A Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to estimate the risk of bleeding with rivaroxaban, compared with acetylsalicylic acid (ASA), in addition to a single antiplatelet/ platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor agent: clopidogrel or ticagrelor), in participants with a recent acute coronary syndrome (ACS: including ST segment elevation myocardial infarction [STEMI] and non-ST-segment elevation acute coronary syndrome [NSTE-ACS]).

Detailed Description
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This is a prospective, randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel group (each group of participants will be treated at the same time), multicenter (when more than one hospital or medical school team work on a medical research study) study in participants with a recent ACS (STEMI or NSTE-ACS). All the eligible participants receiving background treatment of ASA plus clopidogrel (Stratum 1) or ASA plus ticagrelor (Stratum 2) will be randomly assigned to either receive ASA or rivaroxaban on background of P2Y12 receptor antagonists treatment. This study will include 3 phases: Screening Phase (up to 10 days, before study start on Day 1), Double-blind Treatment Phase (up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier), and Follow-up Phase (up to 30 days). Participants' safety will be monitored throughout the study.

Official Title
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A Randomized, Double-Blind, Double-Dummy, Active-controlled, Parallel-group, Multicenter Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Subjects With Acute Coronary Syndrome

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Acetylsalicylic acid
* Drug: Rivaroxaban
* Drug: Clopidogrel
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants, 18 years or older, must have symptoms suggestive of acute coronary syndrome (ACS) (angina, or symptoms thought to be equivalent) within 48 hours of hospital presentation, or developed ACS while being hospitalized, and has a diagnosis of: a) ST segment elevation myocardial infarction (STEMI); b) non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, participant who is 54 years of age or younger must also have either diabetes mellitus or a history of a prior myocardial infarction (MI), in addition to the presenting ACS event Participant must be randomized within the screening window of 10 days after hospital admission for the index ACS event. Participant should have received acute phase treatment for the index ACS, such as intravenous anticoagulant or antiplatelet, and are receiving maintenance dual antiplatelet therapy (DAPT) with either clopidogrel plus acetyl salicylic acid (ASA), or ticagrelor plus ASA, with the intent to continue the treatment with a platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor) after randomization Participants must agree to provide a pharmacogenomics deoxyribonucleic acid (DNA) sample Exclusion Criteria: Participant has any conditions that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk Participant with a prior stroke of any etiology or transient ischemic attack (TIA) Participant who received thrombolytic therapy as treatment for the index ACS event cannot be enrolled in the ticagrelor stratum Participant has anticipated need for chronic administration of omeprazole or esomeprazole concomitantly with clopidogrel Participant has known allergy or intolerance to ASA or rivaroxaban

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stratum 1/ASA<br>Acetylsalicylic acid (ASA) 100 milligram (mg) enteric-coated tablet once daily orally along with clopidogrel 75 mg once daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. | Drug: Acetylsalicylic acid<br>* ASA 100 mg enteric-coated tablet once daily orally.<br>* Other names: Aspirin;Drug: Clopidogrel<br>* Clopidogrel 75 mg once daily orally.<br>* Other names: Plavix;|
| Experimental: Stratum 1/Rivaroxaban<br>Rivaroxaban 2.5 mg tablet twice daily orally along with clopidogrel 75 mg once daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. | Drug: Rivaroxaban<br>* Rivaroxaban 2.5 mg tablet twice daily orally.<br>* Other names: Xarelto;Drug: Clopidogrel<br>* Clopidogrel 75 mg once daily orally.<br>* Other names: Plavix;|
| Active Comparator: Stratum 2/ASA<br>ASA 100 mg enteric-coated tablet once daily orally along with ticagrelor 90 mg twice daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. | Drug: Acetylsalicylic acid<br>* ASA 100 mg enteric-coated tablet once daily orally.<br>* Other names: Aspirin;Drug: Ticagrelor<br>* Ticagrelor 90 mg twice daily orally.<br>* Other names: Brilinta;|
| Experimental: Stratum 2/Rivaroxaban<br>Rivaroxaban 2.5 mg tablet twice daily orally along with ticagrelor 90 mg twice daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier. | Drug: Rivaroxaban<br>* Rivaroxaban 2.5 mg tablet twice daily orally.<br>* Other names: Xarelto;Drug: Ticagrelor<br>* Ticagrelor 90 mg twice daily orally.<br>* Other names: Brilinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Non Coronary Artery Bypass Graft-Related (Non CABG-related) Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events | Non CABG-related TIMI clinically significant bleeding events are sum of non CABG-related TIMI major bleeding events, TIMI minor bleeding events and TIMI bleeding events requiring medical attention. Major: any symptomatic intracranial bleeding: clinically overt signs of hemorrhage with hemoglobin (Hb) drop of greater than or equal to (>=)5 gram per deciliter (g/dl) (or absolute drop in hematocrit of >=15%) and fatal bleeding (results in death within 7 days); Minor: clinically overt sign of hemorrhage with Hb drop of 3 - <5 g/dl (or drop in hematocrit of 9 - <15%); requiring medical attention: bleeding event that required medical, surgical treatment/laboratory evaluation and did not meet criteria for major/minor bleeding event. | From start of study treatment until follow-up (up to 390 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndrome, Myocardial infarction, Unstable angina, Acetylsalicylic acid, Rivaroxaban, JNJ-39039039, Bay 59-7939, Xarelto, Clopidogrel, Ticagrelor, Plavix, Brilinta, Effient