Hemodialysis Vascular Access Clinical Trials Consortium

描述（由申请人提供）：可靠的血管通道是提供充分血液透析的关键要求。永久性血管通路的两种类型是动静脉（A-V）瘘和A-V移植物。移植物易在静脉吻合处发生肌内膜增生，导致血管狭窄和血栓复发。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，从而减少昂贵的干预需求并延长其长期透析通畅。体外研究表明，抗血小板药物双嘧达莫抑制血管平滑细胞增殖。此外，一项单中心、随机、双盲临床试验发现，双嘧达莫（联合或不联合阿司匹林）可使移植物血栓形成的频率降低40-50%。对于血管通道，瘘管比移植物更可取。一旦瘘成功地用于透析，与移植相比，它们需要更少的干预来实现长期通畅。然而，瘘管的原发性失败率很高（约35%）（瘘管不能用于透析）。原发性衰竭可能是由于早期血栓形成或未成熟所致。早期瘘管血栓形成可能是由于手术后血管损伤引起的高凝状态。因此，短期使用抗血小板药物治疗可以减少早期瘘管血栓形成的频率。小型试点研究表明噻氯匹定、磺胺吡嗪和阿司匹林可以预防早期瘘管血栓形成。该研究将包括2项平行、前瞻性、随机、双盲、多中心研究。在第一项研究中，接受新的a - v移植的慢性肾病患者将被随机分配接受每日两次的Aggrenox（长效双嘧达莫+低剂量阿司匹林）或安慰剂。主要终点将是无干预的移植物存活。第二项研究将随机分配接受新瘘管的患者，每天一次接受氯吡格雷75mg或安慰剂。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.