NCT00228423

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
113

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started May 2006

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 26, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 28, 2005

Completed
7 months until next milestone

Study Start

First participant enrolled

May 1, 2006

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2009

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2009

Completed
11.8 years until next milestone

Results Posted

Study results publicly available

April 27, 2021

Completed
Last Updated

April 27, 2021

Status Verified

March 1, 2021

Enrollment Period

3.1 years

First QC Date

September 26, 2005

Results QC Date

March 30, 2021

Last Update Submit

March 30, 2021

Conditions

Atherosclerosis

Keywords

Saphenous veinIntimal hyperplasiaCoronary artery bypass graft surgeryAntiplatelet therapyClopidogrelSaphenous vein graft disease

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Vein Graft Angiographic Patency

    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

Study Arms (2)

75mg Clopidogrel

ACTIVE COMPARATOR

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

Drug: Clopidogrel 75 mg daily

Placebo

PLACEBO COMPARATOR

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

Drug: water pill daily

Interventions

Clopidogrel 75 mg dailyDRUG

Daily dose of 75 mg Clopidogrel

75mg Clopidogrel
water pill dailyDRUG

Daily dose of water pill (placebo)

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients undergoing primary multi-vessel CABG with at least two saphenous vein grafts, with or without the use of cardiopulmonary bypass.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (16)

  • 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. doi: 10.1016/0735-1097(96)00206-9.

    PMID: 8772748BACKGROUND

  • Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation. 1998 Mar 10;97(9):916-31. doi: 10.1161/01.cir.97.9.916.

    PMID: 9521341BACKGROUND

  • 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. doi: 10.1172/JCI115613.

    PMID: 1531345BACKGROUND

  • Herbert JM, Dol F, Bernat A, Falotico R, Lale 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.

    PMID: 9759636BACKGROUND

  • 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. doi: 10.1161/01.atv.13.8.1171.

    PMID: 8343491BACKGROUND

  • Hermann A, Weber AA, Schror K. Clopidogrel inhibits platelet adhesion and platelet-dependent mitogenesis in vascular smooth muscle cells. Thromb Res. 2002 Jan 15;105(2):173-5. doi: 10.1016/s0049-3848(01)00403-0. No abstract available.

    PMID: 11958809BACKGROUND

  • 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. doi: 10.1161/01.cir.98.22.2461.

    PMID: 9832493BACKGROUND

  • 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. doi: 10.1161/01.cir.101.24.2823.

    PMID: 10859288BACKGROUND

  • 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. doi: 10.1161/01.cir.103.3.363.

    PMID: 11157686BACKGROUND

  • 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. doi: 10.1161/01.CIR.0000140675.85342.1B. Epub 2004 Aug 16.

    PMID: 15313956BACKGROUND

  • 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.

    PMID: 16219100RESULT

  • 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.

    PMID: 21135365RESULT

  • 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.

    PMID: 21958773RESULT

  • 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.

    PMID: 24030409RESULT

  • 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.

    PMID: 25200049RESULT

  • 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.

    PMID: 28734623DERIVED

Related Links

MeSH Terms

Conditions

Atherosclerosis

Interventions

ClopidogrelWater

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

TiclopidineThienopyridinesThiophenesSulfur CompoundsOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHydroxidesAlkaliesInorganic ChemicalsAnionsIonsElectrolytesOxidesOxygen Compounds

Results Point of Contact

Title
Dr. Marc Ruel
Organization
University Of Ottawa Heart Institute
mruel@ottawaheart.ca

Study Officials

  • Marc Ruel, MD, MPH

    Ottawa Heart Institute Research Corporation

    PRINCIPAL INVESTIGATOR

  • Alexander Kulik, MD

    Ottawa Heart Institute Research Corporation

    STUDY DIRECTOR

  • Michel Le May, MD

    Ottawa Heart Institute Research Corporation

    STUDY DIRECTOR

  • George A Wells, PhD

    Ottawa Heart Institute Research Corporation

    STUDY DIRECTOR

  • Thierry G Mesana, MD, PhD

    Ottawa Heart Institute Research Corporation

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2005

First Posted

September 28, 2005

Study Start

May 1, 2006

Primary Completion

June 1, 2009

Study Completion

July 1, 2009

Last Updated

April 27, 2021

Results First Posted

April 27, 2021

Record last verified: 2021-03

Locations

CA(1)