- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04504032
A Trial to Evaluate Safety and Efficacy of Rivaroxaban (COVID-19)
October 20, 2021 updated by: Bill & Melinda Gates Medical Research Institute
A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19
The purpose of this study is to assess safety and clinical efficacy of rivaroxaban in people with mild Coronavirus Disease 2019 who are at increased risk of disease progression.
Study Overview
Study Type
Interventional
Enrollment (Actual)
497
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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London, United Kingdom, NW3 2Q
- Royal Free Hospital
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Cheshire
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Sale, Cheshire, United Kingdom, M33 2RH
- Boundary House Medical Centre
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City Of London
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London, City Of London, United Kingdom, W2 1NY
- St Mary's Hospital - PPDS
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Arkansas
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Rogers, Arkansas, United States, 72758
- Woodland Research Northwest LLC - ERG - PPDS
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California
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Los Angeles, California, United States, 90094
- Science 37, Inc
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San Diego, California, United States, 92123
- Allergy and Asthma Medical Group and Research Center - CRN - PPDS
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Florida
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Fort Lauderdale, Florida, United States, 33308
- InvesClinic, LLC
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Loxahatchee Groves, Florida, United States, 33470
- Advanced Pulmonary Research Institute
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Miami, Florida, United States, 33126
- LCC Medical Research - Miami - BTC - PPDS
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Mount Dora, Florida, United States, 32757
- Adult Medicine of Lake County
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Illinois
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Evergreen Park, Illinois, United States, 60805
- Providea Health Partners LLC
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Minnesota
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Minneapolis, Minnesota, United States, 55402
- Clinical Research Institute, Inc - CRN - PPDS
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Nevada
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North Las Vegas, Nevada, United States, 89086
- Encompass Care
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New Jersey
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Secaucus, New Jersey, United States, 07094
- Riverside Medical Group - Circuit- PPDS
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New York
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Bronx, New York, United States, 10451
- NYC Health + Hospitals/Lincoln
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Elmhurst, New York, United States, 11373
- Elmhurst Hospital Center
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New York, New York, United States, 10037
- Harlem Hospital Center
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Texas
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Austin, Texas, United States, 78735
- Premier Family Physicians - Austin - Hunt - PPDS
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Plano, Texas, United States, 75024
- Village Health Partners - Plano - Hunt - PPDS
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San Antonio, Texas, United States, 78229
- South Texas Allergy and Asthma Medical Professionals
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
Participants must be at high-risk for Coronavirus disease 2019 (COVID-19) disease progression by fulfilling at least one of the following criteria at screening:
- Presence of chronic pulmonary disease, chronic obstructive pulmonary disease (COPD), pulmonary hypertension
- Diabetes mellitus (type 1 or type 2), requiring oral medication or insulin for treatment
- Hypertension, requiring at least one oral medication for treatment
- Immunocompromised status due to disease (e.g., those living with human immunodeficiency virus with a cluster of differentiation 4 [CD4] T-cell count of <200 per cubic millimeter [mm^3])
- Immunocompromised status due to medication (e.g., taking 20 milligram [mg] or more of prednisone equivalents a day, anti-inflammatory monoclonal antibody therapies, cancer therapies)
- Any chronic disease that is associated with high risk for severe COVID in the opinion of the site investigator
- Body mass index ≥35 Kilogram per square meter (kg/m^2) (based on self-reported weight and height).
- Documented Severe Acute Respiratory Syndrome Coronavirus 2 positive diagnostic test of ≤7 days at the time of screening
- Symptomatic for COVID-19 for ≤72 hours at the time of screening (defined as having at least 2 of the following symptoms of COVID-19 that is of new onset or has worsened from baseline, and include fever, chills, myalgia, arthralgia, headache, fatigue, cough, sore throat, nasal congestion, anosmia, ageusia, nausea, vomiting, or diarrhea. If only two symptoms are present, they cannot both be anosmia and ageusia)
- Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the inform consent form and in this protocol
- Agree to participate in all remote, in-person or home visits as required in the protocol and provide updated contact information as necessary.
