Intervention: Rivaroxaban
Trial phase: Phase 2
ATC code: B01AF01
SMILES: O=C(NC[C@H]1CN(c2ccc(N3CCOCC3=O)cc2)C(=O)O1)c1ccc(Cl)s1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 219
Group description: Participants self-administered rivaroxaban 10 milligrams (mg) (1 tablet) orally once daily for 21 days.
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