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A Trial to Evaluate Safety and Efficacy of Rivaroxaban (COVID-19)

Sponsor
Bill & Melinda Gates Medical Research Institute (Other)
Overall Status
Terminated
CT.gov ID
NCT04504032
Collaborator
(none)
497
Enrollment
20
Locations
2
Arms
6.8
Actual Duration (Months)
24.9
Patients Per Site
3.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
497 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19
Actual Study Start Date :
Sep 2, 2020
Actual Primary Completion Date :
Mar 10, 2021
Actual Study Completion Date :
Mar 29, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Rivaroxaban

Drug: Rivaroxaban
Participants self-administered rivaroxaban, 10 milligrams (mg) (1 tablet) orally once daily for 21 days.
Placebo Comparator: Placebo

Drug: Placebo
Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35 [Up to Day 35]

    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.

  2. Number of Participants With AEs Resulting in Study Intervention Discontinuation Through Day 35 [Up to Day 35]

    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.

  3. Number of Participants With Serious Adverse Events Through Day 35 [Up to Day 35]

    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.

  4. Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale Through Day 28 [Up to Day 28]

    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.

Secondary Outcome Measures

  1. Median Time to Disease Resolution Based on Symptoms Resolution Through Day 28 [Up to Day 28]

    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.

  2. Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through Day 28 [Up to Day 28]

    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.

  3. 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 [Days 8, 14, and 21]

    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.

  4. Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at Days 8, 14, 21, and 28 [Days 8, 14, 21, and 28]

    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.

  5. Number of Participants Who Achieved Disease Resolution Based on Viral Clearance and Symptoms Resolution at Days 8, 14, 21, and 28 [Days 8, 14, 21, and 28]

    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.

  6. Number of Participants With the Indicated Gates Medical Research Institute (MRI) Scale Clinical Status at Days 8, 14, 21, and 28 [Days 8, 14, 21, and 28]

    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.

  7. Number of Participants With the Indicated World Health Organization (WHO) Ordinal Scale Clinical Status at Days 8, 14, 21, and 28 [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.

  8. Number of Participants With Hospitalization Through Days 8, 14, 21, and 28 [Days 8, 14, 21, and 28]

    Participants who had clinical worsening and who had at least one hospitalization during the study were analyzed.

  9. Median Number of Days of Hospitalization Through Day 35 [Up to Day 35]

    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.

  10. Shift in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28 [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. BS= Baseline; PBS= Post-Baseline; NA= Data not available.

  11. Shift in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28 [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. BS= Baseline; PBS= Post-Baseline; NA= Data not available.

Other Outcome Measures

  1. Change From Baseline in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28 [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.

  2. Change From Baseline in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Woodland Research Northwest LLC - ERG - PPDS Rogers Arkansas United States 72758
2 Science 37, Inc Los Angeles California United States 90094
3 Allergy and Asthma Medical Group and Research Center - CRN - PPDS San Diego California United States 92123
4 Invesclinic, LLC Fort Lauderdale Florida United States 33308
5 Advanced Pulmonary Research Institute Loxahatchee Groves Florida United States 33470
6 LCC Medical Research - Miami - BTC - PPDS Miami Florida United States 33126
7 Adult Medicine of Lake County Mount Dora Florida United States 32757
8 Providea Health Partners LLC Evergreen Park Illinois United States 60805
9 Clinical Research Institute, Inc - CRN - PPDS Minneapolis Minnesota United States 55402
10 Encompass Care North Las Vegas Nevada United States 89086
11 Riverside Medical Group - Circuit- PPDS Secaucus New Jersey United States 07094
12 NYC Health + Hospitals/Lincoln Bronx New York United States 10451
13 Elmhurst Hospital Center Elmhurst New York United States 11373
14 Harlem Hospital Center New York New York United States 10037
15 Premier Family Physicians - Austin - Hunt - PPDS Austin Texas United States 78735
16 Village Health Partners - Plano - Hunt - PPDS Plano Texas United States 75024
17 South Texas Allergy and Asthma Medical Professionals San Antonio Texas United States 78229
18 Boundary House Medical Centre Sale Cheshire United Kingdom M33 2RH
19 St Mary's Hospital - PPDS London City Of London United Kingdom W2 1NY
20 Royal Free Hospital London United Kingdom NW3 2Q

