Clinical trial NCT01560780: Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis
Official title: Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronary Artery Bypass
Keywords: Coronary Artery Bypass
thrombosis
prasugrel
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2012-03-22
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: Prevalence of Intragraft Thrombus at 12-month Follow-up Optical Coherence Tomography Imaging
timeFrame: 12 months
Secondary outcomes:
measure: Number of Patients With Severe Bleeding Using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) Criteria
timeFrame: 12 months
measure: Number of Patients With Angiographic Saphenous Vein Graft Failure
timeFrame: 12 months
measure: Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography
timeFrame: 12 months
measure: Saphenous Vein Graft Lipid Core Burden Index, as Assessed at Near-infrared Intracoronary Spectroscopy
timeFrame: 12 months
measure: Major Adverse Cardiac Events, Defined as the Composite of Death, Acute Coronary Syndrome, or Coronary Revascularization) During Follow-up
timeFrame: 12 months
measure: Normalized Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography
timeFrame: 12 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco VA Medical Center, San Francisco, CA
state: California
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System, Gainesville, FL
state: Florida
city: Chicago
country: United States
facility: Jesse Brown VA Medical Center Community-Based Outpatient Clinic Lake Side Divison, Chicago, IL
state: Illinois
city: Dallas
country: United States
facility: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
state: Texas
Study officials:
affiliation: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
name: Shuaib M. Abdullah, MD
role: PRINCIPAL_INVESTIGATOR
References: