Safety and efficacy evaluation of the double fiber bundle dialyzer

描述（由申请人提供）：USRDS（美国肾衰竭患者登记处）指出，在2005年底，美国有314，000例（流行）血液透析患者，有97，000名新诊断（事件）终末期肾病（ESRD）患者接受血液透析。不幸的是，血液透析患者的一年生存率为78%，在过去十年中没有改善。报道的2年和3年生存率分别仅为63%和50%。全世界有近1，000，000名患者接受血液透析治疗，随着发展中国家血液透析的可获得性迅速扩大，血液透析的增长率不断增加。透析治疗联合高容量交换（HDF，血液透析滤过）改善了磷酸盐清除、B2微球蛋白清除、血流动力学不稳定、贫血、营养参数和透析相关淀粉样变性。最重要的是，一些研究表明死亡率下降。然而，由于专用设备和昂贵的不可重复使用的组件，这些治疗是有限的。在我们成功的I期资助期间，我们开发了一种创新的双纤维束（DFB）透析器，可清除高达90%的毒素（尿素），这些毒素以500 ml/min的血流量进入透析器，与目前使用的标准透析器相比，改进了近40%。此外，我们的透析器过滤了25%的血流量（在500 ml/min的血流量下为125 ml/min），可清除标准血液透析无法有效清除的中等重量毒素。DFB透析器是HDF的一种形式，但与HDF相比，其小分子清除率有所改善。此外，使用DFB透析器进行治疗并不局限于特定的设备，所有患者都可以使用这种治疗策略，以改善发病率、降低成本并最终提高生存率。本阶段II提案将测试DFB透析器的最终生产原型。AIM 1将评价清除率和过滤特性。AIM 2将测试交换液的微生物液体质量。AIM 3将评估溶血和凝血的动物试验。最后，AIM 4将通过两项平行临床试验证明其安全性和有效性。使用的方案（包括患者数量）遵循FDA和ISO高渗透性和血液透析滤过透析器指南。本I期研究的目标是对DFB透析器进行所需的试验，以获得FDA和国际监管上市批准。在第一阶段研究成功后，我们计划通过直销和当地经销商的组合在全球销售DFB透析器。我们预计到第十年，市场渗透率约为11%，收入为1.5亿美元。公共卫生相关性：本项目将测试双纤维束透析器的安全性和有效性。与目前可用的任何透析器或治疗相比，该透析器在清除（清除）小重量和中等重量范围的毒素方面具有上级优势。美国每年接受透析的35万名患者和世界上100多万名患者都将从这项创新技术中受益。

DESCRIPTION (provided by applicant): The USRDS (US Registry of Kidney Failure Patients) states that at the end of 2005, there were 314,000 (prevalent) hemodialysis patients in the U.S., with 97,000 newly diagnosed (incident) end stage renal disease (ESRD) patients receiving hemodialysis. Unfortunately, the one year survival for hemodialysis patients is 78%, which has not improved in the last decade. The reported two and three year survivals are only 63% and 50%, respectively. Worldwide, there are nearly 1,000,000 patients receiving hemodialysis therapy, with an increasing hemodialysis growth rate as the availability of hemodialysis in developing countries expands rapidly. Dialysis treatments coupled with high volume exchange (HDF, hemodiafiltration) have resulted in improve phosphate removal, B2 microglobulin removal, hemodynamic instability, anemia, nutritional parameters, and dialysis related amyloidosis. Most importantly, several studies have shown decreased mortality rates. These treatments, however, are limited due to specialized equipment and expensive non reusable components. During our successful Phase I Grant, we developed an innovative double fiber bundle (DFB) dialyzer that removed up to 90% of the toxins (urea) that entered the dialyzer at blood flows of 500 ml/min, an improvement of nearly 40% compared to standard dialyzers used today. In addition, our dialyzer had filtration of 25% of blood flow (125 ml/min at blood flows of 500 ml/min) which removes the middle weight toxins that standard hemodialysis removes inefficiently. The DFB dialyzer is a form of HDF, but with improved small molecule removal compared with HDF. In addition, treatment with the DFB dialyzer is not restricted to specific equipment and will be available to all patients with the strategy to improve morbidity, reduce costs and ultimately improve survival. This Phase II proposal will test the final production prototype of the DFB Dialyzer. AIM 1 will evaluate clearance and filtration characteristics. AIM 2 will test the microbiologic fluid quality of the exchanged fluid. AIM 3 will assess animal trials for hemolysis and clotting. Finally, AIM 4 will prove safety and efficacy by performing two parallel clinical trials. The protocols to be used, including the number of patients, follow the FDA and ISO guidelines for high permeability and hemodiafiltration dialyzers. The goal of this Phase I study is to perform the required testing of the DFB Dialyzer to obtain FDA and international regulatory marketing approval. After successful Phase I studies, we plan to market the DFB dialyzer throughout the world in a combination of direct sales and local distributors. We expect market penetration of approximately 11% and revenues of $150,000,000 by year ten (10). PUBLIC HEALTH RELEVANCE: This project will test the safety and efficacy of a double fiber bundle dialyzer. The dialyzer is superior in clearance (removal) of toxins of both small and middle weight range compared to any dialyzer or therapy currently available. The 350,000 patients who receive dialysis every year in the US and the 1,000,000 plus in the world would all benefit from this innovative technology.