Prasugrel for prevention of early saphenous vein graft thrombosis

普拉格雷预防早期大隐静脉移植物血栓形成

• 批准号: 8698401
• 负责人: Emmanouil Brilakis
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698401
• 关键词: Alteplase; Arterial Fatty Streak; Aspirin; Atherosclerosis; Blood Platelets; Bypass; Caliber; Cardiac; Cardiac Catheterization Procedures; Cessation of life; Clinical; Conflict (Psychology); Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary artery; Deposition; Dose; Double-Blind Method; Event; Failure; Healthcare; Hemorrhage; Hospitalization; Hospitals; Image; Imaging Techniques; Incidence; Intravascular Ultrasonography; Lipids; Low Prevalence; Morbidity - disease rate; Near-Infrared Spectroscopy; Operative Surgical Procedures; Optical Coherence Tomography; Patients; Phase; Placebos; Play; Postoperative Period; Prevalence; Prevention; Randomized; Risk; Role; Safety; Saphenous Vein; Spectrum Analysis; Stenosis; Streptokinase; Thrombosis; Thrombus; Time; Veterans; acute coronary syndrome; base; clopidogrel; cooperative study; follow-up; graft failure; improved; indexing; mortality; novel; prevent; thienopyridine

DESCRIPTION (provided by applicant): Early aortocoronary saphenous vein bypass graft (SVG) failure is common and is associated with high morbidity and mortality. Aspirin significantly reduces the incidence of early saphenous vein graft failure, whereas clopidogrel use 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, leading to 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. We 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. We propose 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. The specific objectives of the proposed study are to determine whether compared to placebo, prasugrel administration 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 of total and normalized total target saphenous vein graft atheroma volume and reduction of saphenous vein graft lipid core burden index as assessed by near-infrared intracoronary spectroscopy at 12-month follow-up saphenous vein graft imaging (secondary endpoints); and (4) reduction of major adverse cardiac events, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoints).

描述（由申请人提供）： 早期冠状动脉大隐静脉旁路移植术（SVG）失败是常见的，并与高发病率和死亡率相关。阿司匹林显著降低早期隐静脉移植失败的发生率，而氯吡格雷的使用在小型随机研究中提供了相互矛盾的结果。普拉格雷是一种新的噻吩并吡啶类药物，与氯吡格雷相比，其血小板抑制作用更迅速、更持久、更强。然而，在接受冠状动脉旁路移植术的患者中，尚不清楚普拉格雷是否可以在术后第一年内减少隐静脉移植物中的血栓形成，从而减少隐静脉移植物壁增厚，减少隐静脉移植物壁中的脂质沉积和减少临床事件，而不增加严重出血的风险。我们假设，在接受临床指征的冠状动脉旁路移植术的患者中，从首次冠状动脉旁路移植术住院治疗出院时开始使用普拉格雷将导致目标SVG中血栓形成的患病率较低，通过术后12个月进行的光学相干断层扫描评估，与安慰剂相比，大出血的发生率相似。我们提出了一项III期、单中心、双盲试验，将120例接受临床指征的冠状动脉旁路移植术的患者随机分为普拉格雷组或安慰剂组，剂量为每日10 mg，持续12个月，从手术出院时开始。所有患者都将服用阿司匹林。将在12个月时对一根目标隐静脉移植物进行冠状动脉血管造影、光学相干断层扫描、血管内超声检查和近红外光谱检查。本研究的具体目的是确定与安慰剂相比，普拉格雷给药是否会导致：（1）12个月随访光学相干断层扫描成像时移植物内血栓的患病率降低（主要疗效终点）;（2）使用全球链激酶和t-PA治疗冠状动脉闭塞（GUSTO）标准时，严重出血的发生率相似（主要安全性终点）;（3）在12个月随访隐静脉移植物成像时通过近红外冠状动脉内光谱评估的总靶隐静脉移植物动脉粥样硬化体积和标准化总靶隐静脉移植物动脉粥样硬化体积的减少以及隐静脉移植物脂质核心负荷指数的减少（次要终点）;（4）随访期间主要不良心脏事件（定义为死亡、急性冠状动脉综合征或冠状动脉血运重建的复合事件）的减少（次要终点）。