, multicentric, randomized, controlled, open, 2 parallel arms study, in 11 centers. ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 125 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Care support with implementation of the application **Intervention Names:** - Device: APPLI **Label:** APPLI **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Conventional care support **Label:** CONTROL **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - APPLI **Description:** The support with the digital application is including a 10-minutes training about the use of the digital application at the beginning of the study. Patient will have to register information about their Heart failure disease (weight, shortness of breath, fatigue, mood, cardiologist appointments, blood results, ...). During each routine consultation, patients will be encouraged to use the digital app, and the obstacles encountered will be explored and resolved. In addition, participants will receive an email containing relevant information and, every three months, an email reminder of the use of the application. **Name:** APPLI **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Comparison between the 2 study arms of the score of the European Heart Failure Self-care Behaviour Scale, consisting of 9 items each evaluated on a 5-point Likert scale, and allowing the calculation of a standardized global score from 0 to 100: the highest score indicating better "self-care". **Measure:** Evaluation of the use of "MonCoeur" application on the impact of patient health self-care **Time Frame:** 3, 6 and 12 months #### Secondary Outcomes **Description:** Comparison between the 2 study arms on the number of days without hospitalisation **Measure:** Evaluation of the use of "MonCoeur" application on hospitalisation rate **Time Frame:** 3, 6 and 12 months **Description:** Comparison between the 2 study arms of Brain Natriuretic Peptid (nanograms / liter) **Measure:** Evaluation of the use of "MonCoeur" application on cardiovascular parameters **Time Frame:** 3, 6 and 12 months **Description:** Comparison between the 2 study arms on percentage of appointments scheduled versus appointments honored. Comparison between the 2 study arms of the score of the treatment observance scale Ameli. **Measure:** Evaluation of the use of "MonCoeur" application on patient compliance **Time Frame:** 3, 6 and 12 months **Description:** Comparison between the 2 study arms of the score of the Minnesota Living with Heart Failure Questionnaire. It provides a total score (range 0-105, from best to worst), as well as scores for two dimensions, physical (8 items, range 0-40) and emotional (5 items, range 0-25). The other eight items (of the total of 21) are only considered for the calculation of the total score. **Measure:** Evaluation of the use of "MonCoeur" application on patient quality of life: Minnesota Living with Heart Failure Questionnaire **Time Frame:** 3, 6 and 12 months **Description:** Comparison between the 2 study arms of the score of the Qappa ("questionnaire d'activité physique pour personnes âgées" / translation in english: "physical activity questionnaire for seniors") physical activity questionnaire. The QAPPA uses the calculation system of the volume of physical activity per minute and per week and classified as high, moderate, or low level. **Measure:** Evaluation of the use of "MonCoeur" application on patient physical activity **Time Frame:** 3, 6 and 12 months **Description:** Calculation of the number and type of parameters filled in the application. **Measure:** Describe how often and how the application is used by patients **Time Frame:** 3, 6 and 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient hospitalized for acute or decompensated heart failure * Patient with a smartphone and able to use a digital application * Beneficiary of a social protection scheme * Patients benefiting from a telemedicine program can be included Exclusion Criteria: * Acute coronary syndrome during ongoing hospitalization. * Acute myocarditis, constrictive pericarditis, acute endocarditis during ongoing hospitalization. * Isolated right heart failure of respiratory origin. * Existence of a cause considered rapidly reversible to acute heart failure: tachyarrhythmia, excessive bradycardia, acute anemia, acute renal failure, malignant hypertension, overdose or cardiotoxic drug intoxication. * Indication of cardiac surgery scheduled within 3 months after hospitalization, patients with Tavi or MItraclip expected within 3 months * Extracardiac disease with short-term prognosis (progressive neoplasia). * Refusal or incapacitation of language or psychic to sign informed consent * Patients participating in an other biomedical research can not participate in this study for the first 6 months, not to interfere with the consultation process of the study. * Pregnant or lactating women can't participate in the study. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Amiens **Country:** France **Facility:** CHU Amiens - Picardie - Site Sud **Zip:** 80054 **Location 2:** **City:** Bron **Country:** France **Facility:** Hospices Civils de Lyon **Zip:** 69677 **Location 3:** **City:** Créteil **Country:** France **Facility:** CHU Henri Mondor **Zip:** 94010 **Location 4:** **City:** Grenoble **Country:** France **Facility:** CHU de Grenoble **Zip:** 38043 **Location 5:** **City:** Le Kremlin-Bicêtre **Country:** France **Facility:** Hôpital Bicêtre **Zip:** 94275 **Location 6:** **City:** Lille **Country:** France **Facility:** CHRU de Lille **Zip:** 59037 **Location 7:** **City:** Melun **Country:** France **Facility:** Groupe Hospitalier Sud Ile de France **Zip:** 77000 **Location 8:** **City:** Montpellier **Country:** France **Facility:** CHU Arnaud de Villeneuve **Zip:** 34295 **Location 9:** **City:** Paris **Country:** France **Facility:** Hôpital Lariboisière **Zip:** 75010 **Location 10:** **City:** Paris **Country:** France **Facility:** Hôpital Universitaire Pitié Salpêtrière **Zip:** 75651 **Location 11:** **City:** Paris **Country:** France **Facility:** Hôpital Européen Georges Pompidou **Zip:** 75908 **Location 12:** **City:** Poitiers **Country:** France **Facility:** CHU de Poitiers **Zip:** 86021 **Location 13:** **City:** Rouen **Country:** France **Facility:** CHU de ROUEN - Hôpital Charles Nicolle **Zip:** 76031 **Location 14:** **City:** Strasbourg **Country:** France **Facility:** CHRU de Strasbourg **Zip:** 67091 **Location 15:** **City:** Toulon **Country:** France **Facility:** Hôpital Sainte Musse de Toulon **Zip:** 83100 **Location 16:** **City:** Toulouse **Country:** France **Facility:** CHU de Toulouse **Zip:** 31059 #### Overall Officials **Official 1:** **Affiliation:** Hôpital Bicêtre **Name:** Emmanuelle BERTHELOT, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01594879 **Brief Title:** Treatment With Medroxyprogesterone Acetate Plus LNG-IUS in Young Women With Early Stage Endometrial Cancer **Official Title:** Treatment With Medroxyprogesterone Acetate(MPA) Plus Levonorgestrel-releasing Intrauterine System(LNG-IUS) in Young Women With Early Stage Endometrial Cancer: Multicenter Study: Korean Gynecologic Oncology Group Study (KGOG2009) #### Organization Study ID Info **ID:** KGOG2009 #### Organization **Class:** OTHER **Full Name:** Korean Gynecologic Oncology Group ### Status Module #### Completion Date **Date:** 2014-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2012-05-09 **Type:** ESTIMATED **Last Update Submit Date:** 2012-05-08 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2014-12 **Type:** ESTIMATED #### Start Date **Date:** 2012-01 **Status Verified Date:** 2012-05 #### Study First Post Date **Date:** 2012-05-09 **Type:** ESTIMATED **Study First Submit Date:** 2012-05-07 **Study First Submit QC Date:** 2012-05-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Korean Gynecologic Oncology Group #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** A prospective multicenter trial has been started in Korea to investigate the treatment efficacy of Levonorgestrel-releasing intrauterine system (LNG-IUS) plus Medroxyprogesterone Acetate(MPA) in Young Women with Early Stage Endometrial Cancer. The standard treatment for endometrial cancer is total hysterectomy and bilateral salpingo-oophorectomy, peritoneal cytology, and lymph node dissection. However, young patients who desire to preserve their potential for fertility may find this standard treatment difficult to accept. Therefore, the conservative treatment for these patients has remained a challenge. A number of studies have reported the effectiveness of hormonal therapy using systemic progestin in women clinically diagnosed with early endometrial adenocarcinoma at stage IA, grade 1, who want to maintain reproductive potential. In addition, several recent studies reported the use of LNG-IUS to treat patients at a high risk of perioperative complications who cannot tolerate systemic progesterone because of its adverse effects. Nevertheless, there has been no prospective multicenter trial that investigated the effectiveness of treatment with systemic progesterone in combination with intrauterine progesterone in young women with endometrial cancer. Therefore, the investigators conducted a prospective trial of the treatment of the presumably early-stage grade 1 endometrial cancer in young women who desire to preserve fertility by using oral MPA in combination with LNG-IUS. Young patients with histologically confirmed grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium, who desired to preserve fertility potential go through LNG-IUS insertion and are administered MPA at a dosage of 500 mg/d concurrently. Follow-up and treatment response assessment were implemented at a 3-month interval with office endometrial aspiration biopsy with LNG-IUS in place and dilatation and curettage after removal of LNG-IUS. The primary endpoint is response rate. Secondary endpoint is to estimate the consistency of the results between office endometrial aspiration biopsy and dilatation and curettage (D\&C) procedure. **Detailed Description:** PURPOSE: This prospective study aims to analyze the treatment efficacy of LNG-IUS plus MPA in Young Women with Early Stage Endometrial Cancer and to analyze the diagnostic accuracy of office endometrial aspiration biopsy with LNG-IUS in place compared with dilatation and curettage after removal of LNG-IUS. ENDPOINTS: The primary endpoints of this study is response rate. Secondary endpoint is to estimate the consistency of the results between office endometrial aspiration biopsy and dilatation and curettage (D\&C) procedure. STUDY SETTING AND PROTOCOL REVIEW: This study is a single arm, prospective multi-institutional study. Its protocol was approved by the Institutional Review Board of each clinical trial institution. PLANNED CLINICAL TRIAL PERIOD: Patient Selection and Enrollment: 24 month after IRB approval of clinical trial Institution. TREATMENT METHODS: Patients with histologically confirmed grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium went through LNG-IUS insertion and were administered MPA at a dosage of 500 mg/day concurrently. Follow-up and treatment response assessment were implemented at a 3-month interval with transvaginal ultrasonography, endometrial aspiration biopsy with LNG-IUS in place and D\&C after removal of LNG-IUS. The biopsy findings are compared. INVESTIGATIONAL PRODUCT 1. General Name/Brand name: Mirena - SCHERING Active ingredient: levonorgestrel 52mg Description: Mirena is a hormone-releasing T-shaped intrauterine system. A removal thread is attached to a loop at the end of the vertical stem of the T-body. 2. General Name/Brand name:Farlutal tab. 500mg/ Pfizer Active ingredient: Medroxyprogesterone Acetate PLANNED NUMBER OF SUBJECT 39 patients with biopsy proven grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium. STATISTICAL CONSIDERATIONS The primary objective of this study is to estimate the treatment efficacy of the oral MPA in combination with LNG-IUS in early stage endometrial cancer in terms of their response rate. The sample size needed for this estimation would be 39 patients after considering 10% of follow-up loss. The Secondary objective is to estimate the consistency of the office endometrial aspiration biopsy and D\&C. Kappa statistics will be used ### Conditions Module **Conditions:** - Endometrial Cancer **Keywords:** - Endometrial cancer - LNG-IUS - oral MPA ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 39 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Device: MIrena(LNG-IUS), oral MPA **Label:** Endometrial cancer, LNG-IUS with MPA **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Endometrial cancer, LNG-IUS with MPA **Description:** 1. General Name/Brand name: Mirena - SCHERING Active ingredient: levonorgestrel 52mg Description: Mirena is a hormone-releasing T-shaped intrauterine system. A removal thread is attached to a loop at the end of the vertical stem of the T-body. 2. General Name/Brand name:Farlutal tab. 500mg/ Pfizer Active ingredient: Medroxyprogesterone Acetate **Name:** MIrena(LNG-IUS), oral MPA **Other Names:** - Mirena - Farlutal **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Young patients with histologically confirmed grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium, who desired to preserve fertility potential go through LNG-IUS insertion and are administered MPA at a dosage of 500 mg/d concurrently. Follow-up and treatment response assessment were implemented at a 3-month interval with office endometrial aspiration biopsy with LNG-IUS in place and dilatation and curettage after removal of LNG-IUS. **Measure:** response rate **Time Frame:** 24months after LNG-IUS insertion with taking oral MPA #### Secondary Outcomes **Description:** consistency of the results between office endometrial aspiration biopsy and dilatation and curettage (D\&C) procedure. **Measure:** consistency of the results between office endometrial aspiration biopsy and dilatation and curettage (D&C) procedure. **Time Frame:** every 3 month after LNG-IUS insertion with taking oral MPA ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patients younger than 40 years 2. Patients who are histological confirmed as endometrial adenocarcinoma grade I that is presumably confined to the endometrium based on the MRI evaluation 3. Patients who desire to preserve fertility potential 4. Patients signed the written informed consent voluntarily Exclusion Criteria: 1. Patients who have severe underlying disease or complication 2. Under treatment of metastatic cancer from other organs or less than 5 years after previous cancer therapy 3. Acute liver disease or kidney disease 4. Thrombosis or phlebothrombosis requiring treatment, Hyperlipidemia, Smoker **Maximum Age:** 40 Years **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seoul **Contacts:** ***Contact 1:*** - **Email:** sjseongcheil@yahoo.co.kr - **Name:** seok ju Seong - **Role:** CONTACT **Country:** Korea, Republic of **Facility:** Gangnam CHA medical center **State:** Gamnamgu **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Gangnam CHA medical center **Name:** Seok Ju Seong, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Kim MK, Seong SJ, Kang SB, Bae DS, Kim JW, Nam JH, Lim MC, Lee TS, Kim S, Paek J. Six months response rate of combined oral medroxyprogesterone/levonorgestrel-intrauterine system for early-stage endometrial cancer in young women: a Korean Gynecologic-Oncology Group Study. J Gynecol Oncol. 2019 Mar;30(2):e47. doi: 10.3802/jgo.2019.30.e47. Epub 2019 Jan 7. **PMID:** 30740964 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014594 - Term: Uterine Neoplasms - ID: D000005833 - Term: Genital Neoplasms, Female - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000014591 - Term: Uterine Diseases - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M19235 - Name: Endometrial Neoplasms - Relevance: HIGH - As Found: Endometrial Cancer - ID: M17342 - Name: Uterine Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8945 - Name: Genital Neoplasms, Female - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17339 - Name: Uterine Diseases - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000016889 - Term: Endometrial Neoplasms ### Intervention Browse Module - Ancestors - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000003270 - Term: Contraceptive Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000003271 - Term: Contraceptive Agents, Female - ID: D000003280 - Term: Contraceptives, Oral, Synthetic - ID: D000003276 - Term: Contraceptives, Oral ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M19256 - Name: Levonorgestrel - Relevance: HIGH - As Found: Adult diffuse large cell lymphoma - ID: M19554 - Name: Medroxyprogesterone Acetate - Relevance: LOW - As Found: Unknown - ID: M11508 - Name: Medroxyprogesterone - Relevance: LOW - As Found: Unknown - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M2116 - Name: Contraceptive Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016912 - Term: Levonorgestrel ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05384379 **Brief Title:** Efficacy and Safety Evaluation of BZ371B in ARDS Patients **Official Title:** Clinical Study to Evaluate the Efficacy and Safety od BZ371B in Patients With Acute Respiratory Distress System (ARDS) in Mechanical Ventilation, Due to Respiratory Infections #### Organization Study ID Info **ID:** BZ371CLI301 #### Organization **Class:** INDUSTRY **Full Name:** Biozeus Biopharmaceutical S.A. ### Status Module #### Completion Date **Date:** 2023-03-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-01 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-30 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2023-03-03 **Type:** ACTUAL #### Start Date **Date:** 2022-11-23 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2022-05-20 **Type:** ACTUAL **Study First Submit Date:** 2022-05-17 **Study First Submit QC Date:** 2022-05-17 **Why Stopped:** Suboptimal enrollment ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** InCor Heart Institute #### Lead Sponsor **Class:** INDUSTRY **Name:** Biozeus Biopharmaceutical S.A. