COLLABORATIVE CLINICAL TRIALS IN VASCULAR ACCESS

描述（由申请人提供）：进入血液循环是为ESRD患者提供血液透析治疗的必要条件。然而，血管通路失败是这些患者发病率和费用的主要原因。由于与移植物相比，建立动静脉瘘的存活时间更长，并发症更少，因此推荐使用动静脉瘘。不幸的是，早期瘘管血栓经常发生，许多瘘管没有充分发展以支持血液透析。如果不能建立瘘，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的一年内失效。移植物失败的原因是内膜增生导致狭窄和血栓形成。为了解决这些问题，透析准入联盟（DAC）设计并启动了两个独立的试验：一个针对瘘管，另一个针对移植物。瘘管试验题为“氯吡格雷预防早期房内瘘血栓形成”，是一项随机双盲安慰剂对照试验，旨在确定在通道放置时给予6周氯吡格雷是否增加新放置瘘管的通畅率。第二个目的是确定氯吡格雷是否会增加适合透析的瘘管数量。1284个样本量提供了85%的能力来检测主要终点（6周瘘管通畅）减少30%。名为“Aggrenox预防通路狭窄”的移植物试验是一项随机双盲安慰剂对照试验，旨在确定以Aggrenox形式给予的双嘧达莫（也含有少量阿司匹林）是否可以预防通道狭窄并延长新建移植物的初级无辅助通畅。每月测量通道流速，以便在移植物凝块之前检测血流动力学上显著的狭窄。1056例的样本量提供了85%的能力来检测主要终点（原发性无辅助通畅）降低25%。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。本提案寻求由爱荷华大学附属的东爱荷华州西伊利诺伊州血管通道联盟与DAC合作继续参与，以成功完成这两项重要试验。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.