Clinical trial NCT00228423: Trial of Clopidogrel After Surgery for Coronary Artery Disease (CASCADE Trial)
Official title: Clopidogrel After Surgery for Coronary Artery Disease (CASCADE Trial): Does Clopidogrel Prevent Saphenous Vein Graft Disease After Coronary Bypass?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atherosclerosis
Keywords: Saphenous vein
Intimal hyperplasia
Coronary artery bypass graft surgery
Antiplatelet therapy
Clopidogrel
Saphenous vein graft disease
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Bristol-Myers Squibb
First posted: 2005-09-28
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Vein Graft Intimal Area
timeFrame: One year following surgery
Secondary outcomes:
measure: Vein Graft Angiographic Patency
timeFrame: One year following surgery
measure: Incidence of Major Adverse Coronary Events Within One Year Following Surgery
timeFrame: 1 year
measure: Incidence of Major Bleeding Events Within One Year Following Surgery
timeFrame: 1 year
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Marc Ruel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Alexander Kulik, MD
role: STUDY_DIRECTOR
affiliation: Ottawa Heart Institute Research Corporation
name: Michel Le May, MD
role: STUDY_DIRECTOR
affiliation: Ottawa Heart Institute Research Corporation
name: George A Wells, PhD
role: STUDY_DIRECTOR
affiliation: Ottawa Heart Institute Research Corporation
name: Thierry G Mesana, MD, PhD
role: STUDY_DIRECTOR
References:
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citation: Kulik A, Le May M, Wells GA, Mesana TG, Ruel M. The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]. Curr Control Trials Cardiovasc Med. 2005 Oct 11;6(1):15. doi: 10.1186/1468-6708-6-15.
citation: Kulik A, Le May MR, Voisine P, Tardif JC, Delarochelliere R, Naidoo S, Wells GA, Mesana TG, Ruel M. Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial. Circulation. 2010 Dec 21;122(25):2680-7. doi: 10.1161/CIRCULATIONAHA.110.978007. Epub 2010 Dec 6.
citation: Kulik A, Voisine P, Mathieu P, Masters RG, Mesana TG, Le May MR, Ruel M. Statin therapy and saphenous vein graft disease after coronary bypass surgery: analysis from the CASCADE randomized trial. Ann Thorac Surg. 2011 Oct;92(4):1284-90; discussion 1290-1. doi: 10.1016/j.athoracsur.2011.04.107.
citation: Une D, Kulik A, Voisine P, Le May M, Ruel M. Correlates of saphenous vein graft hyperplasia and occlusion 1 year after coronary artery bypass grafting: analysis from the CASCADE randomized trial. Circulation. 2013 Sep 10;128(11 Suppl 1):S213-8. doi: 10.1161/CIRCULATIONAHA.112.000328.
citation: Une D, Al-Atassi T, Kulik A, Voisine P, Le May M, Ruel M. Impact of clopidogrel plus aspirin versus aspirin alone on the progression of native coronary artery disease after bypass surgery: analysis from the Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) randomized trial. Circulation. 2014 Sep 9;130(11 Suppl 1):S12-8. doi: 10.1161/CIRCULATIONAHA.113.008227.
citation: Hage A, Voisine P, Erthal F, Larose E, Glineur D, Chow B, Tremblay H, Fortier J, Ko G, Une D, Farkouh M, Mesana TG, LeMay M, Kulik A, Ruel M. Eight-year follow-up of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial. J Thorac Cardiovasc Surg. 2018 Jan;155(1):212-222.e2. doi: 10.1016/j.jtcvs.2017.06.039. Epub 2017 Jun 24.