Coronavirus Disease 2019 (COVID-19)
Conditions
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.
Interventions
DRUGRivaroxaban
Participants will receive rivaroxaban 10 mg tablet orally once daily.
OTHERPlacebo
Participants will receive matching placebo tablet orally once daily.
OTHERStandard of Care (SOC)
SOC treatment will be determined by the investigator based on local practice and consists of supportive care.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | From Day 1 up to Day 35 | 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 | Up to Day 35 | 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 | At Day 35 (+/- 6 days) | Number of participants who were hospitalized or dead on Day 35 were reported. |
Countries
United States
Participant flow
Pre-assignment details
Participants who were not treated with study drug were still followed-up as per the planned visits.
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban 10 Milligrams (mg) Eligible participants with symptomatic coronavirus disease 2019 (COVID-19) who were at risk of venous and arterial thrombotic complications, received rivaroxaban 10 mg, orally, once daily throughout the 35 days of double-blind treatment period along with ongoing standard of care medications for COVID-19 at the discretion of the treating physician. | 641 |
| Placebo Eligible participants with symptomatic COVID-19 who were at risk of venous and arterial thrombotic complications, received placebo matching to rivaroxaban, orally, once daily throughout the 35 days of double-blind treatment period along with ongoing standard of care medications for COVID-19 at the discretion of the treating physician. | 643 |
| Total | 1,284 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Rivaroxaban 10 Milligrams (mg) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 13.07 | 56 years STANDARD_DEVIATION 13.18 | 55.7 years STANDARD_DEVIATION 13.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 95 Participants | 192 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 520 Participants | 1028 Participants | 508 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants | 64 Participants | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 41 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 61 Participants | 126 Participants | 65 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 85 Participants | 175 Participants | 90 Participants |
| Race (NIH/OMB) White | 465 Participants | 929 Participants | 464 Participants |
| Region of Enrollment United States | 641 Participants | 1284 Participants | 643 Participants |
| Sex: Female, Male Female | 399 Participants | 783 Participants | 384 Participants |
| Sex: Female, Male Male | 242 Participants | 501 Participants | 259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 641 | 2 / 643 |
| other Total, other adverse events | 57 / 599 | 50 / 598 |
| serious Total, serious adverse events | 1 / 599 | 0 / 598 |
Outcome results
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.
Time frame: Up to Day 35
Population: Intent-To-Treat (ITT) analysis set included all randomized participants who provided informed consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint | 22 Participants |
| Placebo | Number of Participants With Time to First Occurrence of Primary Efficacy Composite Endpoint | 19 Participants |
p-value: 0.62695% CI: [0.63, 2.15]Log Rank
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.
Time frame: Up to Day 35
Population: The safety analysis set included participants in ITT who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rivaroxaban 10 Milligrams (mg) | 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 | Fatal Bleeding | 0 Participants |
| Rivaroxaban 10 Milligrams (mg) | 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 | Critical Site Bleeding | 0 Participants |
| Placebo | 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 | Fatal Bleeding | 0 Participants |
| Placebo | 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 | Critical Site Bleeding | 0 Participants |
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.
Time frame: At Day 35 (+/- 6 days)
Population: ITT analysis set included all randomized participants who provided informed consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rivaroxaban 10 Milligrams (mg) | Number of Participants Who Were Hospitalized or Dead on Day 35 | 5 Participants |
| Placebo | Number of Participants Who Were Hospitalized or Dead on Day 35 | 3 Participants |
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.
Time frame: Up to Day 35
Population: The safety analysis set included participants in ITT who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to First Occurrence of Major Bleeding Based on a Modification of the ISTH Criteria | 1 Participants |
| Placebo | Number of Participants With Time to First Occurrence of Major Bleeding Based on a Modification of the ISTH Criteria | 0 Participants |
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.
Time frame: From Day 1 up to Day 35
Population: ITT analysis set included all randomized participants who provided informed consent.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Ischemic stroke | 0 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Myocardial Infraction | 0 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | All-cause hospitalization | 21 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Acute limb ischemia | 0 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | All-cause Mortality | 2 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Symptomatic VTE | 0 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Any Thrombotic Outcome and All-cause Mortality | 2 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Non-CNS systemic embolization | 0 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Any Thrombotic Outcome and All-cause Hospitalization | 21 Participants |
| Rivaroxaban 10 Milligrams (mg) | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | ER Visit | 26 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Any Thrombotic Outcome and All-cause Hospitalization | 17 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Symptomatic VTE | 3 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Myocardial Infraction | 0 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Ischemic stroke | 2 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Acute limb ischemia | 0 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Non-CNS systemic embolization | 0 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | ER Visit | 34 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | All-cause hospitalization | 17 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | All-cause Mortality | 2 Participants |
| Placebo | Number of Participants With Time to the First Occurrence of Secondary Efficacy Outcomes | Any Thrombotic Outcome and All-cause Mortality | 7 Participants |