A Single-center, Prospective,Randomized Study of Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Dual Anti-platelet Therapy After Coronary Artery Bypass Grafting

Study Overview
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Brief Summary
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This study is designed to demonstrate that the onset of the antiplatelet effect of 90mg bid dose ticagrelor is more rapid and greater than 75 mg qd dose clopidogrel in patients undergoing CABG surgery.

Detailed Description
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Patients undergoing coronary artery surgery routinely receive aspirin therapy, as a standard treatment for preserving bypass graft patency. Although the dual antiplatelet therapy post CABG has not been recommended by guideline, present studies indicated the patients could benefit from the dual anti-platelet therapy. Using clopidogrel+aspirin could significantly reduce the early saphenous vein graft occlusion. . Many surgeons empirically prescribe dual anti-platelet therapy in spite of the indeterminacy of the clinical effects. ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y12-receptor antagonist. The ONSET/OFFSET Study also shows that ticagrelor achieved much rapid and greater platelet inhibition than high-loading-dose clopidogrel in patients with stable CAD. ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y12-receptor antagonist. The ONSET/OFFSET Study also shows that ticagrelor achieved much rapid and greater platelet inhibition than high-loading-dose clopidogrel in patients with stable CAD.

Official Title
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A Single-center, Prospective,Randomized Study of Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Dual Anti-platelet Therapy After Coronary Artery Bypass Grafting

Conditions
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Antiplatelet Therapy of Coronary Artery Bypass

Intervention / Treatment
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* Drug: ticagrelor
* Drug: clopidogrel
* Drug: asprin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and/or male and ≥ 18 and <80 years of age Isolated CABG for the first time either on- or off- pump Exclusion Criteria: Combined valvular surgery. A second surgery. Emergency surgery (a selective operation which change to emergency surgery in some special medical condition). Serum creatinine>130μmol/L. Oral clopidogrel therapy stops less than 5 days before the surgery. Oral anti-coagulation therapy (warfarin) that cannot be withheld. History of gastrointestinal or vaginal bleeding, Active pathological bleeding (e.g. active gastroduodenal ulcer or cerebral haemorrhage), history of postoperative gastrointestinal bleeding. Uric acid nephropathy, history of postoperative gastrointestinal bleeding. History of cerebral haemorrhage. Any other condition that may influence platelet count and function. Postoperative chest drainage > 200 ml/hr for two hours and more, re-operation for bleeding with persistent cardiac tamponade. Treated with IABP or ECMO after operation. Any other condition that may put the patient at risk (e.g., recurrent ventricular arrhythmias, peri-operative myocardial infarction, cancer). Contraindication to aspirin, clopidogrel and ticagrelor or other reason that study drug should not be administered (e.g., hypersensitivity, moderate or severe liver disease). Previous enrollment in other investigational drug or device study within 30 days. Being or planning to pregnant.

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
Interventional Model Description: Single center prospective randomized controlled study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ticagrelor<br>90mg Bid for 30days after first dose | Drug: ticagrelor<br>* After the operation, the subjects will be randomized into two groups according to the proportion of 1:1; and receive the treatment of aspirin 100mg qd+ticagrelor 90mg bid or the treatment of aspirin 100mg qd+ clopidogrel 75mg qd. The study will plan to enroll 140 subjects in 12 months and the treatment will last for 30 days.<br>|
| Active Comparator: clopidogrel<br>75mg Qd for 30days first dose | Drug: clopidogrel<br>* After the operation, the subjects will be randomized into two groups according to the proportion of 1:1; and receive the treatment of aspirin 100mg qd+ticagrelor 90mg bid or the treatment of aspirin 100mg qd+ clopidogrel 75mg qd. The study will plan to enroll 140 subjects in 12 months and the treatment will last for 30 days.<br>|
| Other: asprin<br>100mg Qd all patients will be given asprin 100mg Qd within 24hours after CABG | Drug: asprin<br>* All patients will be given asprin 100mg Qd within 24hours after operation,and will continue taking aspirin at the end of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IPA at 2hours | the platelet inhibition (IPA %) measured by light-transmittance aggregometry at 2 hour in CABG patients after the first dose of study drug | 2 hours after the first dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the inhibition of platelet function (IPA%) measured by LTA at 0h, 8h, 24h, 3day, and 30day after the first dose of study drug | the platelet inhibition (IPA %) measured by light-transmittance aggregometry at 0h, 8h, 24h, 3day, and 30day after the first dose of study drug | 0h, 8h, 24h, 3day, and 30day after the first dose of study drug | 
| the platelet reactivity index at 0h, 2h, 8h, 24h，3day, and 30days | the platelet reactivity index measured by corrected mean fluorescence intensities (MFIc) at 0h, 2h, 8h, 24h，3day, and 30day after the first dose of study drug in CABG patients. | 0h, 2h, 8h, 24h，3day, and 30day after the first dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CABG, antiplatelet therapy, ticagrelor