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

Bill & Melinda Gates Medical Research Institute

Status and phase: Terminated; Phase 2

Conditions: COVID-19

Treatments: Drug: Placebo; Drug: Rivaroxaban

Study type: Interventional

Funder types: Other

Identifiers

NCT04504032

2020-005395-35 (EudraCT Number)

Gates MRI - COD-01-T01-01

Details and patient eligibility

About

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.

Enrollment: 497 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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497 participants in 2 patient groups, including a placebo group

Rivaroxaban

Experimental group

Treatment:

Drug: Rivaroxaban

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo