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

Coronavirus Disease 2019 (COVID-19) Clinical Trial

— PREVENT-HD  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04508023
• Other study ID #: CR108849
• Secondary ID: 39039039DVT3004
• Status: Terminated
• Phase: Phase 3
• Start date: August 13, 2020
• Est. completion date: June 1, 2022

Study information

• Verified date: July 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1284
• Est. completion date: June 1, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Disease 2019 (COVID-19)
• Coronavirus Infections
• COVID-19

Intervention

Drug:
• Rivaroxaban
Participants will receive rivaroxaban 10 mg tablet orally once daily.

Other:
• Placebo
Participants will receive matching placebo tablet orally once daily.
• Standard of Care (SOC)
SOC treatment will be determined by the investigator based on local practice and consists of supportive care.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Henry Ford Hospital	Detroit	Michigan
United States	Northshore Universite Healthsystem	Evanston	Illinois
United States	Texas Health Physicians Group	Fort Worth	Texas
United States	Meritus Center for Clinical Research	Hagerstown	Maryland
United States	Southern California Permanente Medical Group	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Lenox Hill Hospital -Northwell Health	New York	New York
United States	Kaiser Permanente Northern California	Oakland	California
United States	Florida Hospital Orlando	Orlando	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Franciscan Research Center	Tacoma	Washington
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Random — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint	Number of participants with time to first occurrence of primary efficacy composite endpoint were reported. Time to first occurrence of primary efficacy composite endpoint is defined as time from randomization to first occurrence of any component of the primary endpoint. The components were: symptomatic venous thromboembolism (VTE), myocardial infarction (MI), ischemic stroke, acute limb ischemia, non-central nervous system (non-CNS) systemic embolization, all-cause hospitalization, and all-cause mortality.	Up to Day 35
Primary	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	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 ISTH criteria were reported. Fatal bleeding is defined as any bleeding event that leads to fatal outcome. Critical site bleeding defined as any bleeding event that occurred at critical site such as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal.	Up to Day 35
Secondary	Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes	Number of participants with time to the first occurrence of secondary efficacy outcomes which included thrombotic events (symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, non-CNS systemic embolization), emergency room (ER) visit, all-cause mortality, all-cause hospitalization, any thrombotic outcome and all-cause mortality, and any thrombotic outcome and all-cause hospitalization, were reported.	From Day 1 up to Day 35
Secondary	Number of Participants With Time to First Occurrence of Major Bleeding Based on a Modification of the ISTH Criteria	Number of participants with time to first occurrence of the major bleeding based on a modification of the ISTH criteria were reported. Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 grams per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.	Up to Day 35
Secondary	Number of Participants Who Were Hospitalized or Dead on Day 35	Number of participants who were hospitalized or dead on Day 35 were reported.	At Day 35 (+/- 6 days)