COLLABORATIVE CLINICAL TRIALS IN VASCULAR ACCESS

描述(由申请人提供)：获得血液循环对于为终末期肾病患者提供血液透析治疗至关重要。然而，血管通路失败是这些患者的发病率和护理费用的主要原因。已建立的动静脉瘘是推荐的途径，因为与移植物相比，存活时间更长，并发症更少。不幸的是，早期瘘管血栓形成频繁发生，许多瘘管不能充分发展以支持血液透析。如果不能建立瘘管，则使用动静脉移植物。虽然移植物可以更早地使用，但超过一半的移植物会在植入后一年内失效。移植物失败的原因是新生内膜增生导致狭窄和血栓形成。为了解决这些问题，透析通路联盟(DAC)设计并启动了两项独立的试验：一项针对瘘管，另一项针对移植物。这项名为“氯吡格雷预防早期房室瘘血栓形成”的瘘管试验是一项随机、双盲、安慰剂对照试验，目的是确定放置通路时服用6周的氯吡格雷是否会增加新放置的瘘管的通畅率。第二个目的是确定氯吡格雷是否增加了适合透析的瘘管的数量。1284的样本量提供了85%的能量来检测主要终点的30%的减少，即6周的瘘管开放。题为“Aggrenox预防血管狭窄”的移植物试验是一项随机、双盲、安慰剂对照试验，目的是确定以Aggrenox(也含有少量阿司匹林)形式给予的双嘧达莫是否可以预防新造移植物的门静脉狭窄和延长首次无辅助通畅。在移植血管血栓形成之前，每月测量通路的流速，以检测血流动力学上的显著狭窄。1056的样本大小提供85%的功率来检测主要终点减少25%，即主要无辅助通畅。这两项试验的登记工作于2003年1月开始，计划于2007年初结束。数据在克利夫兰诊所的数据协调中心进行整理和分析。一个外部咨询委员会监督安全性和有效性。目前的提案寻求由爱荷华州大学关联的东爱荷华州、西伊利诺伊州血管通路联盟与DAC合作继续参与，以成功完成这两项重要的试验。如果这些治疗被证明是有益的，它们将大大降低发病率，并可能降低为血液透析患者提供护理的总体成本。

DESCRIPTION (provided by applicant): Access to the circulation is essential to provide hemodialysis treatment to people with ESRD. However, vascular access failure is a major cause of morbidity and expense in care of these patients. An established arteriovenous fistula is the recommended access due to longer survival and fewer complications compared to a graft. Unfortunately early fistula thrombosis occurs frequently and many fistulas do not develop adequately to support hemodialysis. If a fistula cannot be established, an arteriovenous graft is used. Although grafts can be used earlier, over half will fail within a year of placement. The cause of graft failure is neointimal hyperplasia leading to stenosis and thrombosis. To address these problems the Dialysis Access Consortium (DAC) designed and initiated two separate trials: one for fistulas and the other for grafts. The fistula trial entitled, "Clopidogrel Prevention of Early AV Fistula Thrombosis," is a randomized double-blind placebo controlled trial to determine if 6-weeks of clopidogrel given at the time of access placement increases the patency rate of newly placed fistulas. A secondary aim is to determine if clopidogrel increases the number of fistulas that are suitable for dialysis. A sample size of 1284 provides 85% power to detect a 30% reduction in the primary endpoint, 6-week fistula patency. The graft trial entitled "Aggrenox Prevention of Access Stenosis," is a randomized double-blind placebo controlled trial to determine if dipyridamole given in the form of Aggrenox (which also contains a small amount of aspirin) can prevent access stenosis and prolong primary unassisted patency in newly constructed grafts. Monthly measurement of access flow rate is done to detect hemodynamically significant stenosis before the graft clots. A sample size of 1056 provides 85% power to detect a 25% reduction in the primary endpoint, primary unassisted patency. Enrollment into both trials began in January 2003 and is scheduled to end in early 2007. Data is collated and analyzed at the Data Coordinating Center at the Cleveland Clinic. An external advisory committee monitors safety and efficacy. The present proposal seeks to continue participation by the University of lowa-affliated Eastern Iowa Western Illinois Vascular Access Consortium in collaboration with the DAC to successfully complete these two important trials. If the treatments are proven to be beneficial, they will substantially reduce the morbidity and possibly the overall cost of providing care to hemodialysis patients.