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

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ClinicalTrials.gov Identifier: NCT04504032
Recruitment Status : Terminated (Based on Data Monitoring Committee''s recommendation on 3 February 2021, the study was stopped on 4 February 2021 due to futility.)
First Posted : August 7, 2020
Results First Posted : October 22, 2021
Last Update Posted : October 22, 2021
Sponsor:
Information provided by (Responsible Party):
Bill & Melinda Gates Medical Research Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition COVID-19
Interventions Drug: Rivaroxaban
Drug: Placebo
Enrollment 497
Recruitment Details  
Pre-assignment Details A total of 538 participants were screened of which only 497 were randomized to treatment.
Arm/Group Title Rivaroxaban Placebo
Hide 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
Reason Not Completed
Adverse Event             1             2
Lost to Follow-up             6             9
Protocol Violation             2             0
Study terminated by sponsor             1             2
Withdrawal by Subject             9             11
Disease progression prior to dosing             15             3
Drug supply issues             1             1
Progressed to moderate/severe COVID-19             1             0
Arm/Group Title Rivaroxaban Placebo Total
Hide 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 Number of Baseline Participants 246 251 497
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 246 participants 251 participants 497 participants
49.8  (12.28) 48.6  (12.14) 49.2  (12.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 251 participants 497 participants
Female
140
  56.9%
159
  63.3%
299
  60.2%
Male
106
  43.1%
92
  36.7%
198
  39.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 251 participants 497 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
   0.0%
4
   1.6%
4
   0.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 251 participants 497 participants
American Indian or Alaska Native
2
   0.8%
2
   0.8%
4
   0.8%
Asian
0
   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%
0
   0.0%
White
219
  89.0%
222
  88.4%
441
  88.7%
Mixed race
0
   0.0%
0
   0.0%
0
   0.0%
Other
7
   2.8%
7
   2.8%
14
   2.8%
Unknown
1
   0.4%
0
   0.0%
1
   0.2%
1.Primary Outcome
Title Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 219 230
Measure Type: Count of Participants
Unit of Measure: Participants
6
   2.7%
13
   5.7%
2.Primary Outcome
Title Number of Participants With AEs Resulting in Study Intervention Discontinuation Through Day 35
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 219 230
Measure Type: Count of Participants
Unit of Measure: Participants
4
   1.8%
5
   2.2%
3.Primary Outcome
Title Number of Participants With Serious Adverse Events Through Day 35
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 219 230
Measure Type: Count of Participants
Unit of Measure: Participants
2
   0.9%
7
   3.0%
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
46
  20.7%
44
  19.8%
5.Secondary Outcome
Title Median Time to Disease Resolution Based on Symptoms Resolution Through Day 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 132 122
Median (95% Confidence Interval)
Unit of Measure: Days
21.0
(19.0 to 23.0)
23.0
(20.0 to 27.0)
6.Secondary Outcome
Title Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through Day 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 125 115
Median (95% Confidence Interval)
Unit of Measure: Days
23.0
(21.0 to 26.0)
26.0
(22.0 to 28.0)
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
Day 8
38
  17.1%
36
  16.2%
Day 14
44
  19.8%
40
  18.0%
Day 21
45
  20.3%
42
  18.9%
8.Secondary Outcome
Title Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at Days 8, 14, 21, and 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
Day 8
26
  11.7%
30
  13.5%
Day 14
64
  28.8%
59
  26.6%
Day 21
100
  45.0%
93
  41.9%
Day 28
132
  59.5%
122
  55.0%
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
Day 8
12
   5.4%
20
   9.0%
Day 14
49
  22.1%
44
  19.8%
Day 21
86
  38.7%
83
  37.4%
Day 28
125
  56.3%
115
  51.8%
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
Day 8 Number Analyzed 188 participants 198 participants
Score 1
33
  17.6%
31
  15.7%
Score 2
152
  80.9%
159
  80.3%
Score 3
3
   1.6%
8
   4.0%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Day 14 Number Analyzed 186 participants 194 participants
Score 1
69
  37.1%
55
  28.4%
Score 2
114
  61.3%
132
  68.0%
Score 3
3
   1.6%
7
   3.6%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Day 21 Number Analyzed 186 participants 193 participants
Score 1
98
  52.7%
79
  40.9%
Score 2
87
  46.8%
109
  56.5%
Score 3
1
   0.5%
5
   2.6%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Day 28 Number Analyzed 183 participants 193 participants
Score 1
125
  68.3%
108
  56.0%
Score 2
57
  31.1%
81
  42.0%
Score 3
1
   0.5%
4
   2.1%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data were analyzed.
