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

March 30, 2021 updated by: Ottawa Heart Institute Research Corporation

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

113

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4W7
        • University of Ottawa Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Heart Institute Research Corporation

Collaborators

Bristol-Myers Squibb
Sanofi

Investigators

  • Study Director: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (ACTUAL)

June 1, 2009

Study Completion (ACTUAL)

July 1, 2009

Study Registration Dates

First Submitted

September 26, 2005

First Submitted That Met QC Criteria

September 26, 2005

First Posted (ESTIMATE)

September 28, 2005

Study Record Updates

Last Update Posted (ACTUAL)

April 27, 2021

Last Update Submitted That Met QC Criteria

March 30, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UOHI 2006-111

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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