Clinical trial NCT04508023: A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic Coronavirus Disease 2019 (COVID-19) Infection
Official title: A Multicenter, Randomized, Placebo-Controlled, Pragmatic Phase 3 Study Investigating the Efficacy and Safety of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19 Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronavirus Disease 2019 (COVID-19)
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-08-11
Enrollment: 1284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether rivaroxaban reduces the risk of a composite endpoint of major venous and arterial thrombotic events, all-cause hospitalization, and all-cause mortality compared with placebo in outpatients with acute, symptomatic Coronavirus Disease 2019 (COVID-19) Infection.


Eligibility criteria: Inclusion Criteria:

* Coronavirus Disease 2019 (COVID-19) positive diagnosis by locally obtained viral diagnostic test (example, polymerase chain reaction \[PCR\]). This may be nasal swab or saliva test or other available technology to demonstrate current infection
* Confirm that participant is known to health system, with at least 1 contact in electronic medical records (EMR) prior to screening
* Symptoms attributable to COVID-19 (example, fever, cough, loss of taste or smell, muscle aches, shortness of breath, fatigue)
* Initial treatment plan does not include hospitalization
* Presence of at least 1 additional risk factor: a) age more than or equal to (\>=) 60 years; b) prior history of VTE; c) history of thrombophilia; d) history of coronary artery disease (CAD); e) history of peripheral artery disease (PAD); f) history of cerebrovascular disease or ischemic stroke; g) history of cancer (other than basal cell carcinoma) h) history of diabetes requiring medication; i) history of heart failure; j) body mass index (BMI) greater than or equal to (\>=) 35 kilogram per meter square (kg/m\^2); k) D-dimer greater than (\>) upper limit of normal for local laboratory (within 2 weeks of the date of the COVID-19 test and prior to randomization)

Exclusion Criteria:

* Increased risk of bleeding such as a) significant bleeding in the last 3 months; b) active gastroduodenal ulcer in the last 3 months; c) history of bronchiectasis or pulmonary cavitation; d) need for dual antiplatelet therapy or anticoagulation; e) prior intracranial hemorrhage, f) known severe thrombocytopenia g) active cancer and undergoing treatment
* Any illness or condition that in the opinion of the investigator would significantly increase the risk of bleeding (example recent trauma, recent surgery, severe uncontrolled hypertension, gastrointestinal cancer, renal failure requiring dialysis, severe liver disease, known bleeding diathesis)
* Known allergies, hypersensitivity, or intolerance to rivaroxaban or its excipients
* Positive COVID-19 antibody or serology test after 2-week period of acute, symptomatic COVID-19 infection
* Known diagnosis of triple positive (positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies) antiphospholipid syndrome

Primary outcomes:
measure: Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint
timeFrame: Up to Day 35
measure: Number of Participants With Time to First Occurrence of The Principle Safety Outcome (Fatal Bleeding and Critical Site Bleeding) Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria
timeFrame: Up to Day 35
Secondary outcomes:
measure: Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes
timeFrame: From Day 1 up to Day 35
measure: Number of Participants With Time to First Occurrence of Major Bleeding Based on a Modification of the ISTH Criteria
timeFrame: Up to Day 35
measure: Number of Participants Who Were Hospitalized or Dead on Day 35
timeFrame: At Day 35 (+/- 6 days)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Northern California
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Evanston
country: United States
facility: Northshore Universite Healthsystem
state: Illinois
city: Hagerstown
country: United States
facility: Meritus Center for Clinical Research
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Lenox Hill Hospital -Northwell Health
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Texas Health Physicians Group
state: Texas
city: Tacoma
country: United States
facility: Franciscan Research Center
state: Washington
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Piazza G, Spyropoulos AC, Hsia J, Goldin M, Towner WJ, Go AS, Bull TM, Weng S, Lipardi C, Barnathan ES, Bonaca MP; PREVENT-HD Investigators. Rivaroxaban for Prevention of Thrombotic Events, Hospitalization, and Death in Outpatients With COVID-19: A Randomized Clinical Trial. Circulation. 2023 Jun 20;147(25):1891-1901. doi: 10.1161/CIRCULATIONAHA.123.063901. Epub 2023 May 8.