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
Day 8 Number Analyzed 188 participants 198 participants
Score 0
19
  10.1%
19
   9.6%
Score 1
14
   7.4%
12
   6.1%
Score 2
154
  81.9%
166
  83.8%
Score 3
0
   0.0%
1
   0.5%
Score 4
1
   0.5%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Score 8
0
   0.0%
0
   0.0%
Score 9
0
   0.0%
0
   0.0%
Score 10
0
   0.0%
0
   0.0%
Day 14 Number Analyzed 186 participants 194 participants
Score 0
56
  30.1%
40
  20.6%
Score 1
15
   8.1%
16
   8.2%
Score 2
115
  61.8%
137
  70.6%
Score 3
0
   0.0%
1
   0.5%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Score 8
0
   0.0%
0
   0.0%
Score 9
0
   0.0%
0
   0.0%
Score 10
0
   0.0%
0
   0.0%
Day 21 Number Analyzed 186 participants 193 participants
Score 0
87
  46.8%
72
  37.3%
Score 1
12
   6.5%
8
   4.1%
Score 2
87
  46.8%
112
  58.0%
Score 3
0
   0.0%
1
   0.5%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Score 8
0
   0.0%
0
   0.0%
Score 9
0
   0.0%
0
   0.0%
Score 10
0
   0.0%
0
   0.0%
Day 28 Number Analyzed 183 participants 193 participants
Score 0
117
  63.9%
106
  54.9%
Score 1
9
   4.9%
4
   2.1%
Score 2
57
  31.1%
82
  42.5%
Score 3
0
   0.0%
1
   0.5%
Score 4
0
   0.0%
0
   0.0%
Score 5
0
   0.0%
0
   0.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
0
   0.0%
0
   0.0%
Score 8
0
   0.0%
0
   0.0%
Score 9
0
   0.0%
0
   0.0%
Score 10
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Number of Participants With Hospitalization Through Days 8, 14, 21, and 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Count of Participants
Unit of Measure: Participants
Up to Day 8
3
   1.4%
6
   2.7%
Up to Day 14
3
   1.4%
7
   3.2%
Up to Day 21
3
   1.4%
7
   3.2%
Up to Day 28
3
   1.4%
7
   3.2%
13.Secondary Outcome
Title Median Number of Days of Hospitalization Through Day 35
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Median (Full Range)
Unit of Measure: Days
5.0
(4.0 to 5.0)
4.0
(2.0 to 30.0)
14.Secondary Outcome
Title Shift in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Number
Unit of Measure: Participants
Day 8: shift from BS score 1 to PBS score 1 2 1
Day 8: shift from BS score 1 to PBS score 2 0 0
Day 8: shift from BS score 1 to PBS score 3 0 0
Day 8: shift from BS score 1 to PBS score >=4 0 0
Day 8: shift from BS score 1 to PBS score NA 0 0
Day 8: shift from BS score 2 to PBS score 1 31 30
Day 8: shift from BS score 2 to PBS score 2 152 158
Day 8: shift from BS score 2 to PBS score 3 3 8
Day 8: shift from BS score 2 to PBS score >=4 0 0
Day 8: shift from BS score 2 to PBS score NA 7 4
Day 8: shift from BS score 3 to PBS score 1 0 0
Day 8: shift from BS score 3 to PBS score 2 0 0
Day 8: shift from BS score 3 to PBS score 3 0 0
Day 8: shift from BS score 3 to PBS score >=4 0 0
Day 8: shift from BS score 3 to PBS score NA 12 3
Day 8: shift from BS score NA to PBS score 1 0 0
Day 8: shift from BS score NA to PBS score 2 0 0
Day 8: shift from BS score NA to PBS score 3 0 0
Day 8: shift from BS score NA to PBS score >=4 0 0
Day 8: shift from BS score NA to PBS score NA 15 17
Day 14: shift from BS score 1 to PBS score 1 2 1
