Back to resultsA 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)
Primary Purpose
Coronavirus Disease 2019 (COVID-19)
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rivaroxaban
Placebo
Standard of Care (SOC)
Sponsored by
About this trial
This is an interventional treatment trial for Coronavirus Disease 2019 (COVID-19)
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
Sites / Locations
- University of Arizona
- Southern California Permanente Medical Group
- Kaiser Permanente Northern California
- University of Colorado Denver
- Florida Hospital Orlando
- Emory University
- Morehouse School of Medicine
- Atlanta VA Medical Center
- Northshore Universite Healthsystem
- Meritus Center for Clinical Research
- Brigham & Women's Hospital
- Henry Ford Hospital
- Mayo Clinic
- Lenox Hill Hospital -Northwell Health
- Vanderbilt University Medical Center
- Texas Health Physicians Group
- Franciscan Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rivaroxaban
Placebo
Arm Description
Participants will receive rivaroxaban 10 milligram (mg) tablet orally once daily for 35 Days along with standard of care treatment (SOC).
Participants will receive matching placebo tablet orally once daily for 35 Days along with SOC.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Number of Participants Who Were Hospitalized or Dead on Day 35
Number of participants who were hospitalized or dead on Day 35 were reported.
Full Information
NCT ID
NCT04508023
First Posted
August 10, 2020
Last Updated
July 17, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT04508023
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated prematurely due to enrollment challenges.
Study Start Date
August 13, 2020 (Actual)
Primary Completion Date
June 1, 2022 (Actual)
Study Completion Date
June 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Disease 2019 (COVID-19)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1284 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rivaroxaban
Arm Type
Experimental
Arm Description
Participants will receive rivaroxaban 10 milligram (mg) tablet orally once daily for 35 Days along with standard of care treatment (SOC).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive matching placebo tablet orally once daily for 35 Days along with SOC.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
JNJ-39039039, BAY 59-7939
Intervention Description
Participants will receive rivaroxaban 10 mg tablet orally once daily.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching placebo tablet orally once daily.
Intervention Type
Other
Intervention Name(s)
Standard of Care (SOC)
Intervention Description
SOC treatment will be determined by the investigator based on local practice and consists of supportive care.
Primary Outcome Measure Information:
Title
Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint
Description
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.
Time Frame
Up to Day 35
Title
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
Description
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.
Time Frame
Up to Day 35
Secondary Outcome Measure Information:
Title
Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes
Description
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.
Time Frame
From Day 1 up to Day 35
Title
Number of Participants With Time to First Occurrence of Major Bleeding Based on a Modification of the ISTH Criteria
Description
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.
Time Frame
Up to Day 35
Title
Number of Participants Who Were Hospitalized or Dead on Day 35
Description
Number of participants who were hospitalized or dead on Day 35 were reported.
Time Frame
At Day 35 (+/- 6 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85721
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Kaiser Permanente Northern California
City
Oakland
State/Province
California
ZIP/Postal Code
94612
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Florida Hospital Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Morehouse School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30310
Country
United States
Facility Name
Atlanta VA Medical Center
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Northshore Universite Healthsystem
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Meritus Center for Clinical Research
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21742
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Lenox Hill Hospital -Northwell Health
City
New York
State/Province
New York
ZIP/Postal Code
10075
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37235
Country
United States
Facility Name
Texas Health Physicians Group
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76107
Country
United States
Facility Name
Franciscan Research Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98404
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Citations:
PubMed Identifier
37154020
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.
Results Reference
result
Learn more about this trial
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
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