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate safety, tolerability and efficacy of BZ371B in intubated patients with severe Acute Respiratory Distress Syndrome. **Detailed Description:** Acute respiratory distress syndrome (ARDS) is a severe medical condition that is triggered by an alveolar capillary membrane damage resulted from several causes. Among these causes, respiratory viral infections such as SARS-CoV-2 can be responsible for the development of the disease. ARDS presents a high mortality rate, which may range from 33-52%. The main difficulty for the treatment of this disease is dealing with hypoxia. Nitric Oxide inhalation therapy has proven to increase oxygenation and Ventilation/Perfusion by it's vasodilation property. However, there are several limitations for it's use, such as the need of a specialized equipment, systemic side effects, etc. The use of others vasodilation medications are not indicated due to their systemic systemic exposure and non-selective vasodilation. BZ371B is a small peptide that acts as a NO synthase (NOS) enhancer, inducing local NO production, and is capable to present local vasodilation effect increasing blood flow regulation, by a new and innovative mechanism of action. ### Conditions Module **Conditions:** - ARDS - ARDS, Human - Pulmonary Disease **Keywords:** - ARDS - Acute respiratory distress syndrome - Intubation - intubated - critical care - Nitric Oxide - NO - NOS - Nitric Oxide Synthase - BZ371B ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1 **Type:** ACTUAL **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intubated patients treated with inhaled BZ371B will receive a dose of 12 mg of BZ371B divided in two different nebulizations per day, for three cosnecutive days **Intervention Names:** - Drug: Inhaled BZ371B **Label:** Treated Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treated Group **Description:** Intubated patients suffering from ARDS will receive BZ371B in a dose of 12 mg. This will be divided into 2 nebulizations, each with 10 ml. The first nebulization is at a dose of 3 mg and the second at a dose of 9 mg. **Name:** Inhaled BZ371B **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** PaO2 divided by FiO2 measurement **Measure:** P/F ratio **Time Frame:** 4 days **Description:** Shunt ratio measurement **Measure:** Shunt ratio **Time Frame:** 4 days **Description:** V/Q measurement **Measure:** Ventilation-Perfusion (V/Q) ratio **Time Frame:** 4 days **Description:** SBP measurement **Measure:** Systemic blood pressure (SBP) **Time Frame:** 4 days **Description:** Heart Rate (HR) and Ejection Fraction measurement **Measure:** Cardiac Function **Time Frame:** 4 days **Description:** Adverse effect evaluation of compound use and application **Measure:** Adverse Effect **Time Frame:** 4 days #### Secondary Outcomes **Description:** PAP measurement **Measure:** Pulmonary arterial pressure (PAP) **Time Frame:** 4 days **Description:** Pulmonary vascular resistance measurement **Measure:** Pulmonary vascular resistence **Time Frame:** 4 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18 years old or older * Men or Women * In Mechanical Ventilation * Diagnosed with Acute Respiratory Dystress Syndrome characterized by: acute beginning (less than one week from the beggining of the disease); bilateral opacity in the Torax X-Ray (not explained by stroke, atelectasis or nodules); respiratory failure not derived from cardiac failure and water overload. * P/F lower or equal to 150 mmHg with FiO2 higher or equal to 70% and PEEP higher or or equal to 88 mmHg * ALready executed first pronation, followed by supine position. One hour after returning from supine position. Exclusion Criteria: * Presence of pulmonary thromboembolism * Presence of secondary bacterial pneumonia * Severe Asthma * Pregnant or lactanting women **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** São Paulo **Country:** Brazil **Facility:** InCor USP **Zip:** 05403-900 #### Overall Officials **Official 1:** **Affiliation:** Department of Cardio-Pulmonar, Pulmonary Division, Hospital das Clínicas, University of São Paulo **Name:** Marcelo BP Amato, Phd **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000012120 - Term: Respiration Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC01 - Name: Infections - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14965 - Name: Respiratory Distress Syndrome - Relevance: HIGH - As Found: ARDS, Human - ID: M14964 - Name: Respiratory Distress Syndrome, Newborn - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M28144 - Name: Acute Lung Injury - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: T4927 - Name: Respiratory Distress Syndrome, Infant - Relevance: LOW - As Found: Unknown - ID: T192 - Name: Acute Respiratory Distress Syndrome - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012128 - Term: Respiratory Distress Syndrome ### Intervention Browse Module - Browse Branches - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12507 - Name: Nitric Oxide - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04309279 **Brief Title:** Zentangle on Psychological Well-being **Official Title:** The Effects of Zentangle on Psychological Well-being Among Adults in Hong Kong: A Pilot Randomized Controlled Trial #### Organization Study ID Info **ID:** PSY011 #### Organization **Class:** OTHER **Full Name:** Chinese University of Hong Kong ### Status Module #### Completion Date **Date:** 2020-07-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-01-15 **Type:** ACTUAL **Last Update Submit Date:** 2021-01-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-06-30 **Type:** ACTUAL #### Start Date **Date:** 2020-04-11 **Type:** ACTUAL **Status Verified Date:** 2021-01 #### Study First Post Date **Date:** 2020-03-16 **Type:** ACTUAL **Study First Submit Date:** 2020-03-09 **Study First Submit QC Date:** 2020-03-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chinese University of Hong Kong #### Responsible Party **Investigator Affiliation:** Chinese University of Hong Kong **Investigator Full Name:** Fiona YY Ho **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study will examine the effects of Zentangle as an intervention for reducing stress and enhancing psychological wellbeing among Hong Kong adults. Zentangle is a mindful doodling process in which participants draw repetitive, structured patterns on small pieces of paper. The patterns consist of combinations of dots, lines, and curves. Zentangle is developed in 2003 by two Americans, and this concept is still new to many people. Some studies suggested that Zentangle can be effective in reducing stress and anxiety, but the number of research papers on Zentangle is limited. Although Zentangle has become a rather popular stress relief activity in Hong Kong recently due to its easiness to learn and minimal tool requirement, there is no related study on its effectiveness in promoting psychological wellbeing in Hong Kong. **Detailed Description:** This study will be a pilot randomized controlled trial on the effects of Zentangle as an intervention for reducing stress and enhancing psychological wellbeing among Hong Kong adults. Prior to all study procedures, an online informed consent (with phone support) will be obtained from potential participants. Around 30 eligible participants will be randomly assigned to either the Zentangle group or the waitlist control group in a ratio of 1:1. ### Conditions Module **Conditions:** - Mental Health Wellness **Keywords:** - Zentangle - Mindful doodling - Mindfulness - Psychological Well-being ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** The randomization will be performed by an independent assessor using a computer-generated list of numbers. A 2-hour online Zentangle class will be delivered to the Zentangle group by a certified Zentangle teacher via online webinar. The Zentangle group will complete a short qualitative questionnaire and participate in a 15-minute brief discussion right after the Zentangle class. They will also be encouraged to practice Zentangle daily for two weeks. Both Zentangle group and waitlist control group will complete a set of online questionnaires before the intervention commences, immediately after the intervention and 2 weeks after the intervention. An online Zentangle class will be provided to the waitlist control group after the post-intervention data of the Zentangle group has been collected. ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 38 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: Zentangle **Label:** Zentangle group **Type:** EXPERIMENTAL #### Arm Group 2 **Label:** Wait-list Control Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Zentangle group **Description:** Zentangle is a mindful doodling process in which participants draw repetitive, structured patterns on small pieces of paper. The patterns consist of combinations of dots, lines, and curves. **Name:** Zentangle **Other Names:** - Mindful doodling **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** PANAS is a 20-item scale, comprises of two 10-item subscales measuring positive affect (PA) and negative affect (NA). This self-report measure is being widely used in both clinical and community settings. A 5-point Likert scale is employed, ranging from "very slightly or not at all" to "extremely", to measure the extent to which participants have experienced such feelings over a specific period of time. **Measure:** Change in Positive and Negative Affect Schedule (PANAS) **Time Frame:** Baseline (Pre-intervention), immediately after intervention and 2-week post-intervention #### Secondary Outcomes **Description:** DASS-21 is a 21-items scale, comprises of three sub-scales which measures the negative emotional states of depression, anxiety, and stress. The DASS is based on a dimensional rather than a categorical conception of psychological disorder; thus, it has no direct implications for the allocation of patients to discrete diagnostic categories. However, recommended cutoff scores for conventional severity labels (normal, moderate, severe) are given in the DASS Manual. **Measure:** Change in Depression Anxiety Stress Scales-21 (DASS-21) **Time Frame:** Baseline (Pre-intervention) and 2-week post-intervention **Description:** The FFMQ-SF is a 24-item scale that is used to evaluate one's dispositional tendency to be mindful in daily life. Ratings on the 5-point Likert scale are obtained on 5 factors, including acting with awareness, describing, nonjudging, nonreactivity and observing. The 5-point scale ranging from "never or rarely true" to "very often or always true" is used to rate how frequent the participants had each experience. **Measure:** Five Facet Mindfulness Questionnaire-Short Form (FFMQ-SF) **Time Frame:** Baseline (Pre-intervention) and 2-week post-intervention **Description:** SCS-SF is a 12-item scale to evaluates the degree of self-compassion. Ratings on the 5-point Likert scale are obtained on 6 factors, including self-kindness, common humanity, mindfulness, selfjudgment, isolation and over-identification. The self-report 12-item SCS-SF explicitly represents the thoughts, emotions, and behaviors associated with self-compassion and includes items that measure how often people respond to feelings of inadequacy or suffering with each of six components. **Measure:** Self-Compassion Scale-Short Form (SCS-SF) **Time Frame:** Baseline (Pre-intervention) and 2-week post-intervention **Description:** ISI is a 7-item scale designed to evaluate perceived insomnia severity. Ratings on the 5-point Likert scale are obtained on the perceived severity of sleep-onset, sleep-maintenance, early morning awakening problems, satisfaction with current sleep pattern, interference with daily functioning, noticeably of impairment attributed to the sleep problem, and level of distress caused by the sleep problem. **Measure:** Insomnia Severity Index (ISI) **Time Frame:** Baseline (Pre-intervention) and 2-week post-intervention **Description:** Treatment evaluation form and engagement questionnaire will be used to collect participants' view on the Zentangle class and how often they practiced Zentangle for the past 2 weeks respectively. **Measure:** Treatment evaluation form and engagement questionnaire **Time Frame:** Immediately after intervention and 2-week post-intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Hong Kong residents 2. Aged from 18 to 65 3. Cantonese language fluency 4. Willingness to provide informed consent and comply with the trial protocol 5. Be able to join online webinar via a computer Exclusion Criteria: 1. Have suicidal ideation 2. Are using medication or psychotherapy for any psychiatric disorder 3. Experiencing depression and anxiety 4. Have major psychiatric, medical or neurocognitive disorders that make participation infeasible based on the research team's judgment 5. Are currently participating in a mindfulness practice **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Sha Tin **Country:** Hong Kong **Facility:** The Chinese University of Hong Kong ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02364479 **Brief Title:** Treatment of Axial Spondyloarthritis by Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein **Official Title:** Treatment of Active Axial Spondyloarthritis by Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection: a Randomized, Double-blind, Multicentral Clinical Trial to Investigate the Efficacy and Safety of Yisaipu® #### Organization Study ID Info **ID:** [2013]2-21 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2016-08-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-12-19 **Type:** ACTUAL **Last Update Submit Date:** 2019-12-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-07-28 **Type:** ACTUAL #### Start Date **Date:** 2014-02-10 **Type:** ACTUAL **Status Verified Date:** 2019-12 #### Study First Post Date **Date:** 2015-02-18 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-10 **Study First Submit QC Date:** 2015-02-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** Gu Jieruo **Investigator Title:** Division of Rheumatology of Third Affiliated Hospital of Sun Yat-sen University **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a randomized, double-blind, multicentral clinical trial to investigate the efficacy and safety of Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc fusion protein injection (Yisaipu®) in the treatment of active axial spondyloarthritis(SpA). The primary purpose is to assess the different situations in maintaining treatment programme in SpA patients with controlled inflammation by Yisaipu®. And the second purpose is to assess the eficacy and safety of Yisaipu® in axial SpAs. The trial will include 150 patients with stable NSAIDs therapy, and at the first stage they will receive 24-week full-dose of Yisaipu®. Then at the second stage the patients who achieve low disease activity (LDA, ASDAS\<2.1) at 24th week will be randomizedly divided into three group: full-dose of Yisaipu® group, half-dose of Yisaipu® group and placebo group. And the blind stage will last for 48 weeks. Patients who complete the 72-week therapy or achieve disease-flare criteria during the blind stage would finish the study. **Detailed Description:** This randomised controlled trial enrolled adult patients aged 18 years or older diagnosed with non-radiographic axial spondyloarthritis at 3 centres in China. Patients had to fulfil ASAS axial spondyloarthritis criteria but could not fulfil the modified New York radiologic criterion for ankylosing spondylitis,and had to have objective evidence of active inflammation or chronic structral change，such as bone erosion or fat metaplasia in the sacroiliac joints on MRI at screening. Active disease activity was defined as a disease activity score in ASDAS-CRP ≥2.1,or Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] ≥4 on a numerical rating scale of 0-10, and an inadequate response to more than one non-steroidal anti-inflammatory drugs (NSAIDs) for 4 weeks at least, intolerance to NSAIDs, or contraindication for NSAIDs. No change in NSAIDs dose was required from 2 weeks before screening to the end of the study. Dose stability or discontinuation was required for 4 weeks before baseline for concomitant DMARDs or corticosteroids (prednisone or equivalent at a dose of less than 10 mg/day). Chinese herbal medicine, physical therapy, or live (attenuated) vaccine, or intravenous immunoglobulin IgG, was required for discontinuation and wash period for at least 4 weeks. Patients were excluded if they had previously taken or were taking biologic treatment, any biologic Dmards such as IL-6 or CD-20 inhibitors. Patients with latent tuberculosis infection were included only when local guidelines were followed for prophylactic treatment and if treatment was initiated before Yisaipu. All patients provided written informed consent, and the study protocol was approved by an institutional review board or independent ethics committee at each study site. The study was conducted in accordance with applicable regulations and the ethical principles of Good Clinical Practice as defined by the International Conference on Harmonisation (ICH) and the Declaration of Helsinki. A randomized envelope was used to enrol all patients at the baseline visit and to randomly assign qualifying patients in a 1:1:1 ratio to receive either blinded Yisaipu 50 mg subcutaneously every week or 25 mg subcutaneously every week or matching placebo at week 24. All study personnel, including the sponsor (with the exception of the Sanshengguojian drug supply management team), investigator, and study site personnel, and the patient remained blinded to treatment throughout the double-blinded period from week 24 through week 72 of the study. Investigational products were provided to maintain blinding. In the initial open-label period, enrolled patients were given subcutaneous injections of 50 mg Yisaipu every week for 36 weeks. Participants were given the dose of NSAIDs they had been receiving at screening; a dose decrease or discontinuation was allowed when the patients were intolerance to NSAIDs, or contraindication for NSAIDs. Patients who achieved clinical remission, defined as achieving ASDAS inactive or moderate disease (ASDAS score \<2.1) at weeks 24, were randomly assigned to receive either blinded 50mg Yisaipu (continuation arm), 25mg Yisaipu(reduction arm) or matching placebo (withdrawal arm) for 48 weeks during the double-blind period, for a total of 72 weeks of treatment. During the double-blind period, patients who experienced a flare (defined as an increase in BASDAI ≥2 points compare to the BASDAI score when randomization) were allocate to termination of this trial. ### Conditions Module **Conditions:** - Spondyloarthritis **Keywords:** - relapse - Yisaipu ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 150 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection, 50mg per week, Subcutaneous injection **Intervention Names:** - Drug: 50mg Yisaipu **Label:** 50mg etanercept **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injectio, 25mg per week, Subcutaneous injection **Intervention Names:** - Drug: 25mg etanercept **Label:** 25mg etanercept **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo, Subcutaneous injection per week **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 50mg etanercept **Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection, 50mg per week **Name:** 50mg Yisaipu **Other Names:** - 50mg entanercept(Yisaipu) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 25mg etanercept **Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection, 25mg per week **Name:** 25mg etanercept **Other Names:** - 25mg entanercept(Yisaipu) **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Placebo **Description:** The injection method and frequency of placebo is the same as the other arms. **Name:** Placebo **Other Names:** - placebo arm **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** proportion of patients achieving ASDAS<2.1 **Time Frame:** 72 week #### Secondary Outcomes **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** proportion of patients achieving ASDAS<1.3 **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** proportion of ASDAS major improvement **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** proportion of ASDAS clinically important improvement **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** ASAS 20 **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** ASAS 40 **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** ASAS5/6 **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** ASAS PR **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** BASDAI50 **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** BASDAI **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** BASFI **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** BASMI **Time Frame:** 72 weeks **Description:** The unabbreviated scale title is VAS from 0 to 100mm. 100 mm mean the most severe pain **Measure:** spinal pain score **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** patient global assessment(PGA) score **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** physician global assessment(PhGA) score **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** ESR **Time Frame:** 72 weeks **Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period **Measure:** CRP **Time Frame:** 72 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Fulfill the 2009 ASAS criteria for axial spondyloarthritis(SpA), and without bilateral more than grave 2 or unilateral more than grave 3 sacroilitis on X ray plan * Active disease phase of SpA, defined as BASDAI≥4 or ASDAS≥2.1 * Inadequate response to NSAID≥4 week * Application of NSAID with stable dose for no less than 2 weeks * Stable dose of prenisone for at least four weeks at ≤10mg per day if used at screening, or stop use for at least 4 weeks. * Stable dose of any DMARD for at least four weeks if used at screening, or stop use for at least 4 weeks * Stop and receiving washing out for at least 4 week if receiving Chinese traditional drug for AS, physical treatment, vaccication or IVIG. * The lab exam should achieve the criteria as below: Hb≥85g/L, 3.5×109/L≤WBC count≤10×109/L, PLT≥ lower limit of normal range, ALT≤2 fold of upper limit of normal range, serum creatine ≤upper limit of normal range. * Negative pregnacy test for female patients. And promise to carry out contraception during the trial and 6 weeks after the trial is ended. * Sign the informed consent. Exclusion criteria: * Previous application of any biologic agents. * Allergic to any element of Yisaipu® * Intolerance to NASID. * History of active tubercolosis, or radiographic evidence of present or previous history of pulmonary tubercolosis, or close contact with patients with tubercolosis, or with high risk of infection of tubercolosis such as immune suppression status, or strong positive of PPD skin test with diameter ≥10mm. * Presence of acute infection or acute onset of chronic infection at screen. * Invasive fungal infection or conditional infection within 6 months prior to screen. * Present or history of serious liver disease. * History of infection on artifitial joints. * Organ transplantation surgery within 6 months prior to screen. * Presence of other autoimmune diseases, including IBD, psoriasis, uveitis, SLE, multiple sclerosis, etc. * History of congestive heart failure. * History of malignancies within 5 years prior to screen, excluding complete resection of squamous cell carcinoma, or basal cell carcinoma or cervical carcinoma in situ. * AIDS or HIV infection. * History of lymphoma or lymphoproliferative disorders. * Presence of serious disorder of important organs or system. * Presence of factors which may influence the compliance. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Guangzhou **Country:** China **Facility:** Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University **State:** Guangdong **Zip:** 510060 #### Overall Officials **Official 1:** **Affiliation:** 3rd Affiliated Hospital of Sun Yat-sen University **Name:** Jieruo Gu, Professor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000001850 - Term: Bone Diseases, Infectious - ID: D000007239 - Term: Infections - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000013122 - Term: Spinal Diseases - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000025242 - Term: Spondylarthropathies - ID: D000000844 - Term: Ankylosis ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15961 - Name: Spondylitis - Relevance: HIGH - As Found: Spondyloarthritis - ID: M23035 - Name: Spondylarthritis - Relevance: HIGH - As Found: Spondyloarthritis - ID: M12284 - Name: Necrosis - Relevance: HIGH - As Found: Necrosis - ID: M2697 - Name: Axial Spondyloarthritis - Relevance: HIGH - As Found: Axial Spondyloarthritis - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5129 - Name: Bone Diseases, Infectious - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15919 - Name: Spinal Diseases - Relevance: LOW - As Found: Unknown - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M23036 - Name: Spondylarthropathies - Relevance: LOW - As Found: Unknown - ID: M4170 - Name: Ankylosis - Relevance: LOW - As Found: Unknown - ID: T5412 - Name: Spondylarthropathy - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013166 - Term: Spondylitis - ID: D000025241 - Term: Spondylarthritis - ID: D000089183 - Term: Axial Spondyloarthritis - ID: D000009336 - Term: Necrosis ### Intervention Browse Module - Ancestors - ID: D000000894 - Term: Anti-Inflammatory Agents, Non-Steroidal - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000018501 - Term: Antirheumatic Agents - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M311 - Name: Etanercept - Relevance: HIGH - As Found: Activation - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4218 - Name: Anti-Inflammatory Agents, Non-Steroidal - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068800 - Term: Etanercept ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00012779 **Brief Title:** Effectiveness of a Health Education Program in a Primary Care Setting **Official Title:** Effectiveness of a Health Education Program in a Primary Care Setting #### Organization Study ID Info **ID:** IIR 95-118 #### Organization **Class:** FED **Full Name:** VA Office of Research and Development ### Status Module #### Completion Date **Date:** 2003-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-04-07 **Type:** ESTIMATED **Last Update Submit Date:** 2015-04-06 **Overall Status:** COMPLETED **Status Verified Date:** 2005-06 #### Study First Post Date **Date:** 2001-03-16 **Type:** ESTIMATED **Study First Submit Date:** 2001-03-14 **Study First Submit QC Date:** 2001-03-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** US Department of Veterans Affairs #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study was designed to assess the effectiveness of a Health Education Program (HEP) for improving the well-being and reducing the health care use and cost of care of frail older outpatient veterans, and for improving the well-being of their spouse caregivers. HEP is a multi-component group program delivered in 8 weekly, 2-hour sessions, and 10 monthly 2-hour follow-up sessions, it includes emotion-focused and problem focused coping strategies, education and support. **Detailed Description:** Background: This study was designed to assess the effectiveness of a Health Education Program (HEP) for improving the well-being and reducing the health care use and cost of care of frail older outpatient veterans, and for improving the well-being of their spouse caregivers. HEP is a multi-component group program delivered in 8 weekly, 2-hour sessions, and 10 monthly 2-hour follow-up sessions, it includes emotion-focused and problem focused coping strategies, education and support. Objectives: The objectives of this study are to evaluate: 1) effects of HEP on the perceived health status, emotional well-being, and social support of frail veterans; 2) effects of HEP on the perceived health, emotional well-being, social support, burden levels, self-appraisal of change, pressing problems associated with caregiving, knowledge and use of community resources by caregiver; and 3) effects of HEP on the health care use and costs of care recipients. Methods: HEP was evaluated using a randomized control group design. The design has two levels of intervention, HEP vs. Usual Care (UC), 3 VA medical centers (VAMCs), and 4 times of measurement (at baseline, after the 8th HEP meeting, and at 1 and 2 years after baseline). Data reported here are for 8 week and 1-year psychosocial outcomes and 18 months for VA cost. Caregivers and veterans (n = 466) were randomized in 3 VAMCs, 114 to UC and 119 to HEP. The typical caregiver was 68 years old, married, white, female, with some college education and living with the veteran. The typical veteran care recipient was 74 years old, white, male with some college education, and suffered from one or more chronic health problems. Fifteen HEP groups were conducted. Caregivers and recipients were assessed on: 1) health and functional status; 2) emotional well-being; and 3) social support. In addition, caregivers were assessed for change in coping skills, change in burden level, pressing problems, and knowledge and use of community resources. Data was analyzed using random effects regression models. Status: Data on two-year outcomes for health and functional status, emotional well-being, and social support of caregivers and veterans, problems associated with caregiving and Medicare plus VA costs are being collected and analyzed for an amended final report. ### Conditions Module **Conditions:** - Frail Elderly **Keywords:** - Health Care Education - Health Care Cost ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 288 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: Health Education Program **Label:** Arm 1 **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm 1 **Name:** Health Education Program **Type:** BEHAVIORAL ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Caregiver inclusion criteria: 2) married to, and living with, the care recipient; 2) age 55 and older; 3) being the primary care provider for the care recipient and reporting at least a moderate level of burden on the Caregiver Strain Index; 4) report spouse has poor health care; and 5) receiver age 55 and suffering from chronic health condition. Exclusion Criteria: **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Brockton **Country:** United States **Facility:** VA Boston Healthcare System Brockton Campus, Brockton, MA **State:** Massachusetts **Zip:** 02301 **Location 2:** **City:** Albany **Country:** United States **Facility:** Albany VA Medical Center Samuel S. Stratton, Albany, NY **State:** New York **Zip:** 12208 **Location 3:** **City:** Buffalo **Country:** United States **Facility:** VA Western New York Healthcare System, Buffalo, NY **State:** New York **Zip:** 14215 #### Overall Officials **Official 1:** **Affiliation:** Albany VA Medical Center Samuel S. Stratton, Albany, NY **Name:** Joseph B. Engelhardt, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05103579 **Brief Title:** Design and Rationale of the Assessment of the MindMics Recording System **Official Title:** Design and Rationale of the Assessment of the Mindmics Recording System to Collect Data to Facilitate the Development of an Algorithm to Discriminate Atrial Fibrillation From Sinus Rhythm #### Organization Study ID Info **ID:** Pro00096535 #### Organization **Class:** INDUSTRY **Full Name:** MindMics Inc ### Status Module #### Completion Date **Date:** 2021-01-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-11-02 **Type:** ACTUAL **Last Update Submit Date:** 2021-11-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-31 **Type:** ACTUAL #### Start Date **Date:** 2020-03-24 **Type:** ACTUAL **Status Verified Date:** 2021-11 #### Study First Post Date **Date:** 2021-11-02 **Type:** ACTUAL **Study First Submit Date:** 2021-10-18 **Study First Submit QC Date:** 2021-11-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** MindMics Inc #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** MindMics earbuds is a new technology designed enhance an individual's quality of life by continuously monitoring the heart rate, stress, and blood pressure allowing patients to make decisions regarding their health. MindMics has a working prototype of the ear buds which will perform all the conventional tasks of earbuds (listen to music, etc.), but, in addition, will measure heart rate, stress, blood pressure. The earbuds capture the sounds made by the various cardiac structures pulsing and moving blood. The sound is caused by the acceleration and deceleration of blood and the turbulence developed during rapid blood flow. **Detailed Description:** Introduction: This study will evaluate the efficacy of the MindMics earbud recording apparatus to record data from patients with known atrial fibrillation as well as those in sinus rhythm. Patients in the clinic and patients with atrial fibrillation scheduled to undergo elective direct-current cardioversion will be the chosen subjects. This process will select a variety of patients to allow evaluation of the Mindmics apparatus's ability to collect data from patients with normal as well as abnormal cardiac rhythms. Hypotheses The MindMics earbud device is capable of recording normal cardiac rhythms in patients noninvasively using earbud device in a noninvasive manner. The same apparatus may be capable of discerning atrial fibrillation compared with normal sinus rhythm. This will be evaluated by collecting information from patients with atrial fibrillation in the office as well as those scheduled to undergo an elective direct-current cardioversion procedure. A timed recording of the clinical rhythm while wearing the apparatus will allow simultaneous recording of data from an ECG recording (documenting the patient's clinical arrhythmia) at the same time the MindMics earbud records its data obtained during the ECG recording of the patient's rhythm. For those patient scheduled for direct current cardioversion, the patient will undergo the direct-current cardioversion and a second recording will be obtained during sinus rhythm afterwards allowing an appropriate comparison of the differences in the recording sets. The objective is to demonstrate differences between recordings made in atrial fibrillation and those in sinus rhythm that can be used to develop an algorithm allow discernment between atrial fibrillation and sinus rhythm. OVERALL DESIGN This study is designed to collect sequential patient's in a nonrandomized unblinded procedure designed to collect information using the apparatus to document its capability of recording cardiac rhythm data, then using this recorded data to determine whether the patient has an abnormal cardiac rhythm. Initial efforts will be directed to develop an algorithm to detect atrial fibrillation. Patients will be recruited from inpatients at Palmetto Tuomey Medical center or in the outpatient office during routine office visits for patients with clinical arrhythmias for elective recording for group 1. Group 2 patients will be recruited prior to direct-current cardioversion. Both groups will be explained the study, what is their participation, potential risk and expectations for their participation in the study. Once selected each patient will be required to sign a study protocol consent form before actual entry into the study. Once the consent is completed, the patients will be connected to the Mindmics apparatus as well as an electrocardiographic recording system. The study participant will lie quietly collecting simultaneous electrocardiographic data and data from the Mindmics earbuds. Group 1 patients will be identified as outpatients during their routine office visits will have 15 minutes of recording in a patient examination room during the office visit. Group 2 patients undergoing Direct-Current Cardioversion will have 15 minutes of recording prior to the cardioversion procedure and 15 minutes of recording after