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COVID-19Phase 2NCT04504032

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

A Phase 2 study testing Rivaroxaban in people with COVID-19, run by Gates Medical Research Institute at 20 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19
What is being tested?
Rivaroxaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
497 participants
Where
20 sitesin 2 countries
Study dates
2 Sep 2020to 29 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
Show all 31Show fewer
  • 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

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

United States17 sites

  • Premier Family Physicians - Austin - Hunt - PPDS

    Austin, Texas, 78735

  • Elmhurst Hospital Center

    Elmhurst, New York, 11373

  • Providea Health Partners LLC

    Evergreen Park, Illinois, 60805

  • Invesclinic, LLC

    Fort Lauderdale, Florida, 33308

  • Science 37, Inc

    Los Angeles, California, 90094

  • Advanced Pulmonary Research Institute

    Loxahatchee Groves, Florida, 33470

  • LCC Medical Research - Miami - BTC - PPDS

    Miami, Florida, 33126

  • Clinical Research Institute, Inc - CRN - PPDS

    Minneapolis, Minnesota, 55402

  • Adult Medicine of Lake County

    Mt. Dora, Florida, 32757

  • Harlem Hospital Center

    New York, New York, 10037

  • Encompass Care

    North Las Vegas, Nevada, 89086

  • Village Health Partners - Plano - Hunt - PPDS

    Plano, Texas, 75024

  • Woodland Research Northwest LLC - ERG - PPDS

    Rogers, Arkansas, 72758

  • South Texas Allergy and Asthma Medical Professionals

    San Antonio, Texas, 78229

  • Allergy and Asthma Medical Group and Research Center - CRN - PPDS

    San Diego, California, 92123

  • Riverside Medical Group - Circuit- PPDS

    Secaucus, New Jersey, 07094

  • NYC Health + Hospitals/Lincoln

    The Bronx, New York, 10451

Other trials in United States

United Kingdom3 sites

  • St Mary's Hospital - PPDS

    London, City of London, W2 1NY

  • Royal Free Hospital

    London, NW3 2Q

  • Boundary House Medical Centre

    Sale, Cheshire, M33 2RH

Other trials in United Kingdom

About this study

Official title: A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19

The purpose of this study is to assess safety and clinical efficacy of rivaroxaban in people with mild Coronavirus Disease 2019 who are at increased risk of disease progression.

Conditions
COVID-19
Being tested
Rivaroxaban, Placebo
Keywords
Rivaroxaban, Xarelto, Coronavirus, COVID-19, Coronavirus disease 2019
Medical subject headings
COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RivaroxabanDrug

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

  • PlaceboDrug

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

Study groups in NCT04504032
Study groupRoleWhat they receive
RivaroxabanExperimentalNot described
Receives: Drug: Rivaroxaban
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to Day 35

  2. 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.

    Measured: Up to Day 35

  3. 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.

    Measured: Up to Day 35

  4. 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.

    Measured: Up to Day 28

Secondary outcomes (11)

  1. 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.

    Measured: Up to Day 28

  2. 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.

    Measured: Up to Day 28

  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

    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.

    Measured: Days 8, 14, and 21

  4. 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.

    Measured: Days 8, 14, 21, and 28

  5. 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.

    Measured: Days 8, 14, 21, and 28

  6. 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.

    Measured: Days 8, 14, 21, and 28

  7. 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.

    Measured: Days 8, 14, 21, and 28

  8. 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.

    Measured: Days 8, 14, 21, and 28

  9. 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.

    Measured: Up to Day 35

  10. 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.

    Measured: Days 8, 14, 21, and 28

  11. 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.

    Measured: Baseline; Days 8, 14, 21, and 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2020
  2. Study start2 Sep 2020
  3. Primary completion10 Mar 2021
  4. Study completion29 Mar 2021

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

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
497 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04504032
Sponsor's protocol ID
Gates MRI - COD-01-T01-01
Other IDs
2020-005395-35
Status last verified
Oct 2021
First submitted
5 Aug 2020
Last updated
22 Oct 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.

    PubMed 37591523

  • 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: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

    PubMed 35244208

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rivaroxaban in people with COVID-19, run by Gates Medical Research Institute at 20 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35 (time frame: Up to Day 35). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04504032, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2021.

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