Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting

Study Overview
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Brief Summary
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Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting trial (TOP-CABG trial) is a multicenter, randomized, double-blind, non-inferiority, parallel controlled trial. The aim of TOP-CABG is to investigate whether de-escalated dual antiplatelet therapy (De-DAPT) is non-inferior to dual antiplatelet therapy (DAPT) in efficacy on inhibiting great saphenous vein (SVG) graft occlusion and is superior in reducing bleeding events in patients accepting coronary artery bypassing grafting.

Detailed Description
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After informed consent, at least 10 centers and 2,300 eligible admissions will be recruited. Eligible patients would be randomized (1:1) in double-blind manner (patients and treating physicians) to dual antiplatelet therapy (DAPT) group (ticagrelor 90mg bid and aspirin 100 mg qd for 12 month) and de-escalated DAPT (De-DAPT) group (90mg bid and aspirin 100 mg qd for first 3 months, and then aspirin 100 mg qd and placebo for 9 months).

Official Title
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Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting in Patients Without Acute Coronary Syndrome

Conditions
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Coronary Artery Disease, Coronary Artery Bypass Grafting, Dual Antiplatelet Therapy, Bleeding, Myocardial Infarction, Myocardial Ischemia, Angina Pectoris

Intervention / Treatment
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* Drug: De-escalated Dual Antiplatelet Therapy
* Drug: Dual Antiplatelet Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria 1. Patients 18-80 of age. 2. Patients undergo planned CABG for the first time with ≥1 SVGs 3. Patients with written informed consent. Exclusion criteria Concomitant valve (excluding aortic bioprosthesis), aorta, or rhythm surgery during the same session. Patients undergo emergency CABG. Patients with single coronary artery disease. Patients with cardiogenic shock and hemodynamic instability. Patients with sick sinus syndrome, 2nd or 3rd atrioventricular block. Patients with contraindications for coronary computed tomography angiography or coronary angiography (eg. contrast allergy). Use of other antiplatelet drugs than aspirin or ticagrelor (clopidogrel, prasugrel, etc) and unable to discontinue this medication after CABG, in the treating physician's or the investigator's opinion. Patients who take oral anticoagulants before CABG and have to use anticoagulants after surgery. Contraindication for the use of ticagrelor or aspirin (ie. history of bleeding diathesis within 3 months prior presentation, severe gastrointestinal bleeding within 1year prior presentation, peptic ulcer without gastrointestinal bleeding in past 3 years or history of intracranial hemorrhage, allergy, severe gastrointestinal reaction caused by aspirin). Placement of a drug-eluting stent in a coronary or cerebral artery within 6 months of CABG or placement of a bare-metal stent in a coronary or cerebral artery within 1 month of CABG Thrombocytopenia before CABG (< 100 x 109/L). patients with severe renal function impairment requiring dialysis or active liver disease, including patients with unexplained persistent elevated transaminase or any transaminase more than 3 times the normal limit. Use of strong inhibitors of CYP3A4 Patients who have to use methotrexate and ibuprofen. Patients with active malignant tumors with increase in bleeding risk in the investigator's opinion Pregnant patients, patients who have given birth within the past 90 days, or who are breastfeeding. Premenopausal women who do not take adequate contraception. Adequate contraception refers to the adoption of at least two reliable methods of contraception, one of which must be a barrier method of contraception. CABG volume of the surgeon less than 50.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dual Antiplatelet Therapy (DAPT)<br>DAPT with ticagrelor (90mg twice daily) + aspirin (100 mg once daily) for 1 year after CABG. | Drug: Dual Antiplatelet Therapy<br>* Ticagrelor (90mg twice daily) + aspirin (100 mg once daily) for 1 year post CABG.<br>|
| Experimental: De-escalated Dual Antiplatelet Therapy (De-DAPT)<br>De-DAPT referred to ticagrelor (90mg twice daily) + aspirin (100 mg once daily) during first 3 months post CABG, then switch to aspirin (100 mg once daily) + placebo (twice daily) for 9 months. | Drug: De-escalated Dual Antiplatelet Therapy<br>* ticagrelor (90mg twice daily) + aspirin (100 mg once daily) during first 3 months post CABG, then switching to aspirin (100 mg once daily) + placebo (twice daily) for 9 months.<br>* Other names: De-escalation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 100% great saphenous vein (SVG) grafts occlusions | 100% SVG During 0-day to 1-year after CABG (Fitz Gibbon grade O). SVG grafts were assessed by multislice computed tomographic angiography or coronary angiography and interpreted by an independent Image Data Review Centre blinded to treatment allocation | During 0-day to 1-year after CABG | 
| Bleeding events | Bleeding events as defined by the BARC classification ≥ 2 at 1 year after CABG. | During 0-day to 1-year after CABG | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVG Failure | a composite of SVG occlusion in any SVG as defined above, SVG revascularization, myocardial infarction in myocardial territory supplied by an SVG, or sudden death, as defined by the American College of Cardiology and American Heart Association and judged by an independent Clinical Endpoint Committee blinded to treatment allocation | During 0-day to 1-year after CABG | 
| Graft stenosis and occlusion | Significant (≥70%) venous or arterial graft stenosis and any (venous or arterial) graft occlusion | During 0-day to 1-year after CABG | 
| MACCE episodes | MACCE episodes within 1-year after CABG (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or revascularization), as defined by the American College of Cardiology and American Heart Association and judged by an independent Clinical Endpoint Committee blinded to treatment allocation | Within 1-year after CABG | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Bypass Grafting, Ticagrelor, Aspirin, Dual Antiplatelet Therapy, De-escalated Dual Antiplatelet Therapy, Great Saphenous Vein, Bleeding