completion of the cardioversion procedure. NUMBER OF PARTICIPANTS Approximately 25 patients will be recruited for group 1 from inpatient or outpatient office visits. These patients will have persistent atrial fibrillation during the office visit. If necessary would consider increasing the total number of patients to 50 in this group Approximately 25 patients will be recruited for group 2 prior to direct-current cardioversion allowing collection of data from before and after cardioversion to document differences in recordings during sinus rhythm after having successful cardioversion from atrial fibrillation. While certainly some patients will revert back to atrial fibrillation and not have periods of sinus rhythm is anticipated the vast majority of patients will have successful cardioversions long enough to record at least the 15 minutes post cardioversion in sinus rhythm. If necessary would consider increasing the total number of patients to 50 in this group DURATION The total duration of involvement for each study participant is for the duration of the recording interval. Group 1 participants will have a 15-minute recording interval while those in group to will have 2 sessions of 15 minutes each separated by the direct current cardioversion. No further participation will be required. All data collected during the study will be kept by Mindmics. All data collected in the study will be de-identified OUTCOME MEASURES and STATISTICAL ANALYSIS Each recording will be evaluated by Mindmics to evaluate the ability of the recording apparatus to provide data that would lead to clear discernment of the patient's cardiac rhythm as well as rate related phenomena. At this juncture, it is anticipated the collected data will be used to develop and test algorithms yet to be developed and to make clinical determinations of the cardiac rhythms. Initial data will be evaluated to determine if the Mindmics earbuds are capable of discriminating atrial fibrillation from normal sinus rhythm. For that reason, it is not possible to suggest a statistical method until it is determined the device data can be used to evaluate differences in cardiac rhythm. SAFETY There is no potential harm or injury associated with the research. The probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. There are no potential risks with respect to psychological, sociological, economic, or legal. The overall risk of the device in minimum. Potential Benefit to Participants This study is performed in such a manner that it is not anticipated there would be an ability to provide diagnostic data that may be helpful for the study participants. ### Conditions Module **Conditions:** - Atrial Fibrillation - Arrythmia ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 29 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with AFib **Intervention Names:** - Device: MindMics **Label:** Patients with AFib #### Arm Group 2 **Description:** Normal patients without AFib **Intervention Names:** - Device: MindMics **Label:** Normal patients ### Interventions #### Intervention 1 **Arm Group Labels:** - Normal patients - Patients with AFib **Description:** Patients rhythms was recorded using MindMics device **Name:** MindMics **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Sensitivity and specificity for detecting Atrial Fibrillation using inter-beat intervals and statistical measures based on inter-beat intervals **Measure:** Performance of the MindMics device for detecting Atrial Fibrillation based on inter-beat intervals **Time Frame:** 30 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * AFib Exclusion Criteria: * N/A **Healthy Volunteers:** True **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Approximately 25 patients will be recruited for group 1 from inpatient or outpatient office visits. Approximately 25 patients will be recruited for group 2 prior to direct-current cardioversion allowing collection of data from before and after cardioversion to document differences in recordings during sinus rhythm after having successful cardioversion from atrial fibrillation. ### Contacts Locations Module #### Locations **Location 1:** **City:** Sumter **Country:** United States **Facility:** Prisma Health **State:** South Carolina **Zip:** 29150 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Atrial Fibrillation - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04961879 **Brief Title:** Dorsal Finger Reconstruction **Official Title:** Comparative Study to Evaluate the Difference Between Reversed Cross Finger Flap Versus Reversed Island Homo-digital Flap in Distal Dorsal Finger Defect Reconstruction #### Organization Study ID Info **ID:** Soh-Med-21-07-09 #### Organization **Class:** OTHER **Full Name:** Sohag University ### Status Module #### Completion Date **Date:** 2022-03 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2022-02-17 **Type:** ACTUAL **Last Update Submit Date:** 2022-02-16 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-02 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-14 **Type:** ACTUAL **Status Verified Date:** 2022-02 #### Study First Post Date **Date:** 2021-07-14 **Type:** ACTUAL **Study First Submit Date:** 2021-07-13 **Study First Submit QC Date:** 2021-07-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sohag University #### Responsible Party **Investigator Affiliation:** Sohag University **Investigator Full Name:** Elhossieny abdelaal mohamed **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** objective of this study is To compare reversed cross finger flap with reversed island homo-digital flap in distal dorsal finger defect reconstruction regarding reliability \& functional and aesthetic outcomes . comparative study that will be conducted at Plastic surgery department, Sohag university hospital on 30 patients .The population of the study will be patients with distal dorsal digital defects. We will divide the cases into two equal groups: the first are operated with reversed cross-finger flap and the second are operated with reversed island homo-digital flap. ### Conditions Module **Conditions:** - Finger Injuries ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: Reversed Cross Finger Flap **Label:** Reversed Cross Finger Flap group 1 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Procedure: reversed island homo-digital flap **Label:** Reversed island Homo-digital Flap group 2 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Reversed Cross Finger Flap group 1 **Description:** distal dorsal finger defect will be reconstructed by reversed cross finger flap - reversed cross finger flap is a modified cross finger flap harvested from an adjacent finger . **Name:** Reversed Cross Finger Flap **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Reversed island Homo-digital Flap group 2 **Description:** distal dorsal finger defect will be reconstructed by reversed island homo-digital flap - this flap is harvested from the same finger . **Name:** reversed island homo-digital flap **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** difference in range of motion between group 1 and group 2 will be measured by manual goniometer in degrees **Measure:** difference in range of motion between group 1 and group 2 **Time Frame:** difference in range of motion between group 1 and group 2 will be measured at 4 months postoperative ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * patients with dorsal digital defect distal to distal interphalangeal joint (DIP) joint * defect size ranged from 1 to 2 cm in width and 1-3 cm in length Exclusion Criteria: * chronic heavy smokers, * traumatic injury to the donor site and perforator . **Maximum Age:** 70 Years **Minimum Age:** 5 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Sohag **Country:** Egypt **Facility:** Sohag University **Zip:** 82525 ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2022-03-09 - Date Unknown: Unknown #### Event: RESET - Date: 2022-06-06 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006230 - Term: Hand Injuries - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M8513 - Name: Finger Injuries - Relevance: HIGH - As Found: Finger Injuries - ID: M9322 - Name: Hand Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005383 - Term: Finger Injuries ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2022-03-09 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2022-03-09 - Reset Date: 2022-06-06 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03806179 **Acronym:** LYMRIT-37-07 **Brief Title:** Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL **Official Title:** A Phase 1b Open-label Study of Betalutin in Combination With Rituximab in Patients With Relapsed/Refractory Follicular Lymphoma (Archer-1) #### Organization Study ID Info **ID:** LYMRIT -37-07(Archer-1) #### Organization **Class:** INDUSTRY **Full Name:** Nordic Nanovector #### Secondary ID Infos **Domain:** EudraCT **ID:** 2017-004506-18 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2022-08-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-22 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-08-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-12-22 **Type:** ACTUAL **Results First Submit Date:** 2023-01-15 **Results First Submit QC Date:** 2023-12-21 #### Start Date **Date:** 2018-10-04 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2019-01-16 **Type:** ACTUAL **Study First Submit Date:** 2019-01-14 **Study First Submit QC Date:** 2019-01-15 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** ICON Clinical Research #### Lead Sponsor **Class:** INDUSTRY **Name:** Nordic Nanovector #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is a Phase 1b, open-label, single arm dose escalation study of Betalutin followed by rituximab in patients with previously treated follicular lymphoma. The purpose of this study is to characterise the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of Betalutin in combination with rituximab. ### Conditions Module **Conditions:** - Non Hodgkin Lymphoma - Follicular Lymphoma - Relapsed Follicular Lymphoma **Keywords:** - Radioimmunotherapy - Lu-177 - Betalutin - Phase 1b - Combination - Rituximab ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 7 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years **Intervention Names:** - Drug: 10 MBq/kg Betalutin **Label:** 10 MBq/kg Betalutin with rituximab treatment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years **Intervention Names:** - Drug: 15 MBq/kg Betalutin **Label:** 15 MBq/kg Betalutin with rituximab treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 10 MBq/kg Betalutin with rituximab treatment **Description:** 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **Name:** 10 MBq/kg Betalutin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 15 MBq/kg Betalutin with rituximab treatment **Description:** 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **Name:** 15 MBq/kg Betalutin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03) in the first 12 weeks after Betalutin **Measure:** Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** Best overall response of combination treatment using tumour responses based on CT and PET/CT imaging (classified as as complete response, partial response, no response/stable disease or progressive disease as described in "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification") **Measure:** Preliminary Anti-tumour Activity **Time Frame:** 25 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient must be ≥18 years at the time of signing the informed consent * ECOG performance status of 0-2 * Histologically confirmed diagnosis (by 2008 World Health Organization \[WHO\] classification) of follicular lymphoma (grade 1, 2 or 3a) * At least one (but not more than 3) prior regimens with an anti-CD20 antibody (alone or in combination with chemotherapy), with documented relapsed, refractory disease (must not be anti-CD20 antibody-refractory) or PD * Presence of at least one bi-dimensionally measurable lesion by CT or MRI: longest diameter (LDi) \>1.5 cm for a nodal lesion; LDi \>1.0 cm for an extranodal lesion within 28 days prior to start of treatment * Normal organ and bone marrow function defined as: 1. Absolute neutrophil count ≥1.5 x 109/L; 2. Platelet count ≥150 x 109/L; 3. Haemoglobin ≥9 g/dL; 4. Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert's syndrome \[\<3.0 mg/dL\]); 5. Aspartate transaminase (AST); Alanine transaminase (ALT) or Alkaline phosphatase (ALP) ≤2.5 x ULN (or ≤5.0 x ULN if liver involvement by primary disease); 6. Adequate renal function as demonstrated by a serum creatinine within the upper limit of normal range * Bone marrow involvement by lymphoma \<25% * Life expectancy \>3 months * Negative hepatitis B, hepatitis C and human immunodeficiency virus (HIV) screening tests * Patients must agree to use effective contraception for 12 months following last study drug administration Exclusion criteria: * Previous haematopoietic stem cell transplantation (autologous and allogenic) * Evidence of histological transformation from FL to DLBCL at time of screening. * Previous total body irradiation * Chemotherapy, immunotherapy or investigational therapy within 28 days before the start of study drug administration (corticosteroid treatment at doses of ≤20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor \[GM CSF\] are permitted up to 2 weeks prior to start of study treatment) or failure to recover from AEs associated with prior treatment * Previous treatment with radioimmunotherapy * Patients who are receiving any other investigational medicinal products * Known or suspected central nervous system (CNS) involvement of lymphoma * History of a previous treated cancer except for the following: 1. adequately treated local basal cell or squamous cell carcinoma of the skin 2. cervical carcinoma in situ 3. superficial bladder cancer or localised prostate cancer undergoing surveillance or surgery 4. localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy 5. other adequately treated Stage 1 or 2 cancer currently in CR * Pregnant or lactating women * Exposure to another CD37 targeting drug * A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any excipient used in RTX, lilotomab or Betalutin * Receipt of live, attenuated vaccine within 30 days prior to enrolment * Evidence of severe or uncontrolled systemic diseases (e.g. ongoing infection, respiratory, cardiac, hepatic or psychiatric conditions) which in the Investigator's opinion would compromise the protocol objectives **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ostrava- **Country:** Czechia **Facility:** Klinika Hematoonkologie **State:** Porubá **Zip:** 807-52 **Location 2:** **City:** Oslo **Country:** Norway **Facility:** Oslo University Hospital **Zip:** N-0310 #### Overall Officials **Official 1:** **Affiliation:** Oslo University Hospital **Name:** Alexander Fosså, MD.PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Repetto-Llamazares AHV, Malenge MM, O'Shea A, Eiriksdottir B, Stokke T, Larsen RH, Dahle J. Combination of 177 Lu-lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non-Hodgkin's lymphoma. Eur J Haematol. 2018 Oct;101(4):522-531. doi: 10.1111/ejh.13139. Epub 2018 Aug 31. **PMID:** 29993152 **Citation:** Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800. **PMID:** 25113753 #### See Also Links **Label:** Sponsor home page **URL:** http://www.nordicnanovector.com ## Document Section ### Large Document Module #### Large Docs - Date: 2021-10-04 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 13078903 - Type Abbrev: Prot_SAP - Upload Date: 2023-12-11T08:23 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000008228 - Term: Lymphoma, Non-Hodgkin ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: HIGH - As Found: Lymphoma - ID: M11221 - Name: Lymphoma, Follicular - Relevance: HIGH - As Found: Follicular lymphoma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M11222 - Name: Lymphoma, Non-Hodgkin - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma - ID: T2361 - Name: Follicular Lymphoma - Relevance: HIGH - As Found: Follicular lymphoma ### Condition Browse Module - Meshes - ID: D000008223 - Term: Lymphoma - ID: D000008224 - Term: Lymphoma, Follicular ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M373 - Name: Rituximab - Relevance: LOW - As Found: Unknown ### Misc Info Module #### Removed Countries - Country: Poland - Country: United Kingdom - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Treatment emergent AEs from the first dose of rituximab are presented. Under protocol Versions 1 to 3, it was planned to collect treatment-related AEs for the duration of the follow-up period, up to 5 years. This period was removed under protocol Version 4; only the first two participants had entered the follow-up period at the time this version was approved, therefore only these two participants had treatment-related AEs collected up to 36 months before follow-up was closed. #### Event Groups **Group ID:** EG000 **Title:** 10 MBq/kg Betalutin With Rituximab Treatment **Deaths Num At Risk:** 4 **Description:** 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 10 MBq/kg Betalutin: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** EG000 **Other Num Affected:** 4 **Other Num at Risk:** 4 **Serious Number Affected:** 3 **Serious Number At Risk:** 4 **Title:** 10 MBq/kg Betalutin With Rituximab Treatment **Group ID:** EG001 **Title:** 15 MBq/kg Betalutin With Rituximab Treatment **Deaths Num At Risk:** 3 **Description:** 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 15 MBq/kg Betalutin: 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** EG001 **Other Num Affected:** 3 **Other Num at Risk:** 3 **Serious Number At Risk:** 3 **Title:** 15 MBq/kg Betalutin With Rituximab Treatment **Frequency Threshold:** 0 #### Other Events **Term:** Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Leukopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Facial pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Influenza-like illness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Erysipelas **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Rash pustular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (Unspecified) **Term:** Gamma-glutamyltransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Muscle spasm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Restless leg syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Night sweats **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Rash erythematous **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Primary progressive aphasia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Nerve degeneration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Axillary pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Hyperhidrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Swelling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Weight decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Post-traumatic headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Concussion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (Unspecified) **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Wound **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (Unspecified) **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Skin infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (Unspecified) **Term:** Hypoaesthesia oral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) #### Serious Events **Term:** Erysipelas **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Occurred \>92 days (12 weeks) after Betalutin injection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (Unspecified) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 4 **Group ID:** EG001 **Num At Risk:** 3 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Occurred \>92 days (12 weeks) after Betalutin injection **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (Unspecified) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 4 **Group ID:** EG001 **Num At Risk:** 3 **Term:** Bronchitis viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Occurred \>92 days (12 weeks) after Betalutin injection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (Unspecified) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 4 **Group ID:** EG001 **Num At Risk:** 3 **Time Frame:** All adverse events (AEs) were collected from the time of informed consent until 4 weeks after the last rituximab dose, up to 25 months. Thereafter treatment related AEs were collected up to 36 months for the first two participants only. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 4 **Group ID:** BG001 **Value:** 3 **Group ID:** BG002 **Value:** 7 **Units:** Participants ### Group **ID:** BG000 **Title:** 10 MBq/kg Betalutin With Rituximab Treatment **Description:** 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 10 MBq/kg Betalutin: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 ### Group **ID:** BG001 **Title:** 15 MBq/kg Betalutin With Rituximab Treatment **Description:** 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 15 MBq/kg Betalutin: 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 7 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 6 **Class Title:** Norway #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Class Title:** Czechia **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Limitations and Caveats **Description:** Whilst the protocol makes reference to a separate statistical analysis plan, given that only seven participants were enrolled and the originally planned expansion phase in a further 20-25 participants was not performed (removed under protocol Version 4.0) a separate detailed statistical analysis plan was not generated. ### Point of Contact **Email:** mail@nordicnanovector.com **Organization:** Nordic Nanovector **Phone:** +47 22 18 33 01 **Title:** Head of Clinical Operations ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** Complete response ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** Partial response ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03) in the first 12 weeks after Betalutin **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 12 weeks **Title:** Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03) **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 10 MBq/kg Betalutin: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** OG000 **Title:** 10 MBq/kg Betalutin With Rituximab Treatment ##### Group **Description:** 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 15 MBq/kg Betalutin: 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** OG001 **Title:** 15 MBq/kg Betalutin With Rituximab Treatment #### Outcome Measure 2 **Description:** Best overall response of combination treatment using tumour responses based on CT and PET/CT imaging (classified as as complete response, partial response, no response/stable disease or progressive disease as described in "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification") **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 25 months **Title:** Preliminary Anti-tumour Activity **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 10 MBq/kg Betalutin: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** OG000 **Title:** 10 MBq/kg Betalutin With Rituximab Treatment ##### Group **Description:** 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 15 MBq/kg Betalutin: 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** OG001 **Title:** 15 MBq/kg Betalutin With Rituximab Treatment ### Participant Flow Module #### Group **Description:** 10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 10 MBq/kg Betalutin: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** FG000 **Title:** 10 MBq/kg Betalutin With Rituximab Treatment #### Group **Description:** 15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years 15 MBq/kg Betalutin: 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2 **ID:** FG001 **Title:** 15 MBq/kg Betalutin With Rituximab Treatment #### Period **Title:** Overall Study ##### Withdraw **Type:** Progressive disease ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04075279 **Brief Title:** Heart at Work Study **Official Title:** Cardiovascular Mechanisms of the Occupational Physical Activity Health Paradox: 24-hour Physical Activity, Blood Pressure, and Heart Rate #### Organization Study ID Info **ID:** STUDY19050097 #### Organization **Class:** OTHER **Full Name:** University of Pittsburgh ### Status Module #### Completion Date **Date:** 2020-07-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-05-03 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-04-20 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-05-03 **Type:** ACTUAL **Results First Submit Date:** 2021-04-06 **Results First Submit QC Date:** 2021-04-06 #### Start Date **Date:** 2019-10-17 **Type:** ACTUAL **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2019-08-30 **Type:** ACTUAL **Study First Submit Date:** 2019-08-28 **Study First Submit QC Date:** 2019-08-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Pittsburgh #### Responsible Party **Investigator Affiliation:** University of Pittsburgh **Investigator Full Name:** Tyler Quinn **Investigator Title:** Principle Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an observational study to examine the cardiovascular mechanisms of increased cardiovascular mortality in those with high activity occupations. **Detailed Description:** The current proposal uses a repeated-measures, within-subject design to address our aims. Twenty male participants will report to the laboratory to provide informed consent, complete baseline assessments, and receive ambulatory monitors. Following this session, each participant will wear physical activity and ambulatory cardiovascular monitors for 7 days, including at least one non-work day and one work day. Characterization of work activity will use physical activity data from self-reported time at work (Specific Aim I). The 24-hour cardiovascular load (HR and BP) and nocturnal HRV will be compared across work and non-work days (Specific Aim II). Lastly, whether fitness level or job strain modify the difference in cardiovascular strain between work vs. non-work days will be evaluated (Specific Aim III). ### Conditions Module **Conditions:** - Occupational Diseases - Cardiovascular Diseases - Cardiovascular Risk Factor - Occupational Exposure ### Design Module #### Design Info **Observational Model:** CASE_CROSSOVER **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 19 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** We will calculate the average heart rate over each 24 hour period throughout a one week monitoring period. **Measure:** 24-hour Heart Rate **Time Frame:** 24 hours #### Secondary Outcomes **Description:** We will calculate the average systolic blood pressure over a 24-hour period on two separate days (workdays versus non-workdays). **Measure:** 24-hour Ambulatory Systolic Blood Pressure **Time Frame:** 24 hours **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is root mean square successive differences (RMSSD). **Measure:** Nocturnal Heart Rate Variability, RMSSD **Time Frame:** approximately 8 hours (sleep time) **Description:** This physical activity metric of steps per day was calculated as average number of steps during each day type (work versus non-workdays) throughout one week **Measure:** Physical Activity Pattern. Steps Per Day **Time Frame:** 1 week **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is standard deviation of the normal to normal RR intervals (SDNN). **Measure:** Nocturnal Heart Rate Variability, SDNN **Time Frame:** approximately 8 hours (sleep time) **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is low frequency power (LF). **Measure:** Nocturnal Heart Rate Variability, LF **Time Frame:** approximately 8 hours (sleep time) **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is high frequency power (HF). **Measure:** Nocturnal Heart Rate Variability, HF **Time Frame:** approximately 8 hours (sleep time) **Description:** This physical activity metric of minutes of moderate to vigorous physical activity was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Measure:** Physical Activity Pattern. MVPA **Time Frame:** 1 week **Description:** This physical activity metric of minutes of light physical activity was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Measure:** Physical Activity Pattern. LPA **Time Frame:** 1 week **Description:** This physical activity metric of minutes of sedentary time was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Measure:** Physical Activity Pattern. Sedentary **Time Frame:** 1 week **Description:** This physical activity metric of minutes of upright time was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Measure:** Physical Activity Pattern. Upright **Time Frame:** 1 week **Description:** We will calculate the average diastolic blood pressure over a 24-hour period on two separate days (workdays versus non-workdays). **Measure:** 24-hour Ambulatory Diastolic Blood Pressure **Time Frame:** 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * middle age (35-59 years) * male * self-report working full-time in the food service industry (≥30 hours/week) * self-report predominantly completing light intensity activity job responsibilities (≥75% work time walking, light movement, or standing) Exclusion Criteria: * Resting blood pressure of ≥150 mmHg systolic and/or ≥95 mmHg diastolic * currently taking medications that are known to affect blood pressure or heart rate (e.g. Beta-blockers, ACE inhibitors, etc.) * greater than low risk to participate in physical activity as determined by PAR-Q (answer of yes to any of the 7 physical activity readiness questionnaire questions) * report working a second job in addition to their primary full-time job * report working overnight shifts (10pm-6am) * reported physical dysfunction (inability to walk 2 city blocks or climb 2 flights of stairs) * inability to complete the sub-maximal exercise test to completion (80% age-predicted heart rate maximum) * Currently being treated for a serious medical condition such as kidney disease, liver disease, cancer, or heart disease. **Gender Based:** True **Gender Description:** Only males are eligible for this study. **Maximum Age:** 59 Years **Minimum Age:** 35 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** MALE **Standard Ages:** - ADULT **Study Population:** Middle-aged male food service workers ### Contacts Locations Module #### Locations **Location 1:** **City:** Pittsburgh **Country:** United States **Facility:** Physical Activity and Weight Management Research Laboratory **State:** Pennsylvania **Zip:** 15261 #### Overall Officials **Official 1:** **Affiliation:** Graduate Student **Name:** Tyler D Quinn, MS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Upon completion of all data collection, data will be analyzed and summary conclusions will be published in a peer reviewed scientific journal. **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2019-09-26 - Filename: Prot_SAP_ICF_000.pdf - Has ICF: True - Has Protocol: True - Has SAP: True - Label: Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Size: 21377333 - Type Abbrev: Prot_SAP_ICF - Upload Date: 2021-04-06T08:09 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC24 - Name: Occupational Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12719 - Name: Occupational Diseases - Relevance: HIGH - As Found: Occupational Diseases ### Condition Browse Module - Meshes - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000009784 - Term: Occupational Diseases ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Research Study Participation **Deaths Num At Risk:** 19 **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** EG000 **Other Num at Risk:** 19 **Serious Number At Risk:** 19 **Title:** Research Study Participation **Frequency Threshold:** 0 **Time Frame:** 1 week ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 19 **Units:** Participants ### Group **ID:** BG000 **Title:** Research Study Participation **Description:** Participants who were enrolled in the study and completed all study procedures. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 7.9 **Value:** 46.6 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 19 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 4 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 13 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 19 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 **Category Title:** Food Service #### Measurement **Group ID:** BG000 **Value:** 9 **Category Title:** Material Moving #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Healthcare #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Building and Grounds Maintenance **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Occupational Industry **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** yhh7@cdc.gov **Organization:** Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health **Phone:** 412-386-4450 **Title:** Dr. Tyler Quinn ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2 - **Upper Limit:** - **Value:** 83.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.4 - **Upper Limit:** - **Value:** 78.5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.7 - **Upper Limit:** - **Value:** 126.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8 - **Upper Limit:** - **Value:** 124.0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.04 - **Upper Limit:** - **Value:** 34.17 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.32 - **Upper Limit:** - **Value:** 35.34 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 945 - **Upper Limit:** - **Value:** 12,772 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1,063 - **Upper Limit:** - **Value:** 7,923 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.48 - **Upper Limit:** - **Value:** 39.85 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.71 - **Upper Limit:** - **Value:** 42.14 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** 6.18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** 6.45 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.30 - **Upper Limit:** - **Value:** 5.22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.31 - **Upper Limit:** - **Value:** 5.56 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.2 - **Upper Limit:** - **Value:** 72.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.9 - **Upper Limit:** - **Value:** 41.5 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 19.9 - **Upper Limit:** - **Value:** 391.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.3 - **Upper Limit:** - **Value:** 285.2 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.4 - **Upper Limit:** - **Value:** 492.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22.5 - **Upper Limit:** - **Value:** 629.7 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.4 - **Upper Limit:** - **Value:** 462.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22.5 - **Upper Limit:** - **Value:** 325.2 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.0 - **Upper Limit:** - **Value:** 75.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.1 - **Upper Limit:** - **Value:** 72.6 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** We will calculate the average heart rate over each 24 hour period throughout a one week monitoring period. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** 24-hour Heart Rate **Type:** PRIMARY **Unit of Measure:** beats per minute ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 2 **Description:** We will calculate the average systolic blood pressure over a 24-hour period on two separate days (workdays versus non-workdays). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** 24-hour Ambulatory Systolic Blood Pressure **Type:** SECONDARY **Unit of Measure:** millimeters of Mercury ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 3 **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is root mean square successive differences (RMSSD). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** approximately 8 hours (sleep time) **Title:** Nocturnal Heart Rate Variability, RMSSD **Type:** SECONDARY **Unit of Measure:** milliseconds ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 4 **Description:** This physical activity metric of steps per day was calculated as average number of steps during each day type (work versus non-workdays) throughout one week **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 1 week **Title:** Physical Activity Pattern. Steps Per Day **Type:** SECONDARY **Unit of Measure:** steps per day ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 5 **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is standard deviation of the normal to normal RR intervals (SDNN). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** approximately 8 hours (sleep time) **Title:** Nocturnal Heart Rate Variability, SDNN **Type:** SECONDARY **Unit of Measure:** milliseconds ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 6 **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is low frequency power (LF). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** approximately 8 hours (sleep time) **Title:** Nocturnal Heart Rate Variability, LF **Type:** SECONDARY **Unit of Measure:** log milliseconds ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 7 **Description:** We will calculate the average heart rate variability during each night's sleep for a total of one week. The specific HRV variable presented is high frequency power (HF). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** approximately 8 hours (sleep time) **Title:** Nocturnal Heart Rate Variability, HF **Type:** SECONDARY **Unit of Measure:** log milliseconds ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 8 **Description:** This physical activity metric of minutes of moderate to vigorous physical activity was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 1 week **Title:** Physical Activity Pattern. MVPA **Type:** SECONDARY **Unit of Measure:** minutes per day ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 9 **Description:** This physical activity metric of minutes of light physical activity was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 1 week **Title:** Physical Activity Pattern. LPA **Type:** SECONDARY **Unit of Measure:** minutes per day ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 10 **Description:** This physical activity metric of minutes of sedentary time was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 1 week **Title:** Physical Activity Pattern. Sedentary **Type:** SECONDARY **Unit of Measure:** minutes per day ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 11 **Description:** This physical activity metric of minutes of upright time was calculated as average minutes during each day type (work versus non-workdays) throughout one week **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 1 week **Title:** Physical Activity Pattern. Upright **Type:** SECONDARY **Unit of Measure:** minutes per day ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation #### Outcome Measure 12 **Description:** We will calculate the average diastolic blood pressure over a 24-hour period on two separate days (workdays versus non-workdays). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** 24-hour Ambulatory Diastolic Blood Pressure **Type:** SECONDARY **Unit of Measure:** millimeters of Mercury ##### Group **Description:** Participants who were enrolled in the study and completed all study procedures. **ID:** OG000 **Title:** Research Study Participation ### Participant Flow Module #### Group **Description:** All participants were enrolled into a single arm and all comparisons were made within subjects. **ID:** FG000 **Title:** Middle-aged Males in High Activity Occupations #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 19 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 19 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04983979 **Acronym:** ORTIZ **Brief Title:** The ORTIZ Study: Optimising RASi Therapy With SZC **Official Title:** A Multi Site, Placebo Controlled, Double Blind Randomised Clinical Trial Evaluating the Effectiveness of Sodium Zirconium Cyclosilicate Versus Placebo to Enable Safe Optimisation of RASi Therapy in Patients With Diabetic Kidney Disease. #### Organization Study ID Info **ID:** 136721 #### Organization **Class:** OTHER **Full Name:** Barts & The London NHS Trust ### Status Module #### Completion Date **Date:** 2023-05-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-16 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-15 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2023-03-16 **Type:** ACTUAL #### Start Date **Date:** 2022-06-17 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2021-07-30 **Type:** ACTUAL **Study First Submit Date:** 2021-07-09 **Study First Submit QC Date:** 2021-07-21 **Why Stopped:** Lack of recruitment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Barts & The London NHS Trust #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The hypothesis is that 3 months' treatment with SZC versus placebo will enable RASi (Irbesartan) maximisation in a cohort of patients with diabetic kidney disease. **Detailed Description:** Inhibiting the renin angiotensin (RAS) system has been the cornerstone of therapy for patients with proteinuric CKD for almost 2 decades, to slow the decline in renal function, delay the presence of dialysis and reduce cardiovascular events and death. There is evidence in both the cardiac and renal literature that suggests that maximising the dose of RAS therapy leads to improved outcomes over smaller doses of RAS therapy. Indeed, many of the studies on which we base our care use doses which are higher than what the majority of our patients are taking. Thus patients are being systemically undertreated by therapies which have been shown to have robust reno protection. With up to 80% of patients on RASi therapy are not on maximal RASi therapy , putting them at risk of a more rapid progression and poorer outcomes and increased healthcare costs. An important reason for this is the presence or fear around hyperkalaemia. With reports of significantly increased rate of hyperkalaemia seen following increases in prescribing of RASi therapy. These concerns have lead NICE to recommend not starting patients on RASi therapy if their potassium is \>5mmol/l, and KDOQI guidelines recommending consideration of stopping RASi therapy if serum potassium is \>5.5mmol/l. ACE inhibitors and angiotensin receptor blockers are thought to confer long term renal protection through reduction of proteinuria. The reduction in glomerular pressure is a major mechanism leading to a reduction in proteinuria, and hence renal protection, however as a consequence there will also an acute fall in eGFR. Therefore, when starting/up titrating ACEi/ARB it is expected that there will be an acute fall in eGFR, which is expected to be more than compensated for due to the subsequent long term renal protection. Indeed, current NICE guidelines do not suggest any alteration in management until the drop in eGFR is \>25%. There is a currently huge unmet need to optimise RASi therapy in those patients with hyperkalaemia. There have been recent advances in novel therapeutics which can lower potassium in patients. One such agent is Sodium zirconium cyclosilicate (SZC). SZC is a highly selective inorganic cation exchanger designed to entrap potassium in the intestine. It has been shown to effective in lowering potassium in patients with heart failure, Diabetes, CKD and RASi therapy. With around a 1mmol/l fall in the serum potassium on those treated with SZC, compared to placebo. In the 5-large clinical trials it appears efficacious, well tolerated and safe. ### Conditions Module **Conditions:** - CKD - Diabetes Mellitus, Type 2 - Hyperkalemia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A Multi site, placebo controlled, double blind randomised clinical trial. ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** double blind randomised clinical trial. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 10 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 3 month treatment using Sodium zirconium cyclocilicate. Doses of 5 or 10g once daily will be used. The dose will be titrated according to potassium levels performed at clinic visits **Intervention Names:** - Drug: Sodium Zirconium Cyclosilicate **Label:** SZC **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 3 month treatment using matched placebo. Doses of 5 or 10g once daily will be used. The dose will be titrated according to potassium levels performed at clinic visits **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - SZC **Description:** sachets of 5g or 10g given OD titrated to serum potassium **Name:** Sodium Zirconium Cyclosilicate **Other Names:** - Lokelma **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** matched placebo given titrated according to potassium at a dose to 5 or 10g **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Proportion of patients on Maximum dose (300mg) Irbesartan therapy at 12 weeks compared to placebo **Measure:** Proportion of patients on Maximum dose (300mg) Irbesartan therapy at 12 weeks compared to placebo **Time Frame:** week 12 #### Secondary Outcomes **Description:** Change in potassium from baseline at each study visit (week 1, week 2, 4,6,8,12) **Measure:** Change in potassium from baseline at each time point **Time Frame:** at each study visit (week 1, week 2, 4,6,8,12) **Description:** Safety **Measure:** Frequency of adverse events **Time Frame:** assessed at each study visit (week 1, week 2, 4,6,8,12) **Description:** Proportion of patients who have a potassium of \>6mmol/l,, or \>6.5mmol/l at any time during the study **Measure:** Proportion of patients who have a potassium of >6mmol/l, or >6.5mmol/l at any time during the study • **Time Frame:** Assessed at each study visit (week 1, week 2, 4,6,8,12) **Description:** Proportion of patients who have a potassium of \<3.5mmol/l, assessed at each study visit (week 1, week 2, 4,6,8,12) **Measure:** Proportion of patients who have a potassium of <3.5mmol/l • **Time Frame:** Assessed at each study visit (week 1, week 2, 4,6,8,12) **Description:** Proportion of patients whose GFR falls by \>30% from the previous visit **Measure:** Proportion of patients whose Glomerular filtration rate (GFR) falls by >30% from the previous visit • **Time Frame:** Change in potassium from one visit to the next. Assessed at each study visit (week 1, week 2, 4,6,8,12) **Description:** Change in GFR at the end of study from baseline **Measure:** Change in GFR at the end of study from baseline **Time Frame:** Between baseline and week 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Able and willing to provide written informed consent 2. Adults ≥ 18years old 3. Type 2 Diabetes 4. CKD defined as eGFR 25-60ml/min 5. Albuminuria with uACR measured at \>33.9.mg/mmol (300mg/g) 6. On a stable (\>4 weeks) of sub-maximal RASi dose, defined as any ACE or ARB dose up to and including 50% of maximum dose with evidence of hyperkalaemia potassium level \>5.0mmol/l OR not currently on RASi therapy due to documented issues of hyperkalaemia in the past necessitating RASi discontinuation Exclusion Criteria: 1. Active malignancy 2. Patients who lack capacity to give informed consent 3. GI disturbance/chronic diarrhoea/stoma 4. Subjects with a life expectancy of less than 3 months. 5. Women who are pregnant, lactating, planning to become pregnant or unwilling to use effective methods of contraception during the study. 6. Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated including NYHA class III/IV. 7. History of acute eGFR fall with RASi therapy (\>30% in eGFR on initiation of RASi therapy) 8. Known hypersensitivity or previous anaphylaxis to SZC or Irbesartan 9. Hypotension: BP \<120/70mm/hg at screening despite no antihypertensive agent use 10. Uncontrolled Blood pressure: BP \>170/110 at screening 11. Evidence of prolonged QT on ECG QTc(f)\>550msec 12. History of QT prolongation associated with other medications that required discontinuation of that medication 13. Treatment with lithium, or dual blockade with ACEi and ARB or mineralocorticoid inhibitor 14. History of congenital long QT syndrome 15. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted 16. Current or recent (within 3 months) participation in a clinical trial involving an investigational medicinal product. 17. Current treatment with a potassium binder medication **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** London **Country:** United Kingdom **Facility:** Kieran Mccafferty **State:** Uk **Zip:** E1 1BB ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003920 - Term: Diabetes Mellitus - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000014883 - Term: Water-Electrolyte Imbalance ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Diabetes Mellitus, Type 2 - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M9998 - Name: Hyperkalemia - Relevance: HIGH - As Found: Hyperkalemia - ID: M7123 - Name: Diabetic Nephropathies - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M17624 - Name: Water-Electrolyte Imbalance - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003924 - Term: Diabetes Mellitus, Type 2 - ID: D000006947 - Term: Hyperkalemia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05540379 **Brief Title:** Role of Virtual Reality Simulators in Basic Hysteroscopy Training Competence **Official Title:** Role of Virtual Reality Simulators in Basic Hysteroscopy Training Competence #### Organization Study ID Info **ID:** Hagar Elnashar #### Organization **Class:** INDUSTRY **Full Name:** Egymedicalpedia ### Status Module #### Completion Date **Date:** 2022-04-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-09-14 **Type:** ACTUAL **Last Update Submit Date:** 2022-09-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-04-01 **Type:** ACTUAL #### Start Date **Date:** 2021-05-01 **Type:** ACTUAL **Status Verified Date:** 2022-09 #### Study First Post Date **Date:** 2022-09-14 **Type:** ACTUAL **Study First Submit Date:** 2022-09-09 **Study First Submit QC Date:** 2022-09-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Egymedicalpedia #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Evaluation the efficacy of Virtual Reality simulator training in improving basic gynecological hysteroscopic skills and assess training levels in Ob/Gyn residents, as compared to others with previous hysteroscopic experience. **Detailed Description:** Diagnostic or operative hysteroscopy is one of the most common surgical intervention in gynecological surgery. In recent years, it has acquired a central role in diagnosis and treatment of a variety of uterine pathologies like fibroids, polyps and uterine malformations It is also pivotal in the management of primary or secondary infertility. Biopsy specimens are also sampled with hysteroscopy in the diagnosis of endometrial cancer. In recent years, the technological advancements such as the use of small diameter (3,5mm) rigid hysteroscopes combined with "no touch" techniques have made hysteroscopy a commonly accepted procedure . As a minimally invasive procedure, hysteroscopy is associated with fewer complications than traditional open surgery However, it is challenging to gain manual dexterity in hysteroscopy because of the fulcrum effect and the orientation between the two-dimensional screen and the three-dimensional uterine cavity. Other difficulties are the diminished tactile feedback and limited degrees of freedom, . Lack of proficiency in hysteroscopy can compromise patient safety by causing uterine perforation and trauma to neighboring organs. Also, pulmonary air embolisms and pulmonary edema are potential life-threatening complications. Today it is generally accepted that the traditional apprentice-tutor model is no longer valid for training all skills necessary in Gynecological surgery and more specifically endoscopic surgery This agreement is based on the recognition that, in contrast to open surgery, endoscopic surgery demands surgical skills and psychomotor skills that should not necessarily be trained simultaneously. Increasing evidence strongly suggests that psychomotor skills must be trained earlier and outside the operating room, and several models have been proposed for this aim ### Conditions Module **Conditions:** - Hysteroscopy ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** the efficacy of VR simulator training in improving basic gynecological hysteroscopic skills ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** OTHER #### Enrollment Info **Count:** 102 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** It is about 51 participants whom had performed less than 50 diagnostic hysteroscopies and hysteroscopic polypectomy. **Intervention Names:** - Device: Virtual Reality Training **Label:** Group A: Ob/Gyn physicians **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** It is about 51 participants whom had performed at least 50 diagnostic hysteroscopies and hysteroscopic polypectomy. **Intervention Names:** - Device: Virtual Reality Training **Label:** Group B: Ob/Gyn physicians **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group A: Ob/Gyn physicians - Group B: Ob/Gyn physicians **Description:** Training the obstetrics and Gynecologist Residents on Virtual endoscopic simulation and skills acquisition **Name:** Virtual Reality Training **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** • To compare the final score achieved by the physicians who had performed less than 50 diagnostic hysteroscopies and hysteroscopic polypectomy after 3 training sessions on VR hysteroscopy simulator with the score achieved by physicians who had performed at least 50 diagnostic hysteroscopies and hysteroscopic polypectomy to ensure the role of VR in training for hysteroscopic polypectomy. **Measure:** Virtual Reality Training Score **Time Frame:** from baseline to 6 months after the trainig ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Residents, assistant lecturers, lecturers, associate professors and professors in Ob/Gyn department. 2. Group A: Ob/Gyn physicians who had performed less than 50 diagnostic hysteroscopies and hysteroscopic polypectomy. 3. Group B: Ob/Gyn physicians who had performed at least 50 diagnostic hysteroscopies and hysteroscopic polypectomy. Exclusion Criteria: 1- Physicians who had previously attended VR simulator training course **Maximum Age:** 36 Years **Minimum Age:** 26 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Giza **Country:** Egypt **Facility:** Faculty of Medicine - Cairo University #### Overall Officials **Official 1:** **Affiliation:** Department of obstetrics and gynecology, Faculty Of Medicine, Cairo University **Name:** Ahmed M Fawzi El-Minawi, Professor **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Department of obstetrics and gynecology, Faculty Of Medicine, Cairo University **Name:** Nadine A Sherif, Professor **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03591679 **Brief Title:** Bilateral Uterine Artery Ligation in Reducing Incidence of Postpartum Hemorrhage in Cesarean Section **Official Title:** Role of Bilateral Uterine Artery Ligation in Reducing Incidence of Postpartum Hemorrhage in Cesarean Section in Patients At Risk of Uterine Atony A Randomized Controlled Trial #### Organization Study ID Info **ID:** BUALCS #### Organization **Class:** OTHER **Full Name:** Assiut University ### Status Module #### Completion Date **Date:** 2019-01-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-03-11 **Type:** ACTUAL **Last Update Submit Date:** 2019-03-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-11-30 **Type:** ACTUAL #### Start Date **Date:** 2017-12-01 **Type:** ACTUAL **Status Verified Date:** 2019-03 #### Study First Post Date **Date:** 2018-07-19 **Type:** ACTUAL **Study First Submit Date:** 2018-07-08 **Study First Submit QC Date:** 2018-07-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assiut University #### Responsible Party **Investigator Affiliation:** Assiut University **Investigator Full Name:** Ahmed Mohamed Abbas **Investigator Title:** Principal investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The patients were recruited from women attending labor ward to undergo cesarean section. ### Conditions Module **Conditions:** - Post Partum Hemorrhage ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1070 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients at risk of uterine atony undergoing cesarean section underwent bilateral uterine artery ligation and received oxytocin. **Intervention Names:** - Drug: Oxytocin - Procedure: bilateral uterine artery ligation **Label:** study group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** patients at risk of uterine atony undergoing cesarean section received oxytocin only. **Intervention Names:** - Drug: Oxytocin **Label:** control group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - control group - study group **Description:** 20 units by slow intravenous drip injection **Name:** Oxytocin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - study group **Description:** • The peritoneum over the vesico-uterine pouch already being incised horizontally, the peritoneum over the uterine isthmus and cervix was dissected downwards, and this dissection was then extended laterally. **Name:** bilateral uterine artery ligation **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** by using weight of soaked towels (weight of soaked towel - weight of dry towel) and amount of blood in suction set **Measure:** mean Blood loss after placental separation **Time Frame:** 30 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women with one or more of the following conditions undergoing cesarean section for obstetric indication were included: * Maternal anemia (not less than 7 gm %). * Macrosomic baby \>4kgs. * Twin pregnancy and high order pregnancy. * Polyhydramnios. * Grand multipara. * Previous history of atonic postpartum hemorrhage. * Prolonged vaginal delivery. * Emergency cesarean. * Chorioamnionitis. Exclusion Criteria: * - Placenta previa. * Patients with bleeding tendency (congenital or acquired) * Ante-partum hemorrhage. * Patients with no risk for uterine atony. **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Assiut **Country:** Egypt **Facility:** Ahmed Abbas **State:** Cairo **Zip:** 002 ### References Module #### References **Citation:** Samy A, Ali MK, Abbas AM, Wahab HA, Wali AA, Hussien AH, Mostafa M, Taymour MA, Ogila AI, Ahmad Y, Essam A, Mahmoud M. Randomized controlled trial of the effect of bilateral uterine artery ligation during cesarean among women at risk of uterine atony. Int J Gynaecol Obstet. 2020 Feb;148(2):219-224. doi: 10.1002/ijgo.13064. Epub 2019 Dec 10. **PMID:** 31755559 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000011644 - Term: Puerperal Disorders - ID: D000014592 - Term: Uterine Hemorrhage ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M9559 - Name: Postpartum Hemorrhage - Relevance: HIGH - As Found: Post Partum Hemorrhage - ID: M17341 - Name: Uterine Inertia - Relevance: LOW - As Found: Unknown - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M14499 - Name: Puerperal Disorders - Relevance: LOW - As Found: Unknown - ID: M17340 - Name: Uterine Hemorrhage - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006473 - Term: Postpartum Hemorrhage - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Ancestors - ID: D000010120 - Term: Oxytocics - ID: D000012102 - Term: Reproductive Control Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M13041 - Name: Oxytocin - Relevance: HIGH - As Found: Joint ### Intervention Browse Module - Meshes - ID: D000010121 - Term: Oxytocin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02803879 **Acronym:** HF-CGM **Brief Title:** Assessing the Capability of Cardiogoniometry (CGM) to Detect Changes in Cardiac Resynchronisation Therapy Device Settings **Official Title:** Assessing the Capability of Cardiogoniometry (CGM) to Detect Changes in Cardiac Resynchronisation Therapy Device Settings #### Organization Study ID Info **ID:** 15/NW/0479 #### Organization **Class:** OTHER_GOV **Full Name:** Hull University Teaching Hospitals NHS Trust ### Status Module #### Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-07-08 **Type:** ACTUAL **Last Update Submit Date:** 2019-07-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-07 **Type:** ACTUAL #### Start Date **Date:** 2015-08 **Status Verified Date:** 2019-07 #### Study First Post Date **Date:** 2016-06-17 **Type:** ESTIMATED **Study First Submit Date:** 2016-02-18 **Study First Submit QC Date:** 2016-06-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Hull University Teaching Hospitals NHS Trust #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Some patients with heart failure require treatment called cardiac-resynchronisation therapy (CRT) which involves putting a pacemaker into the heart to make both ventricles (the lower chambers of the heart) contract together, making the pumping of the blood to the rest of the body more efficient. it is important to get the CRT pacemaker checked to make sure that it is working correctly and performing its job. However, it can be difficult to adjust the settings of the pacemaker just the right amount to ensure the heart is pumping efficiently. One of the ways this can be done is by using a special machine which uses ultrasound to make a 2-dimensional image of the heart called an echocardiogram. This technique can also be used to measure the flow of blood in the heart and calculate how efficient it is at pumping blood. However adjusting the settings of the pacemaker with this device is difficult to use and time consuming. Electrocardiogram (ECG) a 2-dimensional electrical tracing of the hearts activity is another tool used to help adjust the settings of pacemakers, to make the heart pump more efficiently. Furthermore, recent research has shown that this is better than echocardiogram at optimising pacemaker device settings. A new type of ECG called cardiogoniometry (CGM) has recently been developed which creates a 3-dimensional view of the hearts electrical activity and has already been shown to be better than normal ECG at diagnosing certain conditions like angina and heart attacks. However it has never been used to try optimise the settings of the pacemakers used in CRT and may be quicker and easier to use than then other methods available. More importantly it is hoped by doing this it will reduce the symptoms that patients suffer as it is making the heart pump more efficiently. As it has been untested and never used in this setting before, and there it is necessary to find out if the CGM machine will recognise when the settings on the pacemaker are changed. The aims of this study is to see if the CGM machine can pick up changes to pacemaker settings, with the hope of running a later study to see if it can be used to optimise settings on the pacemaker used in CRT. **Detailed Description:** Cardiac resynchronisation therapy (CRT) improves symptoms and quality of life and improves the prognosis of patients with chronic heart failure. CRT works by improving co-ordination of cardiac contraction, and is indicated in people with heart failure and left bundle branch block (LBBB) on an ECG. The importance of LBBB is that it indicates that the electricity is spreading only very slowly over the surface of the heart with each heart beat, thereby making contraction very "dyssynchronous"; that is, instead of all the heart muscle contracting simultaneously, parts contract and are relaxing before other parts even start to contract. With a standard pacemaker, a pacing lead is implanted in the right ventricle. In those patients with a normal heart rhythm ("sinus rhythm"), a second lead is usually placed in the right atrium close to the heart's natural pacemaker. The lead in the ventricle can then track the heart's natural heart rate as detected by the lead in the atrium, or, if the natural rate is too slow, the pacemaker can sequentially pace the atrium and then the ventricle. A CRT system is similar, but with the addition of an extra lead positioned to pace the left ventricle. Now, the pacemaker is able to stimulate both left and right ventricles simultaneously, restoring the normal co-ordination of ventricular contraction. Approximately 25% of patients do not achieve significant clinical benefit with CRT. Such patients are termed "non-responders", and lack of response is typically measured as a failure to improve exercise capacity with CRT, or a failure of the heart to improve on echocardiography. One option to reduce the number of non-responders may be to optimise the CRT device by adjusting its settings based on clinical variables (such as ECG and echocardiogram findings). Both ECG and echocardiogram optimisation give similar results in terms of clinical response to CRT, but patients who had their CRT optimised using ECG variables had a significantly greater impact on echocardiographic response, that is a greater proportion of that group had a LV end-systolic volume reduction \>10%) 3. Another possibility for optimising CRT is cardiogoniometry (CGM), which is what the study aims to investigate. CGM is form of 3D vector electrocardiography which can provide quantitative analysis of myocardial depolarisation and repolarisation. Like standard 12 lead electrocardiogram (ECG), CGM uses different electrodes to identify electrical potential gradients produced by cardiac electrical activity. The ECG can only visually represent this information in a two dimensional way, whereas CGM can create a three dimensional display. Electrode placement is important: and complex mathematical modelling is used to generate the displays. CGM gives the same output as a standard ECG. One additional output is vector loop graphs. These are sequentially plotted values of electrical activity of the heart in the x, y and z axis, in three orthogonal planes. When the vector loops follow the same pathway it means that the electrical activity of the heart is following the same pathway with each ventricular depolarisation and repolarisation. By contrast, when there is abnormal electrical conduction, the vector loop pathways can vary. CGM is useful for identifying stable coronary artery disease and recognising the acute coronary syndromes, but its clinical value outside patients with acute ischaemic heart disease is unclear. This feasibility study aims to see if CGM can detect the different settings of a CRT device, by assessing the CGM vector loops with different device settings. ### Conditions Module **Conditions:** - Heart Failure **Keywords:** - cardiac resynchronisation therapy - cardiogoniometry ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All patients attending clinic for follow up appointments following the implantation of a CRT device will be eligible for inclusion in the study. If they consent for enrolment in the study each patient will undergo a series of 4 CGM recordings whilst in their follow up appointment. They will undergo each of these during different pacemaker settings. These are: 1) No pacing, 2) Paced from the right ventricular lead; 3) Paced from the left ventricular lead and 4) Paced from both ventricular leads. After this has been done the participants involvement in the study will have finished. **Intervention Names:** - Device: Cardiogoniometry **Label:** Cardiogoniometry (CGM) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cardiogoniometry (CGM) **Name:** Cardiogoniometry **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Mean cardiac axis of participants when they are not being paced will be calculated with 95% confidence intervals. **Measure:** Mean cardiac axis with no pacing **Time Frame:** Within the first 30 days after end of participant enrollment **Description:** Mean cardiac axis of participants when they are being paced from the RV will be calculated with 95% confidence intervals. **Measure:** Mean cardiac axis with rv pacing **Time Frame:** Within the first 30 days after end of participant enrollment **Description:** Mean cardiac axis of participants when they are being paced from the LV will be calculated with 95% confidence intervals. **Measure:** Mean cardiac axis with lv pacing **Time Frame:** Within the first 30 days after end of participant enrollment **Description:** Mean cardiac axis of participants when they are being biventricular paced will be calculated with 95% confidence intervals. **Measure:** Mean cardiac axis with biv pacing **Time Frame:** Within the first 30 days after end of participant enrollment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients attending follow up clinic with a CRT device implanted. * Patients have to be receiving CRT therapy - in other words, the device has to be functioning correctly. * Aged 18 or over. * The patient has been informed of the nature of the study and has provided full written informed consent. Exclusion Criteria: * Patients unable to give informed consent including those with communication difficulties due to poor English. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Kingston upon Hull **Country:** United Kingdom **Facility:** Castle Hill Hospital **State:** East Yorkshire **Zip:** HU16 5JQ ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Brown OI, Nikolaidou T, Beddoes G, Hoye A, Clark AL. The HF-CGM Study: An Analysis of Cardiogoniometric Axes in Patients With Cardiac Resynchronization Therapy. IEEE Trans Biomed Eng. 2018 Aug;65(8):1711-1716. doi: 10.1109/TBME.2017.2769060. Epub 2017 Nov 2. **PMID:** 29989935 #### See Also Links **Label:** Abstract Link **URL:** https://www.ncbi.nlm.nih.gov/pubmed/29989935?dopt=Abstract ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03013179 **Acronym:** InterGEN **Brief Title:** Intergenerational Blood Pressure Study **Official Title:** Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure #### Organization Study ID Info **ID:** 1311012986 #### Organization **Class:** OTHER **Full Name:** Yale University #### Secondary ID Infos **ID:** 5R01NR013520 **Link:** https://reporter.nih.gov/quickSearch/5R01NR013520 **Type:** NIH ### Status Module #### Completion Date **Date:** 2020-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-20 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-06 **Type:** ACTUAL #### Start Date **Date:** 2015-04 **Type:** ACTUAL **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2017-01-06 **Type:** ESTIMATED **Study First Submit Date:** 2017-01-05 **Study First Submit QC Date:** 2017-01-05 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Nursing Research (NINR) **Class:** OTHER **Name:** Emory University #### Lead Sponsor **Class:** OTHER **Name:** Yale University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This project, the Intergenerational Blood Pressure Study, is a 5 year research study funded by the National Institutes of Health/National Institute of Nursing Research and led by the Yale University School of Nursing and The Consultation Center at the Yale University School of Medicine, Department of Psychiatry in partnership with Head Start programs across CT. The investigators seek to reduce hypertension health disparities among underserved Black/African American children and their mothers by conducting community-based research to better understand the genetic, psychological, and environmental factors that may contribute to high blood pressure. **Detailed Description:** This study will examine: (1) the impact of (GXE) genetic and psychological environmental factors (discrimination, depression, and parenting behaviors) on the health of African American (AA) children aged 3 through 5 years and (2) the GXE risk for hypertension (HTN) in AA women and children. The overall goal of this project is to delineate the psychobiological (GXE interaction) mechanisms through which AA mothers' perceived racial discrimination, mental health, and parenting behavior affect their own and their young children's blood pressure (BP) over time. The research will examine both genetic (candidate gene and epigenetic effects) and psychological (maternal perceived racial discrimination, mental health, and parenting behavior) interaction