Day 14: shift from BS score 1 to PBS score 2 0 0
Day 14: shift from BS score 1 to PBS score 3 0 0
Day 14: shift from BS score 1 to PBS score >=4 0 0
Day 14: shift from BS score 1 to PBS score NA 0 0
Day 14: shift from BS score 2 to PBS score 1 67 54
Day 14: shift from BS score 2 to PBS score 2 114 131
Day 14: shift from BS score 2 to PBS score 3 3 7
Day 14: shift from BS score 2 to PBS score >=4 0 0
Day 14: shift from BS score 2 to PBS score NA 9 8
Day 14: shift from BS score 3 to PBS score 1 0 0
Day 14: shift from BS score 3 to PBS score 2 0 1
Day 14: shift from BS score 3 to PBS score 3 0 0
Day 14: shift from BS score 3 to PBS score >=4 0 0
Day 14: shift from BS score 3 to PBS score NA 12 3
Day 14: shift from BS score NA to PBS score 1 0 0
Day 14: shift from BS score NA to PBS score 2 0 0
Day 14: shift from BS score NA to PBS score 3 0 0
Day 14: shift from BS score NA to PBS score >=4 0 0
Day 14: shift from BS score NA to PBS score NA 15 17
Day 21: shift from BS score 1 to PBS score 1 2 0
Day 21: shift from BS score 1 to PBS score 2 0 0
Day 21: shift from BS score 1 to PBS score 3 0 0
Day 21: shift from BS score 1 to PBS score >=4 0 0
Day 21: shift from BS score 1 to PBS score NA 0 1
Day 21: shift from BS score 2 to PBS score 1 96 78
Day 21: shift from BS score 2 to PBS score 2 87 109
Day 21: shift from BS score 2 to PBS score 3 1 5
Day 21: shift from BS score 2 to PBS score >=4 0 0
Day 21: shift from BS score 2 to PBS score NA 9 8
Day 21: shift from BS score 3 to PBS score 1 0 1
Day 21: shift from BS score 3 to PBS score 2 0 0
Day 21: shift from BS score 3 to PBS score 3 0 0
Day 21: shift from BS score 3 to PBS score >=4 0 0
Day 21: shift from BS score 3 to PBS score NA 12 3
Day 21: shift from BS score NA to PBS score 1 0 0
Day 21: shift from BS score NA to PBS score 2 0 0
Day 21: shift from BS score NA to PBS score 3 0 0
Day 21: shift from BS score NA to PBS score >=4 0 0
Day 21: shift from BS score NA to PBS score NA 15 17
Day 28: shift from BS score 1 to PBS score 1 2 1
Day 28: shift from BS score 1 to PBS score 2 0 0
Day 28: shift from BS score 1 to PBS score 3 0 0
Day 28: shift from BS score 1 to PBS score >=4 0 0
Day 28: shift from BS score 1 to PBS score NA 0 0
Day 28: shift from BS score 2 to PBS score 1 123 106
Day 28: shift from BS score 2 to PBS score 2 57 81
Day 28: shift from BS score 2 to PBS score 3 1 4
Day 28: shift from BS score 2 to PBS score >=4 0 0
Day 28: shift from BS score 2 to PBS score NA 12 9
Day 28: shift from BS score 3 to PBS score 1 0 1
Day 28: shift from BS score 3 to PBS score 2 0 0
Day 28: shift from BS score 3 to PBS score 3 0 0
Day 28: shift from BS score 3 to PBS score >=4 0 0
Day 28: shift from BS score 3 to PBS score NA 12 3
Day 28: shift from BS score NA to PBS score 1 0 0
Day 28: shift from BS score NA to PBS score 2 0 0
Day 28: shift from BS score NA to PBS score 3 0 0
Day 28: shift from BS score NA to PBS score >=4 0 0
Day 28: shift from BS score NA to PBS score NA 15 17
15.Secondary Outcome
Title Shift in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Rivaroxaban Placebo
Hide 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.
