Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis

NCT ID: NCT01560780

Last Updated: 2019-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-01
• Study Completion Date: 2018-05-31

Brief Summary

This is a randomized-controlled clinical trial that will randomize 120 patients undergoing clinically-indicated coronary artery bypass graft surgery to prasugrel at a dose of 10 mg daily or matching placebo for 12 months, starting at the time of hospital dismissal from surgery. The primary goal of the study is to determine whether prasugrel administration will prevent thrombus (clot) formation within a saphenous vein graft at 12 months, as examined by optical coherence tomography.

Detailed Description

Aortocoronary saphenous vein graft failure is common and is associated with high morbidity and mortality. Thrombus formation plays a critical role in early saphenous vein graft occlusion and may predispose to subsequent atherosclerosis formation. Optical coherence tomography is a novel, high-resolution, intravascular imaging technique that can reliably identify thrombus. Based on the findings of earlier VA Cooperative Studies, aspirin significantly reduces the incidence of early saphenous vein graft failure and is currently used in nearly all patients undergoing coronary bypass graft surgery. Administration of clopidogrel for improving early saphenous vein graft patency has provided conflicting results in small randomized studies. Prasugrel is a novel thienopyridine that provides more rapid, consistent, and intense platelet inhibition than clopidogrel. However, in patients who undergo coronary artery bypass graft surgery, it remains unknown whether prasugrel may decrease thrombus formation in saphenous vein grafts during the first postoperative year, and whether this will result in less saphenous vein graft wall thickening, less lipid deposition in the saphenous vein graft wall and fewer clinical events without increasing the risk for severe bleeding.

Hypothesis: The investigators hypothesize that in patients undergoing clinically-indicated coronary artery bypass graft surgery, administration of prasugrel starting at dismissal from the index coronary bypass graft surgery hospitalization will result in lower prevalence of thrombus formation in a target SVG, as assessed by optical coherence tomography performed 12 months post surgery compared to placebo, with similar incidence of major bleeding.

This is a phase III, single-center, double-blind trial that will randomize 120 patients undergoing clinically-indicated coronary artery bypass graft surgery to prasugrel at a dose of 10 mg daily or matching placebo for 12 months, starting at the time of hospital dismissal from surgery. All patients will receive aspirin. Coronary angiography, optical coherence tomography, intravascular ultrasonography, and near-infrared spectroscopy of one target saphenous vein graft will be performed at 12 months to determine whether compared to placebo, administration of prasugrel will result in:

1. Reduction of the prevalence of intragraft thrombus at 12-month follow-up optical coherence tomography imaging (primary efficacy endpoint)

2. Similar incidence of severe bleeding using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria (primary safety endpoint)

3. Reduction in the incidence of angiographic SVG failure (defined as 75% SVG diameter stenosis in at least one SVG); reduction in total and normalized total target saphenous vein graft atheroma volume, as assessed by intravascular ultrasonography; and reduction of saphenous vein graft lipid core burden index, as assessed at near-infrared intracoronary spectroscopy at 12-month follow-up cardiac catheterization (secondary endpoints)

4. Reduction of major adverse cardiac events, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoints)

Conditions

Coronary Artery Bypass

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1: Prasugrel

prasugrel 10 mg by mouth daily

Group Type: EXPERIMENTAL

Prasugrel

Intervention Type: DRUG

one 10 mg tablet by mouth daily

Arm 2: Placebo

placebo by mouth once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo similar in appearance to prasugrel

Interventions

Prasugrel

one 10 mg tablet by mouth daily

Intervention Type: DRUG

Placebo

placebo similar in appearance to prasugrel

Intervention Type: DRUG

Other Intervention Names

Effient

Eligibility Criteria

Inclusion Criteria

• Age 18 years or greater
• Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
• Undergoing clinically-indicated coronary artery bypass graft surgery

Exclusion Criteria

• Known allergy to aspirin or prasugrel
• Need for concomitant cardiac procedure, such as valve repair or replacement
• Increased risk of bleeding, including need for warfarin or dabigatran administration
• Positive pregnancy test or breast-feeding
• Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
• Serum creatinine > 2.5 mg/dL
• Severe peripheral arterial disease limiting vascular access
• Prior stroke or transient ischemic attack
• Weight <60 kg or age >75 years
• Multiple distal SVG anastomoses
• Postoperative complications prolonging hospitalization

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shuaib M. Abdullah, MD

Role: PRINCIPAL_INVESTIGATOR

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Locations

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, United States

Jesse Brown VA Medical Center Community-Based Outpatient Clinic Lake Side Divison, Chicago, IL

Chicago, Illinois, United States

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CLIN-007-11F

Identifier Type: -

Identifier Source: org_study_id