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

Primary Purpose

COVID-19

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rivaroxaban
Placebo
Sponsored by
Bill & Melinda Gates Medical Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Rivaroxaban, Xarelto, Coronavirus, COVID-19, Coronavirus disease 2019

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Woodland Research Northwest LLC - ERG - PPDS
  • Science 37, Inc
  • Allergy and Asthma Medical Group and Research Center - CRN - PPDS
  • Invesclinic, LLC
  • Advanced Pulmonary Research Institute
  • LCC Medical Research - Miami - BTC - PPDS
  • Adult Medicine of Lake County
  • Providea Health Partners LLC
  • Clinical Research Institute, Inc - CRN - PPDS
  • Encompass Care
  • Riverside Medical Group - Circuit- PPDS
  • NYC Health + Hospitals/Lincoln
  • Elmhurst Hospital Center
  • Harlem Hospital Center
  • Premier Family Physicians - Austin - Hunt - PPDS
  • Village Health Partners - Plano - Hunt - PPDS
  • South Texas Allergy and Asthma Medical Professionals
  • Boundary House Medical Centre
  • St Mary's Hospital - PPDS
  • Royal Free Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rivaroxaban

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through 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.
Number of Participants With AEs Resulting in Study Intervention Discontinuation Through 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.
Number of Participants With Serious Adverse Events Through 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.
Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale Through 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

Median Time to Disease Resolution Based on Symptoms Resolution Through 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.
Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through 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.
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
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.
Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at 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.
Number of Participants Who Achieved Disease Resolution Based on Viral Clearance and Symptoms Resolution at 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.
Number of Participants With the Indicated Gates Medical Research Institute (MRI) Scale Clinical Status at 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.
Number of Participants With the Indicated World Health Organization (WHO) Ordinal Scale Clinical Status at 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.
Number of Participants With Hospitalization Through Days 8, 14, 21, and 28
Participants who had clinical worsening and who had at least one hospitalization during the study were analyzed.
Median Number of Days of Hospitalization Through 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.
Shift in Gates Medical Research Institute Ordinal Scale Score at 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.
Shift in World Health Organization Ordinal Scale Score at 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.

Full Information

First Posted
August 5, 2020
Last Updated
October 20, 2021
Sponsor
Bill & Melinda Gates Medical Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04504032
Brief Title
A Trial to Evaluate Safety and Efficacy of Rivaroxaban (COVID-19)
Official Title
A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Based on Data Monitoring Committee''s recommendation on 3 February 2021, the study was stopped on 4 February 2021 due to futility.
Study Start Date
September 2, 2020 (Actual)
Primary Completion Date
March 10, 2021 (Actual)
Study Completion Date
March 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bill & Melinda Gates Medical Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Rivaroxaban, Xarelto, Coronavirus, COVID-19, Coronavirus disease 2019

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
497 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rivaroxaban
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Intervention Description
Participants self-administered rivaroxaban, 10 milligrams (mg) (1 tablet) orally once daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.
Primary Outcome Measure Information:
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
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
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
Other Pre-specified Outcome Measures:
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GatesMRI
Organizational Affiliation
Bill & Melinda Gates Medical Research Institute
Official's Role
Study Director
Facility Information:
Facility Name
Woodland Research Northwest LLC - ERG - PPDS
City
Rogers
State/Province
Arkansas
ZIP/Postal Code
72758
Country
United States
Facility Name
Science 37, Inc
City
Los Angeles
State/Province
California
ZIP/Postal Code
90094
Country
United States
Facility Name
Allergy and Asthma Medical Group and Research Center - CRN - PPDS
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Invesclinic, LLC
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Advanced Pulmonary Research Institute
City
Loxahatchee Groves
State/Province
Florida
ZIP/Postal Code
33470
Country
United States
Facility Name
LCC Medical Research - Miami - BTC - PPDS
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Adult Medicine of Lake County
City
Mount Dora
State/Province
Florida
ZIP/Postal Code
32757
Country
United States
Facility Name
Providea Health Partners LLC
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
Facility Name
Clinical Research Institute, Inc - CRN - PPDS
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55402
Country
United States
Facility Name
Encompass Care
City
North Las Vegas
State/Province
Nevada
ZIP/Postal Code
89086
Country
United States
Facility Name
Riverside Medical Group - Circuit- PPDS
City
Secaucus
State/Province
New Jersey
ZIP/Postal Code
07094
Country
United States
Facility Name
NYC Health + Hospitals/Lincoln
City
Bronx
State/Province
New York
ZIP/Postal Code
10451
Country
United States
Facility Name
Elmhurst Hospital Center
City
Elmhurst
State/Province
New York
ZIP/Postal Code
11373
Country
United States
Facility Name
Harlem Hospital Center
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Premier Family Physicians - Austin - Hunt - PPDS
City
Austin
State/Province
Texas
ZIP/Postal Code
78735
Country
United States
Facility Name
Village Health Partners - Plano - Hunt - PPDS
City
Plano
State/Province
Texas
ZIP/Postal Code
75024
Country
United States
Facility Name
South Texas Allergy and Asthma Medical Professionals
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Boundary House Medical Centre
City
Sale
State/Province
Cheshire
ZIP/Postal Code
M33 2RH
Country
United Kingdom
Facility Name
St Mary's Hospital - PPDS
City
London
State/Province
City Of London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2Q
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
35244208
Citation
Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
Results Reference
derived

Learn more about this trial

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

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