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

University of Ottawa Heart Institute

Status and phase: Completed; Phase 2

Conditions: Atherosclerosis

Treatments: Drug: Clopidogrel 75 mg daily; Drug: water pill daily

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00228423

UOHI 2006-111

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 113 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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113 participants in 2 patient groups, including a placebo group

75mg Clopidogrel

Active Comparator group

Description:

75mg clopidogrel. 162mg ASA is also given, but is a standard-of-care post operative to cardiac surgery.

Treatment:

Drug: Clopidogrel 75 mg daily

Placebo

Placebo Comparator group

Description:

Water pill. 162mg ASA is also given, but is a standard-of-care post operative to cardiac surgery.

Treatment:

Drug: water pill daily