Sponsors and Collaborators

  • Bill & Melinda Gates Medical Research Institute

Investigators

  • Study Director: GatesMRI, Bill & Melinda Gates Medical Research Institute

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Bill & Melinda Gates Medical Research Institute
ClinicalTrials.gov Identifier:
NCT04504032
Other Study ID Numbers:
  • Gates MRI - COD-01-T01-01
  • 2020-005395-35
First Posted:
Aug 7, 2020
Last Update Posted:
Oct 22, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bill & Melinda Gates Medical Research Institute
Rivaroxaban
Xarelto
Coronavirus
COVID-19
Coronavirus disease 2019
Additional relevant MeSH terms:
COVID-19
Rivaroxaban

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail A total of 538 participants were screened of which only 497 were randomized to treatment.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Period Title: Overall Study
STARTED 246 251
COMPLETED 210 223
NOT COMPLETED 36 28

Baseline Characteristics

Arm/Group Title Rivaroxaban Placebo Total
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days. Total of all reporting groups
Overall Participants 246 251 497
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
49.8
(12.28)
48.6
(12.14)
49.2
(12.21)
Sex: Female, Male (Count of Participants)
Female
140
56.9%
159
63.3%
299
60.2%
Male
106
43.1%
92
36.7%
198
39.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
49
19.9%
46
18.3%
95
19.1%
Not Hispanic or Latino
197
80.1%
201
80.1%
398
80.1%
Unknown or Not Reported
0
0%
4
1.6%
4
0.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native
2
0.8%
2
0.8%
4
0.8%
Asian
0
0%
1
0.4%
1
0.2%
Black or African American
17
6.9%
19
7.6%
36
7.2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
White
219
89%
222
88.4%
441
88.7%
Mixed race
0
0%
0
0%
0
0%
Other
7
2.8%
7
2.8%
14
2.8%
Unknown
1
0.4%
0
0%
1
0.2%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35
Description 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.
Time Frame Up to Day 35

Outcome Measure Data

Analysis Population Description
Safety Population: all participants randomly assigned to study intervention, who received the study intervention. Participants were grouped according to the study intervention they actually received.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 219 230
Count of Participants [Participants]
6
2.4%
13
5.2%
2. Primary Outcome
Title Number of Participants With AEs Resulting in Study Intervention Discontinuation Through Day 35
Description 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.
Time Frame Up to Day 35

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 219 230
Count of Participants [Participants]
4
1.6%
5
2%
3. Primary Outcome
Title Number of Participants With Serious Adverse Events Through Day 35
Description 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.
Time Frame Up to Day 35

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 219 230
Count of Participants [Participants]
2
0.8%
7
2.8%
4. Primary Outcome
Title Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale Through Day 28
Description 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.
Time Frame Up to Day 28

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: All participants assigned to study intervention, who received the study intervention. Participants were grouped according to the study intervention to which they were randomized.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Count of Participants [Participants]
46
18.7%
44
17.5%
5. Secondary Outcome
Title Median Time to Disease Resolution Based on Symptoms Resolution Through Day 28
Description 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.
Time Frame Up to Day 28

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 132 122
Median (95% Confidence Interval) [Days]
21.0
23.0
6. Secondary Outcome
Title Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through Day 28
Description 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.
Time Frame Up to Day 28

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 125 115
Median (95% Confidence Interval) [Days]
23.0
26.0
7. Secondary Outcome
Title 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
Description 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.
Time Frame Days 8, 14, and 21

