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（普遍）血液透析患者，97,000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。报告的2年和3年存活率分别只有63%和50%。在世界范围内，有近100万患者接受血液透析治疗，随着血液透析在发展中国家的可得性迅速扩大，血液透析的增长率也在不断增加。透析治疗结合高容量交换（HDF、血液滤过）可改善磷酸盐去除、B2微球蛋白去除、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降低了。然而，由于专用设备和昂贵的不可重复使用的组件，这些治疗受到限制。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，可以在血液流量为500 ml/min时去除高达90%进入透析器的毒素（尿素），与目前使用的标准透析器相比，提高了近40%。此外，我们的透析器过滤了25%的血流量（血流量为500毫升/分钟时125毫升/分钟），可以去除标准血液透析无法有效去除的中等重量毒素。DFB透析器是HDF的一种形式，但与HDF相比，具有改进的小分子去除。此外，DFB透析器的治疗并不局限于特定的设备，所有患者都可以使用，以降低发病率，降低成本并最终提高生存率。这个第二阶段的提案将测试DFB透析器的最终生产原型。AIM 1将评估间隙和过滤特性。AIM 2将测试交换液的微生物液质量。AIM 3将评估溶血和凝血的动物试验。最后，AIM 4将通过进行两项平行临床试验来证明安全性和有效性。使用的方案，包括患者数量，遵循FDA和ISO关于高渗透性和血液透析的指导方针。这项I期研究的目标是对DFB透析器进行必要的测试，以获得FDA和国际监管部门的营销批准。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结合在全球范围内推广DFB透析器。我们预计到第10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疗法相比，透析器在清除（去除）中小型重量范围内的毒素方面具有优势。每年在美国接受透析治疗的35万名患者以及全球100多万名患者都将受益于这项创新技术。

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.