Trial of Clopidogrel After Surgery for Coronary Artery Disease (CASCADE Trial)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the combination of clopidogrel with aspirin prevents the development of blockages (atherosclerosis) in vein grafts one year after coronary artery bypass surgery (CABG) compared to aspirin alone.

Detailed Description
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Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery (CABG). The process of saphenous vein intimal hyperplasia is mediated by platelet aggregation and begins just days after surgical revascularization. Subsequently, areas of intimal hyperplasia in turn develop graft atherosclerotic disease and its sequelae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following one year after CABG. Patients undergoing multi-vessel CABG and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for the duration of one year starting as soon as postoperative bleeding has been ruled out on the day of surgery. At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The study will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.

Official Title
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Clopidogrel After Surgery for Coronary Artery Disease (CASCADE Trial): Does Clopidogrel Prevent Saphenous Vein Graft Disease After Coronary Bypass?

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: Clopidogrel 75 mg daily
* Drug: water pill daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing primary multi-vessel CABG with at least two saphenous vein grafts, with or without the use of cardiopulmonary bypass. Exclusion Criteria: Emergency surgery Valve surgery Redo CABG Left ventricle ejection fraction < 25% Serum creatinine > 130 µmol/L Preoperative use of clopidogrel (with the exception of the current admission) Preoperative use of warfarin; allergy to aspirin or clopidogrel. History of cerebrovascular accident History of severe liver disease Morbid obesity Current malignancy

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 75mg Clopidogrel<br>75mg clopidogrel. 162mg ASA is also given, but is a standard-of-care post operative to cardiac surgery. | Drug: Clopidogrel 75 mg daily<br>* Daily dose of 75 mg Clopidogrel<br>|
| Placebo Comparator: Placebo<br>Water pill. 162mg ASA is also given, but is a standard-of-care post operative to cardiac surgery. | Drug: water pill daily<br>* Daily dose of water pill (placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vein Graft Intimal Area | IVUS imaging 12 months post-CABG, and the average intimal area in the proximal 40 mm of one vein graft per patient will be assessed | One year following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vein Graft Angiographic Patency | Postoperative angiogram 12 months post-CABG | One year following surgery | 
| Incidence of Major Adverse Coronary Events Within One Year Following Surgery |  | 1 year | 
| Incidence of Major Bleeding Events Within One Year Following Surgery |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Saphenous vein, Intimal hyperplasia, Coronary artery bypass graft surgery, Antiplatelet therapy, Clopidogrel, Saphenous vein graft disease