Overall Number of Participants Analyzed 222 222
Measure Type: Number
Unit of Measure: Participants
Day 8: shift from BS score 0 to PBS score 0 2 0
Day 8: shift from BS score 0 to PBS score 1 0 0
Day 8: shift from BS score 0 to PBS score 2 0 0
Day 8: shift from BS score 0 to PBS score 3 0 0
Day 8: shift from BS score 0 to PBS score 4 0 0
Day 8: shift from BS score 0 to PBS score 5 0 0
Day 8: shift from BS score 0 to PBS score >=6 0 0
Day 8: shift from BS score 0 to PBS score NA 0 0
Day 8: shift from BS score 1 to PBS score 0 0 1
Day 8: shift from BS score 1 to PBS score 1 0 0
Day 8: shift from BS score 1 to PBS score 2 0 0
Day 8: shift from BS score 1 to PBS score 3 0 0
Day 8: shift from BS score 1 to PBS score 4 0 0
Day 8: shift from BS score 1 to PBS score 5 0 0
Day 8: shift from BS score 1 to PBS score >=6 0 0
Day 8: shift from BS score 1 to PBS score NA 0 0
Day 8: shift from BS score 2 to PBS score 0 17 18
Day 8: shift from BS score 2 to PBS score 1 14 12
Day 8: shift from BS score 2 to PBS score 2 154 166
Day 8: shift from BS score 2 to PBS score 3 0 1
Day 8: shift from BS score 2 to PBS score 4 1 0
Day 8: shift from BS score 2 to PBS score 5 0 0
Day 8: shift from BS score 2 to PBS score >=6 0 0
Day 8: shift from BS score 2 to PBS score NA 18 7
Day 8: shift from BS score 3 to PBS score 0 0 0
Day 8: shift from BS score 3 to PBS score 1 0 0
Day 8: shift from BS score 3 to PBS score 2 0 0
Day 8: shift from BS score 3 to PBS score 3 0 0
Day 8: shift from BS score 3 to PBS score 4 0 0
Day 8: shift from BS score 3 to PBS score 5 0 0
Day 8: shift from BS score 3 to PBS score >=6 0 0
Day 8: shift from BS score 3 to PBS score NA 1 0
Day 8: shift from BS score NA to PBS score 0 0 0
Day 8: shift from BS score NA to PBS score 1 0 0
Day 8: shift from BS score NA to PBS score 2 0 0
Day 8: shift from BS score NA to PBS score 3 0 0
Day 8: shift from BS score NA to PBS score 4 0 0
Day 8: shift from BS score NA to PBS score 5 0 0
Day 8: shift from BS score NA to PBS score >=6 0 0
Day 8: shift from BS score NA to PBS score NA 15 17
Day 14: shift from BS score 0 to PBS score 0 2 0
Day 14: shift from BS score 0 to PBS score 1 0 0
Day 14: shift from BS score 0 to PBS score 2 0 0
Day 14: shift from BS score 0 to PBS score 3 0 0
Day 14: shift from BS score 0 to PBS score 4 0 0
Day 14: shift from BS score 0 to PBS score 5 0 0
Day 14: shift from BS score 0 to PBS score >=6 0 0
Day 14: shift from BS score 0 to PBS score NA 0 0
Day 14: shift from BS score 1 to PBS score 0 0 1
Day 14: shift from BS score 1 to PBS score 1 0 0
Day 14: shift from BS score 1 to PBS score 2 0 0
Day 14: shift from BS score 1 to PBS score 3 0 0
Day 14: shift from BS score 1 to PBS score 4 0 0
Day 14: shift from BS score 1 to PBS score 5 0 0
Day 14: shift from BS score 1 to PBS score >=6 0 0
Day 14: shift from BS score 1 to PBS score NA 0 0
Day 14: shift from BS score 2 to PBS score 0 54 39
Day 14: shift from BS score 2 to PBS score 1 15 16
Day 14: shift from BS score 2 to PBS score 2 115 137
Day 14: shift from BS score 2 to PBS score 3 0 1
Day 14: shift from BS score 2 to PBS score 4 0 0
Day 14: shift from BS score 2 to PBS score 5 0 0
Day 14: shift from BS score 2 to PBS score >=6 0 0
Day 14: shift from BS score 2 to PBS score NA 20 11
Day 14: shift from BS score 3 to PBS score 0 0 0
Day 14: shift from BS score 3 to PBS score 1 0 0
Day 14: shift from BS score 3 to PBS score 2 0 0
Day 14: shift from BS score 3 to PBS score 3 0 0
Day 14: shift from BS score 3 to PBS score 4 0 0
Day 14: shift from BS score 3 to PBS score 5 0 0
Day 14: shift from BS score 3 to PBS score >=6 0 0
Day 14: shift from BS score 3 to PBS score NA 1 0
Day 14: shift from BS score NA to PBS score 0 0 0
Day 14: shift from BS score NA to PBS score 1 0 0
Day 14: shift from BS score NA to PBS score 2 0 0
Day 14: shift from BS score NA to PBS score 3 0 0
Day 14: shift from BS score NA to PBS score 4 0 0
Day 14: shift from BS score NA to PBS score 5 0 0
Day 14: shift from BS score NA to PBS score >=6 0 0
Day 14: shift from BS score NA to PBS score NA 15 17
Day 21: shift from BS score 0 to PBS score 0 2 0
Day 21: shift from BS score 0 to PBS score 1 0 0
Day 21: shift from BS score 0 to PBS score 2 0 0
Day 21: shift from BS score 0 to PBS score 3 0 0
Day 21: shift from BS score 0 to PBS score 4 0 0
Day 21: shift from BS score 0 to PBS score 5 0 0
Day 21: shift from BS score 0 to PBS score >=6 0 0
Day 21: shift from BS score 0 to PBS score NA 0 0
Day 21: shift from BS score 1 to PBS score 0 0 0
Day 21: shift from BS score 1 to PBS score 1 0 0
Day 21: shift from BS score 1 to PBS score 2 0 0
Day 21: shift from BS score 1 to PBS score 3 0 0
Day 21: shift from BS score 1 to PBS score 4 0 0
Day 21: shift from BS score 1 to PBS score 5 0 0
Day 21: shift from BS score 1 to PBS score >=6 0 0
Day 21: shift from BS score 1 to PBS score NA 0 1
Day 21: shift from BS score 2 to PBS score 0 85 72
Day 21: shift from BS score 2 to PBS score 1 12 8
Day 21: shift from BS score 2 to PBS score 2 87 112
Day 21: shift from BS score 2 to PBS score 3 0 1
Day 21: shift from BS score 2 to PBS score 4 0 0
Day 21: shift from BS score 2 to PBS score 5 0 0
Day 21: shift from BS score 2 to PBS score >=6 0 0
Day 21: shift from BS score 2 to PBS score NA 20 11
Day 21: shift from BS score 3 to PBS score 0 0 0
Day 21: shift from BS score 3 to PBS score 1 0 0
Day 21: shift from BS score 3 to PBS score 2 0 0
Day 21: shift from BS score 3 to PBS score 3 0 0
Day 21: shift from BS score 3 to PBS score 4 0 0
Day 21: shift from BS score 3 to PBS score 5 0 0
Day 21: shift from BS score 3 to PBS score >=6 0 0
Day 21: shift from BS score 3 to PBS score NA 1 0
Day 21: shift from BS score NA to PBS score 0 0 0
Day 21: shift from BS score NA to PBS score 1 0 0
Day 21: shift from BS score NA to PBS score 2 0 0
Day 21: shift from BS score NA to PBS score 3 0 0
Day 21: shift from BS score NA to PBS score 4 0 0
Day 21: shift from BS score NA to PBS score 5 0 0
Day 21: shift from BS score NA to PBS score >=6 0 0
Day 21: shift from BS score NA to PBS score NA 15 17
Day 28: shift from BS score 0 to PBS score 0 2 0
Day 28: shift from BS score 0 to PBS score 1 0 0
Day 28: shift from BS score 0 to PBS score 2 0 0
Day 28: shift from BS score 0 to PBS score 3 0 0
Day 28: shift from BS score 0 to PBS score 4 0 0
Day 28: shift from BS score 0 to PBS score 5 0 0
Day 28: shift from BS score 0 to PBS score >=6 0 0
Day 28: shift from BS score 0 to PBS score NA 0 0
Day 28: shift from BS score 1 to PBS score 0 0 1
Day 28: shift from BS score 1 to PBS score 1 0 0
Day 28: shift from BS score 1 to PBS score 2 0 0
Day 28: shift from BS score 1 to PBS score 3 0 0
Day 28: shift from BS score 1 to PBS score 4 0 0
Day 28: shift from BS score 1 to PBS score 5 0 0
Day 28: shift from BS score 1 to PBS score >=6 0 0
Day 28: shift from BS score 1 to PBS score NA 0 0
Day 28: shift from BS score 2 to PBS score 0 115 105
Day 28: shift from BS score 2 to PBS score 1 9 4