- Female of childbearing potential must agree to practice adequate contraception during the study
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Currently hospitalized or under immediate consideration for hospitalization at screening and Day 1
- Have new onset shortness of breath or increased shortness of breath from pre-COVID-19 (for people with known COPD) at screening and Day 1
- Hypoxemia (oxygen saturation <94% in ambient air or oxygen saturation below pre-COVID-19 level for people with known COPD) at Day 1
- Require supplemental oxygen (new requirement or increase in requirement from pre-COVID-19 condition) at screening and Day 1
- Have a history of (in the past 3 months) or current active pathological bleeding
- Have a history of hemorrhagic stroke or intracranial hemorrhage
- Have a recent severe head trauma within 30 days which includes concussion, skull fracture or hospitalization for head injury
- Have known intracranial neoplasm, cerebral metastases, arteriovenous malformation or aneurysm
- Have history of pregnancy-related hemorrhage
- Have active gastroduodenal ulcer or other gastrointestinal bleeding diagnosed in the past 3 months
- Currently are in a hemodynamically unstable state
- Currently require thrombolysis or pulmonary embolectomy
- Have history of severe hypersensitivity reaction to Xarelto®
- Currently have a prosthetic heart valve
- Have known diagnosis of triple positive antiphospholipid syndrome
- Have known diagnosis of chronic kidney disease (stage IV or receiving dialysis)
- Have a history of thrombocytopenia or known platelet count <100,000 cells/mm^3
- Have history of bronchiectasis and pulmonary cavitation
- Have active cancer (e.g, receiving chemotherapy or treatment for complication of the active cancer)
- Had epidural or neuraxial anesthesia or spinal puncture in the past 2 weeks and plan to undergo these procedures during the study
- Had surgery in the past 4 weeks or plan to undergo surgery during the study
- Currently is pregnant or plans to become pregnant
- Currently is breastfeeding
- Share household with an enrolled participant in this study
- Co-enrollment in any clinical trial that includes prohibited procedures (spinal puncture or surgery) or that includes treatments within the same drug class as rivaroxaban or treatments for which co-administration with rivaroxaban are prohibited. Note that any co-enrollment other than this requires approval by the Sponsor. For any co-enrolled study, the total volume of blood samples collected across the studies should not exceed 275 milliliters (mL) in 4 weeks.
Currently using and plan to use the following medications during the study
- Rivaroxaban or drugs in the same class
- Dual anti-platelets therapy
- Other anticoagulants
- Combined Permeability glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) inhibitors and inducers
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
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Experimental: Rivaroxaban
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Participants self-administered rivaroxaban, 10 milligrams (mg) (1 tablet) orally once daily for 21 days.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35
Time Frame: Up to Day 35
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An AE is any untoward medical occurrence that occurs in a participant.
An AE can be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with treatment, whether considered related to the product.
AEs may include the onset of a new illness or undesirable medical condition or the exacerbation of pre-existing medical conditions.
AE severity was graded as Grade 3 (Severe) and Grade 4 (Potentially Life-threatening) per the specific toxicity grading by the Division of Acquired Immunodeficiency Syndrome (DAIDS) AE Grading Table.
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Up to Day 35
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Number of Participants With AEs Resulting in Study Intervention Discontinuation Through Day 35
Time Frame: Up to Day 35
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An AE is any untoward medical occurrence that occurs in a participant.
An AE can be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with treatment, whether considered related to the product.
AEs may include the onset of new illness or undesirable medical condition or the exacerbation of pre-existing medical conditions.
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Up to Day 35
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Number of Participants With Serious Adverse Events Through Day 35
Time Frame: Up to Day 35
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A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other outcomes.
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Up to Day 35
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Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale Through Day 28
Time Frame: Up to Day 28
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Participants who progressed to a moderate or severe disease category or higher (Bill & Melinda Gates Medical Research Institute [Gates MRI] ordinal scale ≥3) are reported.
Gates MRI scale scores are assessed on a 7-point scale: 1=Asymptomatic/symptoms similar to pre-COVID-19 status; 2=Mild; 3=Moderate or severe; 4=Critically ill; 5=Critically ill with invasive mechanical ventilation or extrapulmonary complication; 6=Critically ill with Extra-Corporeal Membrane Oxygenation (ECMO); 7=Death.