effects on BP on this population. The investigators will employ a psychobiological approach by: utilizing psychological and biological assessments using a longitudinal cohort research design, a 2-step candidate gene and epigenetic methodology, and use of ancestry informative markers to account for population stratification admixture to explore GXE interactions on BP in AA mothers and children. Data analysis for the study will be conducted using multiple mixed modeling, cross-validation, and false discovery rate methods. The investigators will enroll 250 AA children aged 3 through 5 years and their (n=250) mothers/maternal caregivers. The investigators will assess mother and child factors every six months for 2 years. The investigators propose the following: Aim 1: Examine the GXE interaction and epigenetic effects of mothers' perceived racial discrimination and its influence on BP over a period of two years. Aim 2: Examine the GXE interaction and epigenetic effects of mothers' mental health status \[symptoms of depression\] and its influence on BP over a period of two years. Aim 3: Examine the GXE interaction and epigenetic effects of mothers' parenting behavior and its influence on BP over a period of two years. This project supports the National Institute of Nursing Research mission "to promote and improve the health of individuals, families, communities, and populations" by conducting basic research on the health and illness of women and young children. The proposed research extends nursing science by integrating the biological (genetics) and behavioral (psychology) components that can inform the combination of multi-level factors that contribute to AAs having the highest incidence of HTN in the US. Findings from this project can contribute to developing interventions that address genetic and psychological factors to reduce these risks for HTN. ### Conditions Module **Conditions:** - Hypertension ### Design Module #### Bio Spec **Description:** Saliva sample for DNA **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 500 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Black/African American Women and their 3-5 year old children ### Outcomes Module #### Primary Outcomes **Description:** Manual blood pressure taken according to JNC-7 guidelines, average of 3 resting blood pressure measurements **Measure:** Blood Pressure **Time Frame:** 18 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Mothers must: * Self-identify as Black/African American * Be 21 years or older * Have a 3-5 year old biological child * Not be impaired by a though disorder, psychosis, or mania * Confirm that their child will be able to provide saliva sample for DNA * Be English-speaking Exclusion Criteria: * None **Healthy Volunteers:** True **Minimum Age:** 3 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Black/African American women and their 3-5 year old children in CT ### Contacts Locations Module #### Locations **Location 1:** **City:** Orange **Country:** United States **Facility:** Yale University School of Nursing **State:** Connecticut **Zip:** 06477 #### Overall Officials **Official 1:** **Affiliation:** Yale University **Name:** Jacquelyn Y Taylor, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Yale University **Name:** Cindy A Crusto, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Genomic Data Sharing Plan in place, in accordance with NIH regulations Only de-identified genomic data will be shared with dbGaP, to which other researchers will be able to apply for access. Data will be submitted within 1 year after analyses are complete. **IPD Sharing:** YES ### References Module #### References **Citation:** Taylor JY, Wright ML, Crusto CA, Sun YV. The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) Study: Design and Methods for Complex DNA Analysis. Biol Res Nurs. 2016 Oct;18(5):521-30. doi: 10.1177/1099800416645399. Epub 2016 Apr 26. **PMID:** 27118148 **Citation:** Crusto CA, Barcelona de Mendoza V, Connell CM, Sun YV, Taylor JY. The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure Study (InterGEN): Design and Methods for Recruitment and Psychological Measures. Nurs Res. 2016 Jul-Aug;65(4):331-8. doi: 10.1097/NNR.0000000000000163. **PMID:** 27362519 **Citation:** Barcelona de Mendoza V, Wright ML, Agaba C, Prescott L, Desir A, Crusto CA, Sun YV, Taylor JY. A Systematic Review of DNA Methylation and Preterm Birth in African American Women. Biol Res Nurs. 2017 May;19(3):308-317. doi: 10.1177/1099800416669049. Epub 2016 Sep 19. **PMID:** 27646016 #### See Also Links **Label:** Click here for more information about this study: Intergenerational Blood Pressure Study **URL:** http://intergen.yale.edu/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006973 - Term: Hypertension ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01116479 **Acronym:** HaemOPtimal **Brief Title:** Optimal Transfusion in Anaemic Cancer Patients Treated With Chemotherapy (HaemOPtimal) **Official Title:** Randomised Feasibility Study of Optimal Transfusion Thresholds in Anaemic Cancer Patients Treated With Chemotherapy (HaemOPtimal) #### Organization Study ID Info **ID:** H-1-2009-109 #### Organization **Class:** OTHER **Full Name:** Rigshospitalet, Denmark ### Status Module #### Completion Date **Date:** 2013-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-11-05 **Type:** ESTIMATED **Last Update Submit Date:** 2014-11-03 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2013-12 **Type:** ACTUAL #### Start Date **Date:** 2010-03 **Status Verified Date:** 2014-11 #### Study First Post Date **Date:** 2010-05-05 **Type:** ESTIMATED **Study First Submit Date:** 2010-04-28 **Study First Submit QC Date:** 2010-05-04 **Why Stopped:** low accrual ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Rigshospitalet, Denmark #### Responsible Party **Investigator Affiliation:** Rigshospitalet, Denmark **Investigator Full Name:** Morten Sorensen **Investigator Title:** MD, PhD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This an open two-arm interventional randomised feasibility study in anaemic patients treated with chemotherapy. Randomisation is performed between two transfusion thresholds: Haemoglobin \< 6.0 mmol/l (9.9 g/dL) versus haemoglobin \< 7.1 mmol/l (11.7 g/dL) for female and 8.1 mmol/l (13.4 g/dL) for males.Primary end-point is quality of life **Detailed Description:** Title: Randomised Feasibility Study of Optimal Transfusion Thresholds in Anaemic Cancer Patients Treated with Chemotherapy (HaemOPtimal) Background: Cancer patients treated with chemotherapy very often become anaemic, which have profound negative impact of their quality of life. Blood transfusions can ameliorate symptoms caused by anaemia. Data are lagging with regard to what threshold should be used when offering blood transfusion. Aim: The primary aim is to determine which end-points reflect symptoms caused by anaemia in cancer patients treated with chemotherapy. The secondary aims are to collect data to estimate sample size in a future definitive study and to compare symptom relief using to different transfusion thresholds. End-points: * Numeric Rating Scale measuring fatigue, dizziness, palpitations, headache, and dyspnea. * FACT-G, * FACT-An (Total anemia scale) including a fatigue subscale * Patient-assessed WHO performance status Design: Open two-arm interventional randomised feasibility study Intervention: * Blood transfusion. * Randomisation between two transfusion thresholds: Haemoglobin \< 6.0 mmol/l (9.9 g/dL) versus Haemoglobin \< 7.1 mmol/l (11.7 g/dL) for female and 8.1 mmol/l (13.4 g/dL) for males. Population: Cancer patients treated with chemotherapy Inclusion criteria: * Documented cancer * Planned treatment with chemotherapy * Age 18 years or older * Informed consent Exclusion criteria: * Heart failure (NYHA 3 and 4) * Prior serious complications to blood transfusion * Medical conditions that require special considerations for blood transfusion * Treatment with erythropoiesis-stimulating agents. Number of patients: Transfusion of at least 30 patients in each intervention arm. An estimated number of 90 patients will be randomised in each arm (180 in total) as a third of included patients are expected to require transfusion. ### Conditions Module **Conditions:** - Cancer - Anaemia **Keywords:** - Anaemia, transfusion, cancer, chemotherapy, Quality of life ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 180 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Blood transfusion thresholds:Haemoglobin \< 6.0 mmol/l (9.9 g/dL) **Intervention Names:** - Other: Blood transfusion **Label:** Haemoglobin (<6.0 mmol/l) **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Blood transfusion threshold: Haemoglobin \< 7.1 mmol/l (11.7 g/dL) for female and 8.1 mmol/l (13.4 g/dL) for males **Intervention Names:** - Other: Blood transfusion **Label:** Haemoglobin (< normal range) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Haemoglobin (< normal range) - Haemoglobin (<6.0 mmol/l) **Description:** Blood transfusion with packed erythrocytes **Name:** Blood transfusion **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Patient assessed FACT-G (Functional Assessment of Therapy in General), FACT-An (Functional Assessment of Therapy in Anaemia), Numeric Rating Scale on symptoms of anaemia (fatigue, dizziness, dyspnea, palpitations, headache) and performance status before each cycle of chemotherapy, before transfusion and daily in seven days after transfusion **Measure:** FACT-G, FACT-An, Numeric Rating Scale on symptoms of anaemia, Performance status **Time Frame:** Before each cylces of chemotherapy in up to six months, and before transfusion, and daily in seven days after transfusion #### Secondary Outcomes **Description:** Frequency of complications to blood transfusion (need for termination of transfusion due to complications, chills, fever, hives, drop in blood pressure, dyspnea, other) **Measure:** Safety and transfusion complications **Time Frame:** during or after transfusion ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Documented cancer * Planned treatment with chemotherapy * Age older than 18 years * Informed consent Exclusion Criteria: * Heart failure (NYHA 3 and 4) * Prior serious complications to blood transfusion * Medical conditions that require special considerations for blood transfusion * Treatment with erythropoiesis-stimulating agents **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Copenhagen **Country:** Denmark **Facility:** Blood bank, Righospitalet **Zip:** DK-2100 **Location 2:** **City:** Copenhagen **Country:** Denmark **Facility:** Dept. of Oncology, Rigshospitalet **Zip:** DK-2100 #### Overall Officials **Official 1:** **Affiliation:** Dept. of Oncology, Righospitalet, Denmark **Name:** Morten Sorensen, MD, Phd **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5. **PMID:** 34932836 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006402 - Term: Hematologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M4070 - Name: Anemia - Relevance: HIGH - As Found: Anemia - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000740 - Term: Anemia ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M207501 - Name: Chrysarobin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00488579 **Acronym:** PROFEG **Brief Title:** Routine Iron Prophylaxis During Pregnancy **Official Title:** Routine Iron Prophylaxis During Pregnancy - Effects on Maternal and Child Health in Maputo City and Province (Mozambique) #### Organization Study ID Info **ID:** PROFEG #### Organization **Class:** OTHER_GOV **Full Name:** National Istitute For Health and Welfare, Finland ### Status Module #### Completion Date **Date:** 2016-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-11-30 **Type:** ACTUAL **Last Update Submit Date:** 2017-11-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-12 **Type:** ACTUAL #### Start Date **Date:** 2007-05 **Status Verified Date:** 2017-11 #### Study First Post Date **Date:** 2007-06-20 **Type:** ESTIMATED **Study First Submit Date:** 2007-06-19 **Study First Submit QC Date:** 2007-06-19 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Academy of Finland #### Lead Sponsor **Class:** OTHER_GOV **Name:** National Istitute For Health and Welfare, Finland #### Responsible Party **Investigator Affiliation:** National Istitute For Health and Welfare, Finland **Investigator Full Name:** Elina Hemminki **Investigator Title:** MD, Research Professor, THL **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Comparison of two policies of iron administration during pregnancy in regard to health and program feasibility in an area with endemic malaria and high prevalence of HIV infection. The policies are: 1) routine iron prophylaxis, 2) screening and therapy with iron. **Detailed Description:** Aim of the study: Comparison of two policies of iron administration during pregnancy in regard to health of the mother and infant and program feasibility. The two groups compared are: 1. Routine iron prophylaxis 2. Screening of anaemia and therapy with iron Hypothesis: group 2 will have better health outcomes. Study groups: Routine group: 60 mg per day of ferrous sulphate (combination with folic acid) daily. Screening and therapy: Hb measurement on each visit, Hb \>9g/dl Þ only folic acid, Hb \<9g/dl Þ 60/120 mg of ferrous sulphate daily(+ folic acid) Methods: A pragmatic randomised controlled trial with non-blind design. Total intended sample size was 4000 women. Study site: Mozambique, Maputo City. Women are randomised individually and allocated into the two groups; 1) Routine iron prophylaxis, 2) Screening and therapy for anemia. The recruitment of pregnant women was done in two health centres, one in Maputo city and one in Maputo Province. The women are followed in prenatal visits and until delivery. ### Conditions Module **Conditions:** - Pregnancy **Keywords:** - iron prophylaxis - pregnancy - birth weight - prematurity - perinatal mortality ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 4326 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** giving 60 mg ferrous sulphate daily (+folic acid) **Intervention Names:** - Drug: Two policies of iron prophylaxis **Label:** routine iron prophylaxis **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** doing Hb measurement on each visit, Hb\>9g/dl giving only folic acid, Hb\<9g/dl giving 60-120 mg of ferrous sulphate daily (+folic acid) **Intervention Names:** - Drug: Two policies of iron prophylaxis **Label:** screening and therapy **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - routine iron prophylaxis - screening and therapy **Description:** 60mg ferrous sulphate daily (+folic acid); Screening and therapy: Hb measurement on each visit, Hb\>9g/dl only folic acid, Hb\<9g/dl 60-120 of ferrous sulphate daily (+folic acid). **Name:** Two policies of iron prophylaxis **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Birth \<37 gestational weeks **Measure:** Preterm delivery **Time Frame:** Until birth **Description:** weight \<2500g **Measure:** Low birth weight **Time Frame:** At birth #### Secondary Outcomes **Measure:** perinatal mortality, complications during pregnancy and birth **Time Frame:** pregnancy and neonatal period ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pregnant women at their first prenatal visit Exclusion Criteria: * Women under 18 years, high obstetric risk pregnancies **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Maputo **Country:** Mozambique **Facility:** Universidade Eduardo Mondlande, Faculty of Medicine, Department of Community Health #### Overall Officials **Official 1:** **Affiliation:** THL **Name:** Elina Hemminki, PhD, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Eduardo Mondlane University **Name:** Baltazar Chilundo **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Hemminki E, Nwaru BI, Salome G, Parkkali S, Abacassamo F, Augusto O, Cliff J, Regushevskaya E, Dgedge M, Sousa C, Chilundo B. Is selective prenatal iron prophylaxis better than routine prophylaxis: final results of a trial (PROFEG) in Maputo, Mozambique. BMJ Open. 2016 Jun 13;6(6):e011280. doi: 10.1136/bmjopen-2016-011280. **PMID:** 27297013 **Citation:** Nwaru BI, Salome G, Abacassamo F, Augusto O, Cliff J, Sousa C, Regushevskaya E, Parkkali S, Hemminki E. Adherence in a pragmatic randomized controlled trial on prophylactic iron supplementation during pregnancy in Maputo, Mozambique. Public Health Nutr. 2015 Apr;18(6):1127-34. doi: 10.1017/S1368980014001359. Epub 2014 Jul 7. **PMID:** 24999785 **Citation:** Parkkali S, Abacassamo F, Nwaru BI, Salome G, Augusto O, Regushevskaya E, Dgedge M, Sousa C, Cliff J, Chilundo B, Hemminki E. Comparison of routine prenatal iron prophylaxis and screening and treatment for anaemia: pregnancy results and preliminary birth results from a pragmatic randomised controlled trial (PROFEG) in Maputo, Mozambique. BMJ Open. 2013 Feb 8;3(2):e001948. doi: 10.1136/bmjopen-2012-001948. Print 2013. **PMID:** 23396557 **Citation:** Nwaru BI, Parkkali S, Abacassamo F, Salome G, Chilundo B, Augusto O, Cliff J, Dgedge M, Regushevskaya E, Nikula M, Hemminki E. A pragmatic randomised controlled trial on routine iron prophylaxis during pregnancy in Maputo, Mozambique (PROFEG): rationale, design, and success. Matern Child Nutr. 2015 Apr;11(2):146-63. doi: 10.1111/mcn.12006. Epub 2012 Oct 1. **PMID:** 23020829 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M25869 - Name: Premature Birth - Relevance: LOW - As Found: Unknown - ID: M5006 - Name: Birth Weight - Relevance: LOW - As Found: Unknown - ID: M30666 - Name: Perinatal Death - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins - Abbrev: Mi - Name: Mineral ### Intervention Browse Module - Browse Leaves - ID: M10533 - Name: Iron - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - Relevance: LOW - As Found: Unknown - ID: T446 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: T448 - Name: Folate - Relevance: LOW - As Found: Unknown - ID: T475 - Name: Vitamin B9 - Relevance: LOW - As Found: Unknown - ID: T341 - Name: Iron Supplement - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24