DIPYRIDAMOLE IN VASCULAR ACCESS FOR HEMODIALYSIS

双嘧达莫在血液透析血管通路中的应用

• 批准号: 6524356
• 负责人: Jonathan Himmelfarb
• 金额: $ 27.38万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524356
• 关键词: arteriovenous shunt surgery; chemoprevention; chronic renal failure; clinical research; clinical trials; cooperative study; dipyridamole; hemodialysis; human subject; human therapy evaluation; thrombosis

The long-term objective of this proposal is to establish whether or not the use of dipyridamole is efficacious in improving the function of expanded polytetrafluoroethylene (ePTFE) grafts used for dialysis access in patients with end stage renal disease on chronic hemodialysis therapy. Currently, there are over 170,000 patients in the US on chronic hemodialysis therapy. For these patients, problems with vascular access patency have been called the "Achilles Heel" of the dialysis procedure. Furthermore, the development of ePTFE graft stenosis and thrombosis reduces the quality of delivered dialysis therapy and increases the infection risk for patients on dialysis. Maintaining vascular access patency costs approximately $7,871 per hemodialysis patient per year at risk with an estimated annual global cost of more than one billion dollars. Recent evidence suggests that in almost all cases, ePTFE graft thrombosis occurs only after the development of a stenosis either at the graft vein anastomosis or more distally in the vein. These venous stenoses occur because of a pathological process known as intimal hyperplasia. Recent evidence from a small, single-center, prospective, randomized, placebo-controlled clinical trial has suggested that dipyridamole may reduce the rate of ePTFE graft thrombosis in chronic hemodialysis patients. The mechanism of dipyridamole efficacy may be by inhibiting vascular smooth muscle cell proliferation and thereby reducing the development of intimal hyperplasia and associated venous stenoses. The specific aims of this proposal are: l) To investigate the efficacy of dipyridamole in preventing the development of anastomotic and venous stenoses in patients on chronic hemodialysis with ePTFE grafts; and 2) To investigate the efficacy of dipyridamole in preventing the development of thrombosis in patients on chronic hemodialysis with new ePTFE grafts. In order to answer the Specific Aims, the proposed study design is a randomized, prospective, double-blind, placebo-controlled, parallel group clinical trial. Patients on chronic hemodialysis therapy who require a new prosthetic ePTFE graft will be randomized to receive either dipyridamole or placebo for a period of 12 months after enrollment or until ePTFE graft failure. Enrolled patients will undergo serial monitoring of vascular access blood flow, known to be a physiologic predictor of impending vascular access failure, with clinically indicated interventions to prevent vascular access failure. The study design will test the null hypothesis that dipyridamole does not affect the development of either venous stenosis or thrombosis in new ePTFE grafts in hemodialysis patients.

这项建议的长期目标是确定在慢性血液透析治疗的终末期肾病患者中，使用双嘧达莫是否能有效改善用于透析通路的膨化聚四氟乙烯(EPTFE)移植物的功能。目前，美国有超过17万名患者正在接受慢性血液透析治疗。对于这些患者来说，血管通畅的问题被称为透析程序的“阿喀琉斯脚跟”。此外，ePTFE移植物狭窄和血栓的形成降低了提供的透析治疗的质量，并增加了透析患者的感染风险。维持血管通路通畅的成本约为每位有风险的血液透析患者每年7871美元，全球每年的成本估计超过10亿美元。最近的证据表明，在几乎所有的病例中，ePTFE移植物血栓只有在移植物静脉吻合口或更远端的静脉发生狭窄后才会发生。这些静脉狭窄的发生是由于一种称为内膜增生的病理过程。一项小型、单中心、前瞻性、随机、安慰剂对照临床试验的最新证据表明，双嘧达莫可以降低慢性血液透析患者ePTFE移植物血栓的发生率。潘生丁的作用机制可能是通过抑制血管平滑肌细胞的增殖，从而减少内膜增生和相关的静脉狭窄的发展。这项建议的具体目的是：L)观察双嘧达莫预防植入ePTFE的慢性血液透析患者发生吻合口和静脉狭窄的疗效；2)观察双嘧达莫预防植入新型ePTFE的慢性血液透析患者血栓形成的疗效。为了回答特定的目标，本研究设计为随机、前瞻性、双盲、安慰剂对照、平行组临床试验。接受慢性血液透析治疗的患者需要接受新的ePTFE假体移植，他们将随机接受双嘧达莫或安慰剂治疗，为期12个月，直到ePTFE移植失败。入选的患者将接受血管通路血流的连续监测，这被认为是即将发生的血管通路失败的生理学预测指标，并采用临床指示的干预措施来防止血管通路失败。这项研究设计将检验双嘧达莫不影响血液透析患者新的ePTFE移植物中静脉狭窄或血栓形成的无效假设。