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Day 8
38
15.4%
36
14.3%
Day 14
44
17.9%
40
15.9%
Day 21
45
18.3%
42
16.7%
8. Secondary Outcome
Title Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at Days 8, 14, 21, and 28
Description 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.
Time Frame Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Day 8
26
10.6%
30
12%
Day 14
64
26%
59
23.5%
Day 21
100
40.7%
93
37.1%
Day 28
132
53.7%
122
48.6%
9. Secondary Outcome
Title Number of Participants Who Achieved Disease Resolution Based on Viral Clearance and Symptoms Resolution at Days 8, 14, 21, and 28
Description 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.
Time Frame Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Day 8
12
4.9%
20
8%
Day 14
49
19.9%
44
17.5%
Day 21
86
35%
83
33.1%
Day 28
125
50.8%
115
45.8%
10. Secondary Outcome
Title Number of Participants With the Indicated Gates Medical Research Institute (MRI) Scale Clinical Status at Days 8, 14, 21, and 28
Description 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.
Time Frame Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Score 1
33
13.4%
31
12.4%
Score 2
152
61.8%
159
63.3%
Score 3
3
1.2%
8
3.2%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 1
69
28%
55
21.9%
Score 2
114
46.3%
132
52.6%
Score 3
3
1.2%
7
2.8%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 1
98
39.8%
79
31.5%
Score 2
87
35.4%
109
43.4%
Score 3
1
0.4%
5
2%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 1
125
50.8%
108
43%
Score 2
57
23.2%
81
32.3%
Score 3
1
0.4%
4
1.6%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
11. Secondary Outcome
Title Number of Participants With the Indicated World Health Organization (WHO) Ordinal Scale Clinical Status at Days 8, 14, 21, and 28
Description 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.
Time Frame Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Score 0
19
7.7%
19
7.6%
Score 1
14
5.7%
12
4.8%
Score 2
154
62.6%
166
66.1%
Score 3
0
0%
1
0.4%
Score 4
1
0.4%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 8
0
0%
0
0%
Score 9
0
0%
0
0%
Score 10
0
0%
0
0%
Score 0
56
22.8%
40
15.9%
Score 1
15
6.1%
16
6.4%
Score 2
115
46.7%
137
54.6%
Score 3
0
0%
1
0.4%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 8
0
0%
0
0%
Score 9
0
0%
0
0%
Score 10
0
0%
0
0%
Score 0
87
35.4%
72
28.7%
Score 1
12
4.9%
8
3.2%
Score 2
87
35.4%
112
44.6%
Score 3
0
0%
1
0.4%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 8
0
0%
0
0%
Score 9
0
0%
0
0%
Score 10
0
0%
0
0%
Score 0
117
47.6%
106
42.2%
Score 1
9
3.7%
4
1.6%
Score 2
57
23.2%
82
32.7%
Score 3
0
0%
1
0.4%
Score 4
0
0%
0
0%
Score 5
0
0%
0
0%
Score 6
0
0%
0
0%
Score 7
0
0%
0
0%
Score 8
0
0%
0
0%
Score 9
0
0%
0
0%
Score 10
0
0%
0
0%
12. Secondary Outcome
Title Number of Participants With Hospitalization Through Days 8, 14, 21, and 28
Description Participants who had clinical worsening and who had at least one hospitalization during the study were analyzed.
Time Frame Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Up to Day 8
3
1.2%
6
2.4%
Up to Day 14
3
1.2%
7
2.8%
Up to Day 21
3
1.2%
7
2.8%
Up to Day 28
3
1.2%
7
2.8%
13. Secondary Outcome
Title Median Number of Days of Hospitalization Through Day 35
Description 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.
Time Frame Up to Day 35

