A Trial to Evaluate Safety and Efficacy of Rivaroxaban (COVID-19)
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Rivaroxaban; Placebo
Intervention 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.
Intervention MeSH terms: Rivaroxaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 497.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rivaroxaban; Xarelto; Coronavirus; COVID-19; Coronavirus disease 2019

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.
    

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