Ticagrelor and ASA vs. ASA Only After Isolated Coronary Artery Bypass Grafting in Patients With Acute Coronary Syndrome

Study Overview
=================
Brief Summary
-----------------
The study is a Randomised Registry-based Clinical Trial (RRCT) to assess whether dual antiplatelet therapy with ticagrelor and ASA compared to ASA alone improves outcome after isolated CABG in patients with acute coronary syndrome.

Detailed Description
-----------------
The trial is a 1:1 randomized, interventional, multi-national, multi-center, safety/efficacy, parallel assignment, open-label treatment study and will use the RRCT methodology. A RRCT study utilizes existing health care registry platforms to conduct a pragmatic prospective randomized trial. After the CABG, eligible patients that have consented to the study, will be randomized to either treatment arms. In the intervention arm, patients will be treated with ticagrelor 90 mg twice daily and ASA 75-100 mg daily for 12 months and patients in the control arm will get ASA only (75-160 mg daily according to local guidelines) during the same time period. The patients will be followed by telephone interviews at 30 days and 365 days after inclusion. After the treatment period patients will be followed during an observation period by collection of outcome data from registries or medical records, 24, 36, 60 and 120 months after inclusion of the patient. No other data but the registry data or data from medical records will be collected.

Official Title
-----------------
Dual Antiplatelet Therapy With Ticagrelor and Acetylsalicylic Acid (ASA) vs. ASA Only After Isolated Coronary Artery Bypass Grafting in Patient With Acute Coronary Syndrome

Conditions
-----------------
Acute Coronary Syndrome

Intervention / Treatment
-----------------
* Drug: Ticagrelor 90mg twice daily and ASA 75-100 mg daily
* Drug: ASA 75-160 mg daily


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Age ≥18 years Has undergone first time isolated CABG due to an episode of acute coronary syndrome (STEMI, NSTEMI, unstable angina) within 6 weeks before surgery Exclusion Criteria: Previously enrolled in this study (i.e. patient now at repeat encounter) Concomitant surgical procedure other than CABG Anticoagulant treatment after the operation (e.g. warfarin, direct thrombin inhibitors (dabigatran), FXa inhibitors (rivaroxaban, apixaban, heparin, low-molecular weight heparin, fondaparinux) Discharge from the operating hospital to an ICU at another hospital Pregnancy or lactation Known intolerance or contraindication to ticagrelor or ASA Any disorder that may interfere with drug absorption Any condition other than coronary artery disease with a life expectancy <12 months Known chronic liver disease, renal disease requiring dialysis or bleeding disorder Atrioventricular block II and III in patients without pacemaker Any other indication for dual antiplatelet therapy, i.e. recent stent implantation Debilitating stroke within 90 days before inclusion Previous intracranial bleeding Treatment with immunosuppressants (e.g. cyclosporine and tacrolimus) Treatment with strong CYP3A4-inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir or atazanavir) Any condition that in the opinion of the investigator may interfere with adherence to trial protocol Participation in any other clinical trial evaluating investigational products at the time for enrollment in this study

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Interventional Model Description: Parallel treatment arms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dual antiplatelet therapy<br>Ticagrelor 90 mg twice daily and ASA 75-100 mg daily for 12 months | Drug: Ticagrelor 90mg twice daily and ASA 75-100 mg daily<br>* Assess whether ticagrelor 90 mg twice daily and ASA 75-100 mg daily versus ASA 75-160 mg daily improves outcome after isolated coronary artery bypass grafting in patients with acute coronary syndrome<br>|
| Active Comparator: Acetylsalicylic acid<br>ASA 75-160 mg daily for 12 months | Drug: ASA 75-160 mg daily<br>* Assess whether ticagrelor 90 mg twice daily and ASA 75-100 mg daily versus ASA 75-160 mg daily improves outcome after isolated coronary artery bypass grafting in patients with acute coronary syndrome<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to major adverse cardiovascular events (MACE) | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone improves 12 months outcome defined as time to major adverse cardiovascular events (MACE) after isolated CABG in ACS patients. MACE includes all-cause mortality, myocardial infarction, stroke and new revascularization. | within12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to all cause death | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences all cause death within 12 months after randomization | within 12 months | 
| Time to all cause death, myocardial infarction or stroke | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone improves 12 months outcome defined as time to a composite endpoint of all cause death, myocardial infarction or stroke after isolated CABG in ACS patients. | within 12 months | 
| Time to cardiovascular death | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences cardiovascular death within 12 months after randomization | within 12 months | 
| Time to first myocardial infarction | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences myocardial infarction within 12 months after randomization | within 12 months | 
| Time to first stroke | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of stroke within 12 months after randomization | within 12 months | 
| Time to new revascularization | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of new revascularization within 12 months after randomization | within 12 months | 
| Time to coronary angiography | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of coronary angiography within 12 months after randomization | within 12 months | 
| Time to hospitalization for heart failure | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of heart failure within 12 months after randomization | within 12 months | 
| Time to cardiovascular hospitalization | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of cardiovascular hospitalization within 12 months after randomization | within 12 months | 
| Time to sudden death or aborted cardiac arrest | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of sudden death or aborted cardiac arrest within 12 months after randomization | within 12 months | 
| Time to new-onset atrial fibrillation | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of new-onset atrial fibrillation within 12 months after randomization | within 12 months | 
| Time to major bleeding defined as bleeding requiring hospitalization | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of major bleeding within 12 months after randomization | within 12 months | 
| Time to minor bleeding | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of minor bleeding within 12 months after randomization | within 12 months | 
| Time to any bleeding | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of any bleeding within 12 months after randomization | within 12 months | 
| Time to dyspnea | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of dyspnea within 12 months after randomization | within 12 months | 
| Time to dyspnea causing drug interruption | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of dyspnea causing drug interruption within 12 months after randomization | within 12 months | 
| Time to new onset renal failure | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone influences the incidence of new onset renal failure within 12 months after randomization | within 12 months | 
| Time to major adverse cardiovascular events (MACE) | To assess whether dual antiplatelet therapy (DAPT) with ticagrelor and ASA compared to single antiplatelet therapy with ASA alone improves long-term outcome defined as time to major adverse cardiovascular events (MACE) after isolated CABG in ACS patients. MACE includes all-cause mortality, myocardial infarction, stroke and new revascularization. | 2, 3, 5 and 10 years after the patient has been included in the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronary Bypass Grafting, Antiplatelet treatment