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 (PREVENT-HD)

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

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.

Study Overview

• Status: Terminated
• Conditions: Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Other: Standard of Care (SOC); Drug: Rivaroxaban; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1284
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • University of Arizona
  • California
    • Los Angeles, California, United States, 90027
      • Southern California Permanente Medical Group
    • Oakland, California, United States, 94612
      • Kaiser Permanente Northern California
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
    • Atlanta, Georgia, United States, 30310
      • Morehouse School Of Medicine
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore Universite Healthsystem
  • Maryland
    • Hagerstown, Maryland, United States, 21742
      • Meritus Center for Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10075
      • Lenox Hill Hospital -Northwell Health
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University Medical Center
  • Texas
    • Fort Worth, Texas, United States, 76107
      • Texas Health Physicians Group
  • Washington
    • Tacoma, Washington, United States, 98404
      • Franciscan Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Participants will receive rivaroxaban 10 milligram (mg) tablet orally once daily for 35 Days along with standard of care treatment (SOC).	Other: Standard of Care (SOC); SOC treatment will be determined by the investigator based on local practice and consists of supportive care.; Drug: Rivaroxaban; Participants will receive rivaroxaban 10 mg tablet orally once daily.; Other Names: JNJ-39039039; BAY 59-7939
Placebo Comparator: Placebo; Participants will receive matching placebo tablet orally once daily for 35 Days along with SOC.	Other: Standard of Care (SOC); SOC treatment will be determined by the investigator based on local practice and consists of supportive care.; Other: Placebo; Participants will receive matching placebo tablet orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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 May 8;147(25):1891-901. doi: 10.1161/CIRCULATIONAHA.123.063901. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: CR108849; 39039039DVT3004 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No