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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prevention & Control	Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Aspirin; Drug: Aspirin placebo; Drug: Rivaroxaban placebo; Drug: Pantoprazole	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	27395 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	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).
Actual Study Start Date :	February 28, 2013
Actual Primary Completion Date :	July 21, 2017
Estimated Study Completion Date :	June 30, 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Rivaroxaban [2.5mg] + Aspirin; Rivaroxaban 2.5 mg twice daily and Aspirin 100 mg once daily. (Long-term open-label extension was added to make rivaroxaban 2.5 mg twice daily + aspirin 100 mg once daily available to COMPASS trial subjects until the rivaroxaban treatment is commercially available for this indication or for approximately 3 years from regulatory approval of the long term open label extension in a country, whichever comes first.)	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 2.5 mg twice daily, tablet; Drug: Aspirin; Aspirin 100 mg once daily, tablet; Drug: Pantoprazole; Subjects who are not on a proton pump inhibitor (PPI) will also be randomized to pantoprazole or pantoprazole placebo
Experimental: Rivaroxaban [5mg] + Placebo(1); Rivaroxaban 5 mg twice daily and Aspirin Placebo once daily	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban 5.0 mg twice daily, tablet; Drug: Aspirin placebo; Placebo(1), matching Aspirin tablets; Drug: Pantoprazole; Subjects who are not on a proton pump inhibitor (PPI) will also be randomized to pantoprazole or pantoprazole placebo
Active Comparator: Aspirin + Placebo(2); Rivaroxaban Placebo twice daily and Aspirin 100 mg once daily	Drug: Aspirin; Aspirin 100 mg once daily, tablet; Drug: Rivaroxaban placebo; Placebo(2), matching Rivaroxaban tablets; Drug: Pantoprazole; Subjects who are not on a proton pump inhibitor (PPI) will also be randomized to pantoprazole or pantoprazole placebo

Outcome Measures

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Primary Outcome Measures :

1. The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death [ Time Frame: 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. ]
   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.
2. The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria [ Time Frame: 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. ]

   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.

Secondary Outcome Measures :

1. The First Occurrence of Myocardial Infarction (MI), Ischemic Stroke, Acute Limb Ischemia (ALI), or Coronary Heart Disease (CHD) Death [ Time Frame: 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. ]
   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.
2. The First Occurrence of MI, Ischemic Stroke, ALI, or Cardiovascular (CV) Death [ Time Frame: 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. ]
   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.
3. All-cause Mortality [ Time Frame: 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. ]
   Count of participants and time from randomization to death by all cause were evaluated. Hazard ratios were calculated and reported as statistical analysis.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

-- Coronary or peripheral artery disease

Patients with coronary artery disease must also meet at least one of the following:

• 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:

• Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy or oral anticoagulant therapy
• 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

Contacts and Locations

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  Show 565 Study Locations

Sponsors and Collaborators

Bayer

Population Health Research Institute

Janssen Research & Development, LLC

Investigators

Study Director:	Bayer Study Director	Bayer

  Study Documents (Full-Text)

Documents provided by Bayer:

Study Protocol  [PDF] August 19, 2015

Statistical Analysis Plan  [PDF] March 31, 2017

More Information

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Additional Information:

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Publications of Results:

Anand SS, Caron F, Eikelboom JW, Bosch J, Dyal L, Aboyans V, Abola MT, Branch KRH, Keltai K, Bhatt DL, Verhamme P, Fox KAA, Cook-Bruns N, Lanius V, Connolly SJ, Yusuf S. Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial. J Am Coll Cardiol. 2018 May 22;71(20):2306-2315. doi: 10.1016/j.jacc.2018.03.008. Epub 2018 Mar 11.

Anand SS, Bosch J, Eikelboom JW, Connolly SJ, Diaz R, Widimsky P, Aboyans V, Alings M, Kakkar AK, Keltai K, Maggioni AP, Lewis BS, Störk S, Zhu J, Lopez-Jaramillo P, O'Donnell M, Commerford PJ, Vinereanu D, Pogosova N, Ryden L, Fox KAA, Bhatt DL, Misselwitz F, Varigos JD, Vanassche T, Avezum AA, Chen E, Branch K, Leong DP, Bangdiwala SI, Hart RG, Yusuf S; COMPASS Investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):219-229. doi: 10.1016/S0140-6736(17)32409-1. Epub 2017 Nov 10.

Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, Metsarinne K, O'Donnell M, Dans AL, Ha JW, Parkhomenko AN, Avezum AA, Lonn E, Lisheng L, Torp-Pedersen C, Widimsky P, Maggioni AP, Felix C, Keltai K, Hori M, Yusoff K, Guzik TJ, Bhatt DL, Branch KRH, Cook Bruns N, Berkowitz SD, Anand SS, Varigos JD, Fox KAA, Yusuf S; COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018 Jan 20;391(10117):205-218. doi: 10.1016/S0140-6736(17)32458-3. Epub 2017 Nov 10. Erratum in: Lancet. 2017 Dec 21;:.

Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Störk S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S; COMPASS Investigators. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017 Oct 5;377(14):1319-1330. doi: 10.1056/NEJMoa1709118. Epub 2017 Aug 27.

Responsible Party:	Bayer
ClinicalTrials.gov Identifier:	NCT01776424 History of Changes
Other Study ID Numbers:	15786; 2012-004180-43 ( EudraCT Number )
First Posted:	January 28, 2013
Results First Posted:	October 5, 2018
Last Update Posted:	December 10, 2018
Last Verified:	December 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Bayer:

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

Additional relevant MeSH terms:

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Aspirin; Rivaroxaban; Pantoprazole; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents	Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Anticoagulants