Coronavirus Disease 2019 (COVID-19)Phase 3PREVENT-HDNCT04508023
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
A Phase 3 study testing Rivaroxaban in people with Coronavirus Disease 2019 (COVID-19), run by Janssen Research & Development, LLC at 17 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronavirus Disease 2019 (COVID-19)
- What is being tested?
- Rivaroxaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,284 participants
- Where
- 17 sitesUnited States
- Study dates
- 13 Aug 2020to 1 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Emory University
Atlanta, Georgia, 30308
Morehouse School of Medicine
Atlanta, Georgia, 30310
University of Colorado Denver
Aurora, Colorado, 80045
Brigham & Women's Hospital
Boston, Massachusetts, 02115
Atlanta VA Medical Center
Decatur, Georgia, 30033
Henry Ford Hospital
Detroit, Michigan, 48202
Northshore Universite Healthsystem
Evanston, Illinois, 60201
Texas Health Physicians Group
Fort Worth, Texas, 76107
Meritus Center for Clinical Research
Hagerstown, Maryland, 21742
Southern California Permanente Medical Group
Los Angeles, California, 90027
Vanderbilt University Medical Center
Nashville, Tennessee, 37235
Lenox Hill Hospital -Northwell Health
New York, New York, 10075
Kaiser Permanente Northern California
Oakland, California, 94612
Florida Hospital Orlando
Orlando, Florida, 32803
Mayo Clinic
Rochester, Minnesota, 55905
Franciscan Research Center
Tacoma, Washington, 98404
University of Arizona
Tucson, Arizona, 85721
About this study
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
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.
- Conditions
- Coronavirus Disease 2019 (COVID-19)
- Being tested
- Rivaroxaban, Placebo, Standard of Care (SOC)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
Also called JNJ-39039039, BAY 59-7939
Participants will receive rivaroxaban 10 mg tablet orally once daily.
PlaceboOther
Participants will receive matching placebo tablet orally once daily.
Standard of Care (SOC)Other
SOC treatment will be determined by the investigator based on local practice and consists of supportive care.
| Study group | Role | What they receive |
|---|---|---|
| Rivaroxaban | Experimental | Participants will receive rivaroxaban 10 milligram (mg) tablet orally once daily for 35 Days along with standard of care treatment (SOC). Receives: Drug: Rivaroxaban; Other: Standard of Care (SOC) |
| Placebo | Placebo comparator | Participants will receive matching placebo tablet orally once daily for 35 Days along with SOC. Receives: Other: Placebo; Other: Standard of Care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to Day 35
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: At Day 35 (+/- 6 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2020
- Study start13 Aug 2020
- Primary completion1 Jun 2022
- Study completion1 Jun 2022
Why it stopped: The study was terminated prematurely due to enrollment challenges.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronavirus Disease 2019 (COVID-19)Studies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,284 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04508023
- Sponsor's protocol ID
- CR108849
- Other IDs
- 39039039DVT3004
- Acronym
- PREVENT-HD
- Status last verified
- Jul 2023
- First submitted
- 10 Aug 2020
- Last updated
- 18 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
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 Jun 20;147(25):1891-1901. doi: 10.1161/CIRCULATIONAHA.123.063901. Epub 2023 May 8.
PubMed 37154020Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.
PubMed 37591523
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04508023
- Acronym / sponsor ID
- PREVENT-HD / CR108849
- Conditions
- Coronavirus Disease 2019 (COVID-19)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated prematurely due to enrollment challenges.
- Enrolment
- 1,284 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 13 Aug 2020 (actual)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 11 Aug 2020 (actual)
- Results
- Posted 18 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban | Experimental | Drug: Rivaroxaban, Other: Standard of Care (SOC)Participants will receive rivaroxaban 10 milligram (mg) tablet orally once daily for 35 Days along with standard of care treatment (SOC). |
| Placebo | Placebo comparator | Other: Placebo, Other: Standard of Care (SOC)Participants will receive matching placebo tablet orally once daily for 35 Days along with SOC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivaroxabanAlso: JNJ-39039039, BAY 59-7939Participants will receive rivaroxaban 10 mg tablet orally once daily. | Drug | Rivaroxaban |
| PlaceboParticipants will receive matching placebo tablet orally once daily. | Other | Placebo |
| Standard of Care (SOC)SOC treatment will be determined by the investigator based on local practice and consists of supportive care. | Other | Placebo, Rivaroxaban |
Primary outcome
Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint
Time frame: Up to Day 35
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
Time frame: 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 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.
3 secondary outcomes
Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes
Time frame: 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
Time frame: Up to Day 35
Number of Participants Who Were Hospitalized or Dead on Day 35
Time frame: At Day 35 (+/- 6 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37154020Piazza 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.
- Derived from this study: PubMed 37591523Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rivaroxaban in people with Coronavirus Disease 2019 (COVID-19), run by Janssen Research & Development, LLC at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint (time frame: Up to Day 35). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04508023, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2023.