Hemodialysis Vascular Access Clinical Trials Consortium

描述(申请人提供)：可靠的血管通路是提供足够的血液透析的关键要求。两种类型的永久性血管通路是动静脉(A-V)瘘和A-V移植物。移植物在静脉吻合口处易发生肌内膜增生，导致再狭窄和血栓形成。预防肌内膜增生的药物干预可能会减少移植物狭窄和血栓形成的频率，从而减少昂贵干预的需要，并延长其透析的长期开放时间。体外研究表明，抗血小板药物潘生丁可抑制血管平滑肌细胞的增殖。此外，一项单中心、随机、双盲临床试验观察到，双嘧达莫(加或不加阿司匹林)可将移植物血栓形成的频率降低40%-50%。对于血管通路，瘘管比移植物更受欢迎。一旦瘘管成功地用于透析，与移植物相比，它们需要的干预要少得多，才能实现长期通畅。然而，瘘管有很高的原发失败率(约35%)(永远无法用于透析的瘘管)。原发衰竭可能是由于早期血栓形成或未成熟。早期瘘管血栓形成可能是手术后血管损伤引起的高凝状态所致。因此，使用抗血小板药物的短期治疗可能会减少早期瘘管血栓形成的频率。小规模的初步研究表明，噻氯匹定、磺胺吡喃和阿司匹林可以预防早期瘘管血栓形成。这项拟议的研究将包括两项平行的前瞻性、随机、双盲、多中心调查。在第一项试验中，接受新的动-静脉移植物的慢性肾脏疾病患者将被随机分为接受Aggrenox(长效双嘧达莫+低剂量阿司匹林)或安慰剂的患者，每天两次。主要终点将是无干预的移植物存活率。第二项研究将随机选择接受新瘘管治疗的患者，每天接受一次氯吡格雷75 mg或安慰剂治疗。主要终点是6周内瘘管血栓形成，次要终点是6个月内成功使用瘘管进行透析的能力。

DESCRIPTION (provided by applicant): A reliable vascular access is a critical requirement for providing adequate hemodialysis. The two types of permanent vascular access are an arterio-venous (A-V) fistula and an A-V graft. Grafts are prone to developing myointimal hyperplasia at the venous anastomosis, which leads to recurrent stenosis and thrombosis. A pharmacologic intervention that prevents myointimal hyperplasia might decrease the frequency of graft stenosis and thrombosis, thereby reducing the need for costly interventions and prolonging their long-term patency for dialysis. In vitro studies have demonstrated that the anti-platelet agent dipyridamole inhibits vascular smooth cell proliferation. Moreover, a single-center, randomized, double- blinded clinical trial observed that dipyridamole (with or without aspirin) decreased the frequency of graft thrombosis by 40-50%. Fistulas are preferred to grafts for vascular access. Once fistulas are successfully used for dialysis, they require far fewer interventions to achieve long-term patency, as compared with grafts. However, fistulas have a high (approximately 35%) rate of primary failure (fistulas that are never usable for dialysis). Primary failure may be due to early thrombosis or failure to mature. Early fistula thrombosis may result from a hyper-coagulable state due to vascular injury following surgery. For this reason, short-term treatment with an anti-platelet agent may reduce the frequency of early fistula thrombosis. Small pilot studies have shown that ticlopidine, sulfinpyrazone, and aspirin may prevent early fistula thrombosis. The proposed study will consist of 2 parallel prospective, randomized, double-blinded, multi-center investigations. In the first one, chronic kidney disease patients receiving a new A-V graft will be randomized to receive either Aggrenox (long-acting dipyridamole + low-dose aspirin) or placebo twice daily. The primary endpoint will be intervention-free graft survival. The second study will randomize patients receiving a new fistula to receive either clopidogrel 75 mg or placebo once daily. The primary endpoint will be fistula thrombosis within 6 weeks, and the secondary endpoint will be the ability to use the fistula successfully for dialysis within 6 months.