Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 4
- 主要终点
- Prevalence of Intragraft Thrombus at 12-month Follow-up Optical Coherence Tomography Imaging
研究概览
简要总结
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.
详细描述
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:
- Reduction of the prevalence of intragraft thrombus at 12-month follow-up optical coherence tomography imaging (primary efficacy endpoint)
- Similar incidence of severe bleeding using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria (primary safety endpoint)
- 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)
- Reduction of major adverse cardiac events, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoints)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm 1: Prasugrel
prasugrel 10 mg by mouth daily
干预措施: Prasugrel (Drug)
Arm 2: Placebo
placebo by mouth once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Prevalence of Intragraft Thrombus at 12-month Follow-up Optical Coherence Tomography Imaging
时间窗: 12 months
Number of patients with intragraft thrombus seen at 12 month follow-up by optical coherence tomography in imaged saphenous vein graft
次要结局
- Number of Patients With Severe Bleeding Using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) Criteria(12 months)
- Number of Patients With Angiographic Saphenous Vein Graft Failure(12 months)
- Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography(12 months)
- Saphenous Vein Graft Lipid Core Burden Index, as Assessed at Near-infrared Intracoronary Spectroscopy(12 months)
- Major Adverse Cardiac Events, Defined as the Composite of Death, Acute Coronary Syndrome, or Coronary Revascularization) During Follow-up(12 months)
- Normalized Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography(12 months)