DUAL Antithrombotic Therapy in Patients With AF and ACS

Study Overview
=================
Brief Summary
-----------------
The study aims to show inferiority of rivaroxaban plus ticagrelor when compared to rivaroxaban plus clopidogrel in terms of safety. Safety will be determined by comparing the rates of death or ischemic event-including myocardial infarction, definite or probable stent thrombosis, stroke, or urgent revascularization.

Detailed Description
-----------------
The main objective of this study is to compare a Dual Antithrombotic Therapy (DAT) regimen of rivaroxaban plus ticagrelor with rivaroxaban plus clopidogrel in Patients With Non Valvular Atrial Fibrillation (NVAF) and Acute Coronary Syndrome. The study aims to show inferiority of rivaroxaban plus ticagrelor when compared to rivaroxaban plus clopidogrel in terms of safety. Safety will be determined by comparing the rates of death or ischemic event-including myocardial infarction, definite or probable stent thrombosis, stroke, or urgent revascularization.

Official Title
-----------------
An Open-label, Randomized, Controlled, Multicenter Study to Evaluate DUAL Antithrombotic Therapy With Rivaroxaban Plus Ticagrelor vs. Rivaroxaban Plus Clopidogrel in Patients With Atrial Fibrillation and Acute Coronary Syndrome

Conditions
-----------------
Atrial Fibrillation, Acute Coronary Syndromes

Intervention / Treatment
-----------------
* Drug: Rivaroxaban 15 MG Oral Tablet
* Drug: Clopidogrel 75 Mg Oral Tablet
* Drug: Ticagrelor 90 MG Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults with either active or a history of non-valvular atrial fibrillation or flutter with the planned or existing use of an oral anticoagulant for prophylaxis of thromboembolism. In addition, subjects must have had an acute coronary syndrome Planned use of antiplatelet agents for at least 12 months Males and Females ≥ 18 years of age Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug Exclusion Criteria: Conditions other than atrial fibrillation that require chronic anticoagulation. (e.g. prosthetic mechanical heart valve) Severe renal insufficiency (serum creatinine > 2.5 mg/dL or a calculated creatinine clearance < 30 mL/min Patients with a history of intracranial hemorrhage Patients have had or will undergo Coronary arterial bypass graft (CABG) for their index acute coronary syndrome (ACS) event Patients with known ongoing bleeding and patients with known coagulopathies Any contraindications or allergies to rivaroxaban, or to intended P2Y12 antagonists Have a history of stroke or Transient Ischemic Attack (TIA) 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
-----------------
Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 plus ticagrelor<br>rivaroxaban 15 mg (or 10 mg for subjects with moderate renal impairment) once daily plus ticagrelor 90 mg tablet twice daily for 12 months | Drug: Rivaroxaban 15 MG Oral Tablet<br>* One 15 mg tablet once daily for up to twelve months<br>* Other names: Xarelto;Drug: Ticagrelor 90 MG Oral Tablet<br>* One 90 mg tablet twice daily for up to twelve months<br>* Other names: P2Y12 antagonists;|
| Active Comparator: rivaroxaban plus clopidogrel<br>rivaroxaban 15 mg (or 10 mg for subjects with moderate renal impairment) once daily plus clopidogrel 75 mg tablet once daily for 12 months | Drug: Rivaroxaban 15 MG Oral Tablet<br>* One 15 mg tablet once daily for up to twelve months<br>* Other names: Xarelto;Drug: Clopidogrel 75 Mg Oral Tablet<br>* One 75 mg tablet once daily for up to twelve months<br>* Other names: P2Y12 antagonists;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The composite endpoints of death and ischemic events | The composite endpoints of death and ischemic events (stroke, myocardial infarction, stent thrombosis, urgent revascularization ) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | one year |