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Up to Day 28
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Time to Disease Resolution Based on Symptoms Resolution Through Day 28
Time Frame: Up to Day 28
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Time to disease resolution is defined as the time from the first dose to the date of symptoms resolution (new-onset Coronavirus Disease 2019 [COVID-19] symptoms resolved, and pre-existing symptoms returned to Baseline) through Day 28.
Baseline refers to health status prior to contracting new-onset COVID-19 symptoms.
The 95% confidence interval (CI) for median and quartiles of time to disease resolution were calculated using the Kaplan Meier estimates.
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Up to Day 28
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Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through Day 28
Time Frame: Up to Day 28
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Time to disease resolution is defined as the time from the first dose to the date of both viral clearance (two consecutive negative diagnostic tests) and symptoms resolution (new-onset COVID-19 symptoms resolved, and pre-existing symptoms returned to Baseline) through Day 28.
Baseline refers to health status prior to contracting new-onset COVID-19 symptoms.
The 95% CI for median and quartiles of time to disease resolution were calculated using the Kaplan Meier estimates.
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Up to Day 28
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Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale at Day 8, 14, and 21
Time Frame: Days 8, 14, and 21
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Participants who progressed to a moderate or severe disease category or higher (Gates MRI ordinal scale ≥3) are reported.
Gates MRI ordinal scale scores are assessed on a 7-point scale: 1=Asymptomatic/symptoms similar to pre-COVID-19 status; 2=Mild; 3=Moderate or severe; 4=Critically ill; 5=Critically ill with invasive mechanical ventilation or extrapulmonary complication; 6=Critically ill with ECMO; 7=Death.
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Days 8, 14, and 21
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Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at Days 8, 14, 21, and 28
Time Frame: Days 8, 14, 21, and 28
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Symptoms resolution is defined as new-onset COVID-19 symptoms resolved, and pre-existing symptoms returned to Baseline.
Baseline refers to health status prior to contracting new-onset COVID-19 symptoms.
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Days 8, 14, 21, and 28
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Number of Participants Who Achieved Disease Resolution Based on Viral Clearance and Symptoms Resolution at Days 8, 14, 21, and 28
Time Frame: Days 8, 14, 21, and 28
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Viral clearance is defined as two consecutive negative diagnostic tests.
Symptoms resolution is defined as new-onset COVID-19 symptoms resolved, and pre-existing symptoms returned to Baseline.
Baseline refers to health status prior to contracting new-onset COVID-19 symptoms.
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Days 8, 14, 21, and 28
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Number of Participants With the Indicated Gates Medical Research Institute (MRI) Scale Clinical Status at Days 8, 14, 21, and 28
Time Frame: Days 8, 14, 21, and 28
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Participants who progressed to a moderate or severe disease category or higher (Gates MRI ordinal scale ≥3) are reported.
Gates MRI ordinal scale scores are assessed on a 7-point scale: 1=Asymptomatic/symptoms similar to pre-COVID-19 status; 2=Mild; 3=Moderate or severe; 4=Critically ill; 5=Critically ill with invasive mechanical ventilation or extrapulmonary complication; 6=Critically ill with ECMO; 7=Death.
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Days 8, 14, 21, and 28
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Number of Participants With the Indicated World Health Organization (WHO) Ordinal Scale Clinical Status at Days 8, 14, 21, and 28
Time Frame: Days 8, 14, 21, and 28
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The WHO ordinal scale score is used to analyze the overall burden of disease and disease severity using an 11-point scale ranging from 0 to 10: 0=Uninfected; No viral ribonucleic acid (RNA) detected; 1=Asymptomatic; viral RNA detected; 2=Symptomatic; independent; 3=Symptomatic; assistance needed; 4=Hospitalized; no oxygen therapy (for isolation only); 5=Hospitalized; oxygen by mask or nasal prongs; 6=Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow; 7=Intubation and mechanical ventilation, partial pressure of oxygen (pO2)/fraction of inspired oxygen (FiO2) ≥150 or oxygen saturation (SpO2)/FiO2 ≥200; 8=Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or Vasopressors; 9=Mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis, or ECMO; 10=Dead.
