Preoperative Aspirin and Postoperative Antiplatelets in Coronary Artery Bypass Grafting: The PAPA CABG Study

Sponsor

Hamilton Health Sciences Corporation (Other)

Overall Status

Completed

CT.gov ID

NCT00330772

Collaborator

Bristol-Myers Squibb (Industry)

150

Enrollment

Location

Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Main Research Question(s):

What is the effect of continuing aspirin until the time of coronary artery bypass graft surgery and of adding clopidogrel to aspirin after coronary artery bypass graft surgery for preventing blockage of coronary grafts, heart attack, stroke, and death? To reliably answer this question requires a large randomised trial. Before applying for a major grant from the Canadian Institute for Health Research to do the large study we would like to perform a small pilot study of 150 patients to demonstrate that it is feasible to recruit patients and to use a new test called "CT angiography" to determine whether the bypass grafts are still working or have become blocked.

(ii) Why is this research important? Coronary artery bypass surgery has made a very important contribution to improving the health and survival of patients with advanced coronary artery disease but still has many problems. One in 10 patients experiences a heart attack at the time of surgery, 1 in 20 experiences a heart attack, stroke, or death during hospitalization, and 1 in 4 patients has at least 1 blocked graft within 1 year of surgery. Antiplatelet drugs such as aspirin and clopidogrel are effective for preventing heart attacks, strokes and deaths but aspirin is usually stopped before coronary artery bypass graft surgery because of concerns about increasing the risk of bleeding. The effectiveness of the combination of clopidogrel and aspirin after surgery has not been evaluated. Our pilot study will provide key information about feasibility that will help us to design and perform a large definitive study in the future.

(iii) What is being studied? We will be looking at blood flow in bypass grafts as well as the occurrence of heart attack, stroke, and death. For safety we will be looking at bleeding, transfusion, and need for further surgery because of bleeding. We will also perform laboratory tests of platelet function to measure and compare the effect of the study treatments to prevent blood clots from forming.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Coronary Artery Bypass Grafting	Drug: Aspirin Drug: Clopidogrel	Phase 3

Detailed Description

BACKGROUND: Platelets play a central role in the pathogenesis of ischemic complications (coronary artery bypass graft occlusion, myocardial infarction, stroke) following CABG surgery. Aspirin and clopidogrel used alone or in combination are effective for preventing ischemic complications in a broad range of high risk patients. However aspirin is usually discontinued before CABG surgery because of concerns about bleeding while the combination of aspirin and clopidogrel has not been evaluated for preventing ischemic complications after CABG surgery.

OBJECTIVES: The overall objectives of our research are to compare the effectiveness and safety of aspirin vs placebo before bypass surgery, and clopidogrel plus aspirin vs aspirin alone after surgery, on:

blockage of coronary artery bypass grafts, MI, stroke, or death at 30 days
bleeding and need for transfusion after surgery The specific objective of the present pilot study is to demonstrate the feasibility of recruiting patients undergoing CABG surgery into this study and of performing CT angiography at 30 days to determine graft patency. We will also measure the effect of different antiplatelet treatments on platelet function and blood markers of systemic inflammation during the first 48 hours after surgery.

DESIGN: This is a 2x2 factorial study of 150 elective CABG patients who will be randomized to receive low dose aspirin (81mg/d) or placebo for 5 days prior to surgery and aspirin 325mg loading dose followed by 81 mg/d plus clopidogrel 75 mg/d versus aspirin 81 mg/d and placebo post operatively.

OUTCOME: graft patency measured by CT angiography, MI, stroke, death, bleeding, transfusion requirement, need for re-exploration surgery, and laboratory measures of platelet function and aspirin resistance (including 11-dehydro thromboxane B2).

SAMPLE SIZE: This is a pilot study designed primarily to demonstrate feasibility. We propose to recruit a total of 150 patients over a 12 month period (2-4 per week).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Pilot Study of Preoperative Aspirin and Postoperative Clopidogrel's Effects on Graft Patency and Cardiac Events in Coronary Artery Bypass Surgery

Study Start Date :

Jul 1, 2006

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Outcome Measures

Primary Outcome Measures

Graft patency, MI, Death, Stroke []

Secondary Outcome Measures

Bleeding, transfusion, re-exploration, Platelet function tests []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients 18 years of age or older
Undergoing on-pump, elective coronary artery bypass grafting with at least 2 free grafts
Patient able to give informed consent

Exclusion Criteria:

planned date of surgery is <5 days from planned recruitment date
patient has clear indication for anticoagulation (eg. mechanical heart valve, atrial fibrillation) or ADP receptor antagonist (eg. drug-eluting stent)
allergy to or intolerance of aspirin or clopidogrel
history of bleeding diathesis, significant GI bleed, ICH, or liver failure
Patient has known renal failure or contraindication for Cardiac CT Angio
Patient has had previous cardiac surgery