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Median (Full Range) [Days]
5.0
4.0
14. Secondary Outcome
Title Shift in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
Description 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.
Time Frame Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Day 8: shift from BS score 1 to PBS score 1
2
0.8%
1
0.4%
Day 8: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score >=4
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score NA
0
0%
0
0%
Day 8: shift from BS score 2 to PBS score 1
31
12.6%
30
12%
Day 8: shift from BS score 2 to PBS score 2
152
61.8%
158
62.9%
Day 8: shift from BS score 2 to PBS score 3
3
1.2%
8
3.2%
Day 8: shift from BS score 2 to PBS score >=4
0
0%
0
0%
Day 8: shift from BS score 2 to PBS score NA
7
2.8%
4
1.6%
Day 8: shift from BS score 3 to PBS score 1
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score >=4
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score NA
12
4.9%
3
1.2%
Day 8: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 8: shift from BS score NA to PBS score >=4
0
0%
0
0%
Day 8: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
Day 14: shift from BS score 1 to PBS score 1
2
0.8%
1
0.4%
Day 14: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score >=4
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score NA
0
0%
0
0%
Day 14: shift from BS score 2 to PBS score 1
67
27.2%
54
21.5%
Day 14: shift from BS score 2 to PBS score 2
114
46.3%
131
52.2%
Day 14: shift from BS score 2 to PBS score 3
3
1.2%
7
2.8%
Day 14: shift from BS score 2 to PBS score >=4
0
0%
0
0%
Day 14: shift from BS score 2 to PBS score NA
9
3.7%
8
3.2%
Day 14: shift from BS score 3 to PBS score 1
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score 2
0
0%
1
0.4%
Day 14: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score >=4
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score NA
12
4.9%
3
1.2%
Day 14: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 14: shift from BS score NA to PBS score >=4
0
0%
0
0%
Day 14: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
Day 21: shift from BS score 1 to PBS score 1
2
0.8%
0
0%
Day 21: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score >=4
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score NA
0
0%
1
0.4%
Day 21: shift from BS score 2 to PBS score 1
96
39%
78
31.1%
Day 21: shift from BS score 2 to PBS score 2
87
35.4%
109
43.4%
Day 21: shift from BS score 2 to PBS score 3
1
0.4%
5
2%
Day 21: shift from BS score 2 to PBS score >=4
0
0%
0
0%
Day 21: shift from BS score 2 to PBS score NA
9
3.7%
8
3.2%
Day 21: shift from BS score 3 to PBS score 1
0
0%
1
0.4%
Day 21: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score >=4
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score NA
12
4.9%
3
1.2%
Day 21: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 21: shift from BS score NA to PBS score >=4
0
0%
0
0%
Day 21: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
Day 28: shift from BS score 1 to PBS score 1
2
0.8%
1
0.4%
Day 28: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score >=4
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score NA
0
0%
0
0%
Day 28: shift from BS score 2 to PBS score 1
123
50%
106
42.2%
Day 28: shift from BS score 2 to PBS score 2
57
23.2%
81
32.3%
Day 28: shift from BS score 2 to PBS score 3
1
0.4%
4
1.6%
Day 28: shift from BS score 2 to PBS score >=4
0
0%
0
0%
Day 28: shift from BS score 2 to PBS score NA
12
4.9%
9
3.6%
Day 28: shift from BS score 3 to PBS score 1
0
0%
1
0.4%
Day 28: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score >=4
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score NA
12
4.9%
3
1.2%
Day 28: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 28: shift from BS score NA to PBS score >=4
0
0%
0
0%
Day 28: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
15. Secondary Outcome
Title Shift in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
Description 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.
Time Frame Baseline; Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Measure Participants 222 222
Day 8: shift from BS score 0 to PBS score 0
2
0.8%
0
0%
Day 8: shift from BS score 0 to PBS score 1
0
0%
0
0%
Day 8: shift from BS score 0 to PBS score 2
0
0%
0
0%
Day 8: shift from BS score 0 to PBS score 3
0
0%
0
0%
Day 8: shift from BS score 0 to PBS score 4
0
0%
0
0%
Day 8: shift from BS score 0 to PBS score 5
0
0%
0
0%
Day 8: shift from BS score 0 to PBS score >=6
0
0%
0
0%
Day 8: shift from BS score 0 to PBS score NA
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score 0
0
0%
1
0.4%
Day 8: shift from BS score 1 to PBS score 1
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score 4
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score 5
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score >=6
0
0%
0
0%
Day 8: shift from BS score 1 to PBS score NA
0
0%
0
0%
Day 8: shift from BS score 2 to PBS score 0
17
6.9%
18
7.2%
Day 8: shift from BS score 2 to PBS score 1
14
5.7%
12
4.8%
Day 8: shift from BS score 2 to PBS score 2
154
62.6%
166
66.1%
Day 8: shift from BS score 2 to PBS score 3
0
0%
1
0.4%
Day 8: shift from BS score 2 to PBS score 4
1
0.4%
0
0%
Day 8: shift from BS score 2 to PBS score 5
0
0%
0
0%
Day 8: shift from BS score 2 to PBS score >=6
0
0%
0
0%
Day 8: shift from BS score 2 to PBS score NA
18
7.3%
7
2.8%
Day 8: shift from BS score 3 to PBS score 0
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 1
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 4
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score 5
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score >=6
0
0%
0
0%
Day 8: shift from BS score 3 to PBS score NA
1
0.4%
0
0%
Day 8: shift from BS score NA to PBS score 0
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 4
0
0%
0
0%
Day 8: shift from BS score NA to PBS score 5
0
0%
0
0%
Day 8: shift from BS score NA to PBS score >=6
0
0%
0
0%
Day 8: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
Day 14: shift from BS score 0 to PBS score 0
2
0.8%
0
0%
Day 14: shift from BS score 0 to PBS score 1
0
0%
0
0%
Day 14: shift from BS score 0 to PBS score 2
0
0%
0
0%
Day 14: shift from BS score 0 to PBS score 3
0
0%
0
0%
Day 14: shift from BS score 0 to PBS score 4
0
0%
0
0%
Day 14: shift from BS score 0 to PBS score 5