Day 28: shift from BS score 2 to PBS score 2 57 82
Day 28: shift from BS score 2 to PBS score 3 0 1
Day 28: shift from BS score 2 to PBS score 4 0 0
Day 28: shift from BS score 2 to PBS score 5 0 0
Day 28: shift from BS score 2 to PBS score >=6 0 0
Day 28: shift from BS score 2 to PBS score NA 23 12
Day 28: shift from BS score 3 to PBS score 0 0 0
Day 28: shift from BS score 3 to PBS score 1 0 0
Day 28: shift from BS score 3 to PBS score 2 0 0
Day 28: shift from BS score 3 to PBS score 3 0 0
Day 28: shift from BS score 3 to PBS score 4 0 0
Day 28: shift from BS score 3 to PBS score 5 0 0
Day 28: shift from BS score 3 to PBS score >=6 0 0
Day 28: shift from BS score 3 to PBS score NA 1 0
Day 28: shift from BS score NA to PBS score 0 0 0
Day 28: shift from BS score NA to PBS score 1 0 0
Day 28: shift from BS score NA to PBS score 2 0 0
Day 28: shift from BS score NA to PBS score 3 0 0
Day 28: shift from BS score NA to PBS score 4 0 0
Day 28: shift from BS score NA to PBS score 5 0 0
Day 28: shift from BS score NA to PBS score >=6 0 0
Day 28: shift from BS score NA to PBS score NA 15 17
16.Other Pre-specified Outcome
Title Change From Baseline in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
Hide 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 Not Reported
17.Other Pre-specified Outcome
Title Change From Baseline in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
Hide 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 Not Reported
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
Hide 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 (%) Affected / at Risk (%)
Total   0/219 (0.00%)      0/230 (0.00%)    
Hide Serious Adverse Events
Rivaroxaban Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/219 (0.91%)      7/230 (3.04%)    
Gastrointestinal disorders     
Pancreatitis  1  0/219 (0.00%)  0 1/230 (0.43%)  1
Infections and infestations     
COVID-19 pneumonia  1  2/219 (0.91%)  2 4/230 (1.74%)  4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute kidney injury  1  0/219 (0.00%)  0 1/230 (0.43%)  1
Vascular disorders     
Deep vein thrombosis  1  0/219 (0.00%)  0 1/230 (0.43%)  1
Malignant hypertension  1  0/219 (0.00%)  0 1/230 (0.43%)  1
1
Term from vocabulary, MedDra 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Rivaroxaban Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/219 (5.48%)      11/230 (4.78%)    
Infections and infestations     
Urinary Tract Infection  1  4/219 (1.83%)  4 0/230 (0.00%)  0
COVID -19/COVID-19 pneumonia/pneumonia  1  1/219 (0.46%)  1 5/230 (2.17%)  5
Nervous system disorders     
Headache  1  3/219 (1.37%)  3 4/230 (1.74%)  4
Renal and urinary disorders     
Hematuria  1  3/219 (1.37%)  3 0/230 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  1/219 (0.46%)  1 3/230 (1.30%)  3
1
Term from vocabulary, MedDra 23.0
Indicates events were collected by systematic assessment
Based on Data Monitoring Committee's recommendation on 3 February 2021, the study was stopped on 4 February 2021 due to futility.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Gates MRI
Phone: +1 857 702 2108
EMail: clinical.trials@gatesmri.org
Layout table for additonal information
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 ( EudraCT Number )
First Submitted: August 5, 2020
First Posted: August 7, 2020
Results First Submitted: September 29, 2021
Results First Posted: October 22, 2021
Last Update Posted: October 22, 2021