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Days 8, 14, 21, and 28
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Number of Participants With Hospitalization Through Days 8, 14, 21, and 28
Time Frame: Days 8, 14, 21, and 28
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Participants who had clinical worsening and who had at least one hospitalization during the study were analyzed.
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Days 8, 14, 21, and 28
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Median Number of Days of Hospitalization Through Day 35
Time Frame: Up to Day 35
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Participants who had clinical worsening and who had at least one hospitalization during the study were analyzed.
Hospitalized participants without an end date of hospitalization were not included.
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Up to Day 35
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Shift in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
Time Frame: Days 8, 14, 21, and 28
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Gates MRI ordinal scale scores are assessed on a 7-point scale: 1=Asymptomatic/symptoms similar to pre-COVID-19 status; 2=Mild; 3=Moderate or severe; 4=Critically ill; 5=Critically ill with invasive mechanical ventilation or extrapulmonary complication; 6=Critically ill with ECMO; 7=Death.
BS= Baseline; PBS= Post-Baseline; NA= Data not available.
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Days 8, 14, 21, and 28
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Shift in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
Time Frame: Baseline; Days 8, 14, 21, and 28
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The WHO ordinal scale score is used to analyze the overall burden of disease and disease severity using an 11-point scale ranging from 0 to 10: 0=Uninfected; No viral ribonucleic acid (RNA) detected; 1=Asymptomatic; viral RNA detected; 2=Symptomatic; independent; 3=Symptomatic; assistance needed; 4=Hospitalized; no oxygen therapy (for isolation only); 5=Hospitalized; oxygen by mask or nasal prongs; 6=Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow; 7=Intubation and mechanical ventilation, partial pressure of oxygen (pO2)/fraction of inspired oxygen (FiO2) ≥150 or oxygen saturation (SpO2)/FiO2 ≥200; 8=Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or Vasopressors; 9=Mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis, or ECMO; 10=Dead.
BS= Baseline; PBS= Post-Baseline; NA= Data not available.
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Baseline; Days 8, 14, 21, and 28
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
Time Frame: Baseline; Days 8, 14, 21, and 28
|
Gates MRI ordinal scale scores are assessed on a 7-point scale: 1=Asymptomatic/symptoms similar to pre- COVID-19 status; 2=Mild; 3=Moderate or severe; 4=Critically ill; 5=Critically ill with invasive mechanical ventilation or extrapulmonary complication; 6=Critically ill with ECMO; 7=Death.
Instead of change from baseline, shift in scores from baseline was measured and have been presented in outcome measure 14.
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Baseline; Days 8, 14, 21, and 28
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Change From Baseline in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
Time Frame: Baseline; Days 8, 14, 21, and 28
|
The WHO ordinal scale score is used to analyze the overall burden of disease and disease severity using an 11-point scale ranging from 0 to 10: 0=Uninfected; No viral ribonucleic acid (RNA) detected; 1=Asymptomatic; viral RNA detected; 2=Symptomatic; independent; 3=Symptomatic; assistance needed; 4=Hospitalized; no oxygen therapy (for isolation only); 5=Hospitalized; oxygen by mask or nasal prongs; 6=Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow; 7=Intubation and mechanical ventilation, partial pressure of oxygen (pO2)/fraction of inspired oxygen (FiO2) ≥150 or oxygen saturation (SpO2)/FiO2 ≥200; 8=Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or Vasopressors; 9=Mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis, or ECMO; 10=Dead.
Instead of change from baseline, shift in scores from baseline was measured and have been presented in outcome measure 16.
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Baseline; Days 8, 14, 21, and 28
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: GatesMRI, Bill & Melinda Gates Medical Research Institute
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 2, 2020
Primary Completion (Actual)
March 10, 2021
Study Completion (Actual)
March 29, 2021
Study Registration Dates
First Submitted
August 5, 2020
First Submitted That Met QC Criteria
August 5, 2020
First Posted (Actual)
August 7, 2020
Study Record Updates
Last Update Posted (Actual)
October 22, 2021
Last Update Submitted That Met QC Criteria
October 20, 2021
Last Verified
October 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- COVID-19
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Factor Xa Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Rivaroxaban
Other Study ID Numbers
- Gates MRI - COD-01-T01-01
- 2020-005395-35 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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