0
0%
0
0%
Day 14: shift from BS score 0 to PBS score >=6
0
0%
0
0%
Day 14: shift from BS score 0 to PBS score NA
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score 0
0
0%
1
0.4%
Day 14: shift from BS score 1 to PBS score 1
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score 4
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score 5
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score >=6
0
0%
0
0%
Day 14: shift from BS score 1 to PBS score NA
0
0%
0
0%
Day 14: shift from BS score 2 to PBS score 0
54
22%
39
15.5%
Day 14: shift from BS score 2 to PBS score 1
15
6.1%
16
6.4%
Day 14: shift from BS score 2 to PBS score 2
115
46.7%
137
54.6%
Day 14: shift from BS score 2 to PBS score 3
0
0%
1
0.4%
Day 14: shift from BS score 2 to PBS score 4
0
0%
0
0%
Day 14: shift from BS score 2 to PBS score 5
0
0%
0
0%
Day 14: shift from BS score 2 to PBS score >=6
0
0%
0
0%
Day 14: shift from BS score 2 to PBS score NA
20
8.1%
11
4.4%
Day 14: shift from BS score 3 to PBS score 0
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score 1
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score 4
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score 5
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score >=6
0
0%
0
0%
Day 14: shift from BS score 3 to PBS score NA
1
0.4%
0
0%
Day 14: shift from BS score NA to PBS score 0
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 4
0
0%
0
0%
Day 14: shift from BS score NA to PBS score 5
0
0%
0
0%
Day 14: shift from BS score NA to PBS score >=6
0
0%
0
0%
Day 14: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
Day 21: shift from BS score 0 to PBS score 0
2
0.8%
0
0%
Day 21: shift from BS score 0 to PBS score 1
0
0%
0
0%
Day 21: shift from BS score 0 to PBS score 2
0
0%
0
0%
Day 21: shift from BS score 0 to PBS score 3
0
0%
0
0%
Day 21: shift from BS score 0 to PBS score 4
0
0%
0
0%
Day 21: shift from BS score 0 to PBS score 5
0
0%
0
0%
Day 21: shift from BS score 0 to PBS score >=6
0
0%
0
0%
Day 21: shift from BS score 0 to PBS score NA
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 0
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 1
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 4
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score 5
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score >=6
0
0%
0
0%
Day 21: shift from BS score 1 to PBS score NA
0
0%
1
0.4%
Day 21: shift from BS score 2 to PBS score 0
85
34.6%
72
28.7%
Day 21: shift from BS score 2 to PBS score 1
12
4.9%
8
3.2%
Day 21: shift from BS score 2 to PBS score 2
87
35.4%
112
44.6%
Day 21: shift from BS score 2 to PBS score 3
0
0%
1
0.4%
Day 21: shift from BS score 2 to PBS score 4
0
0%
0
0%
Day 21: shift from BS score 2 to PBS score 5
0
0%
0
0%
Day 21: shift from BS score 2 to PBS score >=6
0
0%
0
0%
Day 21: shift from BS score 2 to PBS score NA
20
8.1%
11
4.4%
Day 21: shift from BS score 3 to PBS score 0
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score 1
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score 4
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score 5
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score >=6
0
0%
0
0%
Day 21: shift from BS score 3 to PBS score NA
1
0.4%
0
0%
Day 21: shift from BS score NA to PBS score 0
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 4
0
0%
0
0%
Day 21: shift from BS score NA to PBS score 5
0
0%
0
0%
Day 21: shift from BS score NA to PBS score >=6
0
0%
0
0%
Day 21: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
Day 28: shift from BS score 0 to PBS score 0
2
0.8%
0
0%
Day 28: shift from BS score 0 to PBS score 1
0
0%
0
0%
Day 28: shift from BS score 0 to PBS score 2
0
0%
0
0%
Day 28: shift from BS score 0 to PBS score 3
0
0%
0
0%
Day 28: shift from BS score 0 to PBS score 4
0
0%
0
0%
Day 28: shift from BS score 0 to PBS score 5
0
0%
0
0%
Day 28: shift from BS score 0 to PBS score >=6
0
0%
0
0%
Day 28: shift from BS score 0 to PBS score NA
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score 0
0
0%
1
0.4%
Day 28: shift from BS score 1 to PBS score 1
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score 2
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score 3
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score 4
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score 5
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score >=6
0
0%
0
0%
Day 28: shift from BS score 1 to PBS score NA
0
0%
0
0%
Day 28: shift from BS score 2 to PBS score 0
115
46.7%
105
41.8%
Day 28: shift from BS score 2 to PBS score 1
9
3.7%
4
1.6%
Day 28: shift from BS score 2 to PBS score 2
57
23.2%
82
32.7%
Day 28: shift from BS score 2 to PBS score 3
0
0%
1
0.4%
Day 28: shift from BS score 2 to PBS score 4
0
0%
0
0%
Day 28: shift from BS score 2 to PBS score 5
0
0%
0
0%
Day 28: shift from BS score 2 to PBS score >=6
0
0%
0
0%
Day 28: shift from BS score 2 to PBS score NA
23
9.3%
12
4.8%
Day 28: shift from BS score 3 to PBS score 0
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score 1
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score 2
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score 3
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score 4
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score 5
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score >=6
0
0%
0
0%
Day 28: shift from BS score 3 to PBS score NA
1
0.4%
0
0%
Day 28: shift from BS score NA to PBS score 0
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 1
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 2
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 3
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 4
0
0%
0
0%
Day 28: shift from BS score NA to PBS score 5
0
0%
0
0%
Day 28: shift from BS score NA to PBS score >=6
0
0%
0
0%
Day 28: shift from BS score NA to PBS score NA
15
6.1%
17
6.8%
16. Other Pre-specified Outcome
Title Change From Baseline in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
Description 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.
Time Frame Baseline; Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
17. Other Pre-specified Outcome
Title Change From Baseline in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
Description 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.
Time Frame Baseline; Days 8, 14, 21, and 28

