A Study Exploring Two Strategies of Rivaroxaban (JNJ39039039; BAY-59-7939) and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety for 2 different rivaroxaban treatment strategies and one Vitamin K Antagonist (VKA) treatment strategy utilizing various combinations of dual antiplatelet therapy (DAPT) or low-dose aspirin (ASA) or clopidogrel (or prasugrel or ticagrelor).

Detailed Description
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This is an open-label (both physician and participant know the treatment that the participant receives), randomized (study medication is assigned by chance), multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and one vitamin K antagonist (VKA) treatment strategy in participants, who have paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) and have had a percutaneous coronary intervention (PCI) with stent placement. A target of 2,100 participants will be randomized into the study, with approximately 700 participants in each treatment strategy group. The randomization will be stratified by the intended duration of DAPT (1, 6, or 12 months). The study consists of a screening phase, a 12-month open-label treatment phase, and an end-of-treatment/early withdrawal visit. The total duration of participation in the study for each participant is approximately 12 months.

Official Title
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An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention

Conditions
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Atrial Fibrillation, Percutaneous Coronary Intervention

Intervention / Treatment
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* Drug: rivaroxaban 2.5 mg
* Drug: rivaroxaban 15 mg
* Drug: rivaroxaban 10 mg
* Drug: aspirin (ASA)
* Drug: vitamin K antagonist (VKA)
* Drug: clopidogrel
* Drug: prasugrel
* Drug: ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a documented medical history of paroxysmal, persistent, or permanent non-valvular atrial fibrillation (AF) Have undergone percutaneous coronary intervention (PCI) procedure (with stent placement) for primary atherosclerotic disease Must have an international normalized ratio (INR) of 2.5 or below to be randomized Women must be postmenopausal before entry or practicing a highly effective method of birth control when heterosexually active Be willing and able to adhere to the prohibitions and restrictions specified in the study protocol Exclusion Criteria: Have any condition that contraindicates anticoagulant or antiplatelet therapy or would have an unacceptable risk of bleeding, such as, but not limited to: platelet count <90,000/microliter at screening, history of intracranial hemorrhage, 12 month history of clinically significant gastrointestinal bleeding, non-VKA induced elevated prothrombin time (PT) at screening Have anemia of unknown cause with a hemoglobin level <10 g/dL (<6.21 mmol/L) Have a history of stroke or Transient Ischemic Attack (TIA) Have a calculated Creatinine Clearance (CrCl) <30 mL/min at screening Have known significant liver disease or liver function test (LFT) abnormalities Have any severe condition that would limit life expectancy to less than 12 months

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rivaroxaban 2.5 mg twice daily<br>rivaroxaban 2.5 mg tablet twice daily plus low-dose aspirin (ASA) 75 to 100 mg once daily and clopidogrel 75 mg tablet once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) followed by rivaroxaban 15 mg tablet (or 10 mg for subjects with moderate renal impairment) once daily plus low-dose ASA for 12 months | Drug: rivaroxaban 2.5 mg<br>* One 2.5 mg tablet twice daily for up to twelve months<br>Drug: rivaroxaban 15 mg<br>* One 15 mg tablet once daily for up to twelve months<br>Drug: rivaroxaban 10 mg<br>* One 10 mg tablet once daily for up to twelve months<br>Drug: aspirin (ASA)<br>* Low-dose aspirin tablet once daily for twelve months<br>Drug: clopidogrel<br>* One 75 mg tablet once daily for up to twelve months<br>Drug: prasugrel<br>* One 10 mg tablet once daily for up to twelve months<br>Drug: ticagrelor<br>* One 90 mg tablet twice daily for up to twelve months<br>|
| Experimental: vitamin K antagonist (VKA)<br>dose-adjusted vitamin K antagonist (VKA) once daily (target International Normalized Ratio (INR) 2.0 to 3.0) plus low-dose ASA, 75 to 100 mg per day, and clopidogrel 75 mg once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) followed by dose-adjusted VKA once daily (target INR 2.0 to 3.0 or 2.0 to 2.5 at the investigator discretion) plus low-dose ASA for 12 months | Drug: aspirin (ASA)<br>* Low-dose aspirin tablet once daily for twelve months<br>Drug: vitamin K antagonist (VKA)<br>* Dose-adjusted VKA tablet (target International Normalized Ratio (INR) 2.0 to 3.0) once daily for twelve months<br>Drug: clopidogrel<br>* One 75 mg tablet once daily for up to twelve months<br>Drug: prasugrel<br>* One 10 mg tablet once daily for up to twelve months<br>Drug: ticagrelor<br>* One 90 mg tablet twice daily for up to twelve months<br>|
| Experimental: rivaroxaban 15 mg once daily<br>rivaroxaban 15 mg (or 10 mg for subjects with moderate renal impairment) once daily plus clopidogrel 75 mg tablet once daily (or prasugrel 10 mg tablet once daily or ticagrelor 90 mg tablet twice daily) for 12 months | Drug: rivaroxaban 15 mg<br>* One 15 mg tablet once daily for up to twelve months<br>Drug: rivaroxaban 10 mg<br>* One 10 mg tablet once daily for up to twelve months<br>Drug: clopidogrel<br>* One 75 mg tablet once daily for up to twelve months<br>Drug: prasugrel<br>* One 10 mg tablet once daily for up to twelve months<br>Drug: ticagrelor<br>* One 90 mg tablet twice daily for up to twelve months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinically Significant Bleeding | Clinically significant bleeding is a composite of Thrombolysis in Myocardial Infarction (TIMI) major bleeding, minor bleeding, and bleeding requiring medical attention (BRMA). TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of greater than or equal to (>=) 5 grams per deciliter (g/dL) (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of >=15 percent (%)). TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to less than (<) 5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to <15 percent). A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event. | Up to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | TIMI major bleeding is defined as any symptomatic intracranial hemorrhage, Clinically overt signs of hemorrhage (including imaging) associated with a drop in hemoglobin of >= 5 g/dL (or when the hemoglobin concentration is not available, an absolute drop in hematocrit of >=15 percent). | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Minor Bleeding | TIMI minor bleeding event is defined as any clinically overt sign of hemorrhage (including imaging) that is associated with a fall in hemoglobin concentration of 3 to <5 g/dL (or, when hemoglobin concentration is not available, a fall in hematocrit of 9 percent to <15 percent). | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Bleeding Requiring Medical Attention (BRMA) | A BRMA event is defined as any bleeding event that requires medical treatment, surgical treatment, or laboratory evaluation, and does not meet criteria for a major or minor bleeding event. | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Composite of Adverse Cardiovascular Events (Cardiovascular Death, Myocardial Infarction (MI) and Stroke) | Percentage of participants who experienced adverse cardiovascular events (cardiovascular death, myocardial Infarction (MI) and stroke) collectively, were assessed. | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Cardiovascular Death | The percentage of participants with the first occurrence of cardiovascular death were evaluated. | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Myocardial Infarction | The percentage of participants with the first occurrence of Myocardial Infarction were evaluated. | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Stroke | The percentage of participants with the first occurrence of Stroke were evaluated. | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 
| Percentage of Participants With Stent Thrombosis | The percentage of participants with the first occurrence of stent thrombosis were evaluated. | Up to Month 12 and end of DAPT-Month 1, 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Irregular heart beat, rivaroxaban, aspirin, clopidogrel, prasugrel, ticagrelor, vitamin K antagonist