Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis
Condition: Coronary Artery Bypass
MeSH terms: Thrombosis
Study type: Interventional
Phase: Phase 3

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)
    

Intervention name(s): Prasugrel; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): one 10 mg tablet by mouth daily; placebo similar in appearance to prasugrel
Other intervention name(s): Effient
Intervention MeSH terms: Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Coronary Artery Bypass; thrombosis; prasugrel