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description

Adverse Events

Time Frame Adverse events were collected from the time of consent up to 14 days after the last dose of study treatment (Day 35).
Adverse Event Reporting Description Analysis was performed in the Safety Population, comprised of all participants randomly assigned to study intervention, who received the study intervention. Participants were grouped according to the study intervention they actually received.
Arm/Group Title Rivaroxaban Placebo
Arm/Group Description Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days. Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
All Cause Mortality
Rivaroxaban Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/219 (0%) 0/230 (0%)
Serious Adverse Events
Rivaroxaban Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/219 (0.9%) 7/230 (3%)
Gastrointestinal disorders
Pancreatitis 0/219 (0%) 0 1/230 (0.4%) 1
Infections and infestations
COVID-19 pneumonia 2/219 (0.9%) 2 4/230 (1.7%) 4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injury 0/219 (0%) 0 1/230 (0.4%) 1
Vascular disorders
Deep vein thrombosis 0/219 (0%) 0 1/230 (0.4%) 1
Malignant hypertension 0/219 (0%) 0 1/230 (0.4%) 1
Other (Not Including Serious) Adverse Events
Rivaroxaban Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 12/219 (5.5%) 11/230 (4.8%)
Infections and infestations
Urinary Tract Infection 4/219 (1.8%) 4 0/230 (0%) 0
COVID -19/COVID-19 pneumonia/pneumonia 1/219 (0.5%) 1 5/230 (2.2%) 5
Nervous system disorders
Headache 3/219 (1.4%) 3 4/230 (1.7%) 4
Renal and urinary disorders
Hematuria 3/219 (1.4%) 3 0/230 (0%) 0
Respiratory, thoracic and mediastinal disorders
Dyspnea 1/219 (0.5%) 1 3/230 (1.3%) 3

Limitations/Caveats

Based on Data Monitoring Committee's recommendation on 3 February 2021, the study was stopped on 4 February 2021 due to futility.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results Point of Contact

Name/Title Study Director
Organization Gates MRI
Phone +1 857 702 2108
Email clinical.trials@gatesmri.org
Responsible Party:
Bill & Melinda Gates Medical Research Institute
ClinicalTrials.gov Identifier:
NCT04504032
Other Study ID Numbers:
  • Gates MRI - COD-01-T01-01
  • 2020-005395-35
First Posted:
Aug 7, 2020
Last Update Posted:
Oct 22, 2021
Last Verified:
Oct 1, 2021