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

Atherosclerosis Clinical Trial

— CASCADE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00228423
• Other study ID #: UOHI 2006-111
• Status: Completed
• Phase: Phase 2
• Start date: May 2006
• Est. completion date: July 2009

Study information

• Verified date: March 2021
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: July 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Clopidogrel 75 mg daily
Daily dose of 75 mg Clopidogrel
• water pill daily
Daily dose of water pill (placebo)

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Bristol-Myers Squibb, Sanofi

Country where clinical trial is conducted

Canada, 

References & Publications (15)

Bhatt DL, Chew DP, Hirsch AT, Ringleb PA, Hacke W, Topol EJ. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation. 2001 Jan 23;103(3):363-8. — View Citation

Cadroy Y, Bossavy JP, Thalamas C, Sagnard L, Sakariassen K, Boneu B. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation. 2000 Jun 20;101(24):2823-8. — View Citation

Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol. 1996 Sep;28(3):616-26. — View Citation

Fox KA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, Yusuf S; Clopidogrel in Unstable angina to prevent Recurrent ischemic Events Trial. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation. 2004 Sep 7;110(10):1202-8. Epub 2004 Aug 16. — View Citation

Harker LA, Marzec UM, Kelly AB, Chronos NR, Sundell IB, Hanson SR, Herbert JM. Clopidogrel inhibition of stent, graft, and vascular thrombogenesis with antithrombotic enhancement by aspirin in nonhuman primates. Circulation. 1998 Dec 1;98(22):2461-9. — View Citation

Herbert JM, Dol F, Bernat A, Falotico R, Lalé A, Savi P. The antiaggregating and antithrombotic activity of clopidogrel is potentiated by aspirin in several experimental models in the rabbit. Thromb Haemost. 1998 Sep;80(3):512-8. — View Citation

Herbert JM, Tissinier A, Defreyn G, Maffrand JP. Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits. Arterioscler Thromb. 1993 Aug;13(8):1171-9. — View Citation

Hermann A, Weber AA, Schrör K. Clopidogrel inhibits platelet adhesion and platelet-dependent mitogenesis in vascular smooth muscle cells. Thromb Res. 2002 Jan 15;105(2):173-5. — View Citation

Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW. Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest. 1992 Feb;89(2):507-11. — View 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 — View 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) Tr — View 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. — View Citation

Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation. 1998 Mar 10;97(9):916-31. Review. — View 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 Di — View 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: 10.11 — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Vein Graft Angiographic Patency	Postoperative angiogram 12 months post-CABG	One year following surgery
Secondary	Incidence of Major Adverse Coronary Events Within One Year Following Surgery		1 year
Secondary	Incidence of Major Bleeding Events Within One Year Following Surgery		1 year

External Links

•   University of Ottawa Heart Institute Website