Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease

Study Overview
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Brief Summary
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The primary objectives of this study are: To determine whether rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg once daily (od) compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke, or cardiovascular death in subjects with coronary artery disease (CAD) or peripheral artery disease (PAD); To determine whether rivaroxaban 5 mg bid compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke or cardiovascular death in subjects with CAD or PAD.

Official Title
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A Randomized Controlled Trial of Rivaroxaban for the Prevention of Major Cardiovascular Events in Patients With Coronary or Peripheral Artery Disease (COMPASS - Cardiovascular OutcoMes for People Using Anticoagulation StrategieS).

Conditions
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Prevention & Control

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Aspirin
* Drug: Aspirin placebo
* Drug: Rivaroxaban placebo
* Drug: Pantoprazole
* Drug: Pantoprazole placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Meet criteria for CAD and/or PAD Subjects with CAD must also meet at least one of the following criteria: Age ≥65, or Age <65 and documented atherosclerosis or revascularization involving at least 2 vascular beds, or at least 2 additional risk factors Exclusion Criteria: Stroke within 1 month or any history of hemorrhagic or lacunar stroke Severe heart failure with known ejection fraction <30% or New York Heart Association (NYHA) class III or IV symptoms Estimated glomerular filtration rate (eGFR)<15 mL/min Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban 2.5mg + Aspirin 100mg<br>Participants received rivaroxaban 2.5 mg twice daily (bid) and aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were additionally randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. Participants who consented to LTOLE part received open label rivaroxaban 2.5 mg bid and aspirin 100 mg od in LTOLE part. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablet, 2.5 mg, twice daily, oral<br>Drug: Aspirin<br>* Tablet, 100 mg, once daily, oral<br>Drug: Pantoprazole<br>* Tablet, 40 mg, once daily, oral, for participants who were not on a PPI and who were randomized to pantoprazole<br>Drug: Pantoprazole placebo<br>* Pantoprazole matching placebo, once daily, oral, for participants who were not on a PPI and who were randomized to pantoprazole placebo<br>|
| Experimental: Rivaroxaban 5mg + Aspirin Placebo<br>Participants received rivaroxaban 5 mg bid and aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were additionally randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. Participants who consented to LTOLE part received open label rivaroxaban 2.5 mg bid and aspirin 100 mg od in LTOLE part. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablet, 5 mg, twice daily, oral<br>Drug: Aspirin placebo<br>* Aspirin matching placebo, once daily, oral<br>Drug: Pantoprazole<br>* Tablet, 40 mg, once daily, oral, for participants who were not on a PPI and who were randomized to pantoprazole<br>Drug: Pantoprazole placebo<br>* Pantoprazole matching placebo, once daily, oral, for participants who were not on a PPI and who were randomized to pantoprazole placebo<br>|
| Active Comparator: Rivaroxaban Placebo + Aspirin 100mg<br>Participants received rivaroxaban placebo bid and aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. Participants who consented to LTOLE part received open label rivaroxaban 2.5 mg bid and aspirin 100 mg od in LTOLE part. | Drug: Aspirin<br>* Tablet, 100 mg, once daily, oral<br>Drug: Rivaroxaban placebo<br>* Rivaroxaban matching placebo, twice daily, oral<br>Drug: Pantoprazole<br>* Tablet, 40 mg, once daily, oral, for participants who were not on a PPI and who were randomized to pantoprazole<br>Drug: Pantoprazole placebo<br>* Pantoprazole matching placebo, once daily, oral, for participants who were not on a PPI and who were randomized to pantoprazole placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death | Count of participants and time from randomization to the first occurrence of the composite primary efficacy outcome, MI, stroke, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis. | For each participant, the first occurrence of the composite primary efficacy outcome after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. | 
| The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria | Modified ISTH major bleeding is defined as: i) Fatal bleeding, or ii) Symptomatic bleeding in a critical area or organ, such as intraarticular, intracranial, intramuscular with compartment syndrome, intraocular, intraspinal, liver, pancreas, pericardial, respiratory, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation, or iii) Bleeding leading to hospitalization (major bleeding also includes presentation to an acute care facility with discharge on the same day). Count of participants and time from randomization to the first occurrence of the primary safety outcome major bleeding were evaluated. Hazard ratios were calculated and reported as statistical analysis. | For each participant, the first occurrence of modified ISTH major bleeding after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The First Occurrence of Myocardial Infarction (MI), Ischemic Stroke, Acute Limb Ischemia (ALI), or Coronary Heart Disease (CHD) Death | Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CHD death were evaluated. Hazard ratios were calculated and reported as statistical analysis. | For each participant, the first occurrence of MI, ALI, or CHD death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. | 
| The First Occurrence of MI, Ischemic Stroke, ALI, or Cardiovascular (CV) Death | Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis. | For each participant, the first occurrence of MI, ischemic stroke, ALI, or CV death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. | 
| All-cause Mortality | Count of participants and time from randomization to death by all cause were evaluated. Hazard ratios were calculated and reported as statistical analysis. | For each participants, death by any cause after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular events, Rivaroxaban, Xarelto, Anticoagulant, Blood thinner, Aspirin, ASA, Coronary artery disease, CAD, Peripheral artery disease, PAD, Artery disease, Coronary artery bypass graft, Stroke, Heart attack, Angina, Arterial vascular disease, Myocardial infarction, MI, Cardiovascular Death, CV Death, Heart disease