Product and Regulatory Development of a Needle-Free Hemodialysis Access Port

无针血液透析接入口的产品及规范开发 项目总结 目标：SBIR第二期B期桥梁奖项目的总体目标是推动一种新的无针 血液透析接入端口进入IDE批准阶段，随后在人体试验中首次获得批准。 意义：对于美国近500,000名终末期肾病(ESRD)肾衰竭患者进行血液透析 (HD)，需要每周三次的门诊治疗，需要使用大型透析针(最多2毫米)进行插管 直径)是耗时、痛苦和令人不快的，并且使得维持可靠的血管通路部位 极具挑战性。由于已建立的永久性血管通路方法的高失败率- 动静脉瘘和动静脉移植物--超过一半的第一年血液透析患者，超过20% 从长远来看，是通过易感染的导管治疗的。频繁的住院治疗费用难以承受 医疗体系和大多数患者悲惨的生活质量。 家庭HD治疗每年为每个患者节省2万美元，可以在患者方便的时候进行，显著 改善患者健康，并具有主要的生活质量好处，使许多患者能够继续生产 就业。患者调查指出，针头厌恶是增加家庭自我治疗的最大障碍。一种新的 克服这一障碍的接入选项将鼓励增加家庭高清。 创新：以前提供钝性插管进入房室移植物管腔的经皮口设备是 功能和患者认可，但最终因出口处的感染问题而在临床和商业上失败 移植物的位置和通畅性差。Healionics已经开发出克服这些问题的技术，通过使用其 星形多孔生物材料在组织界面，使无针HD接入端口概念得以重新引入。 STAR的优化孔隙几何结构诱导了一个永久的血管化组织界面，该界面利用身体的 对细菌感染的天然防御。将STAR应用于房室移植物的外壁消除囊膜 收缩力，保持移植物管壁的弹性，防止通常的渐进式静脉末端破坏模式 新生内膜增生。止血阀设计和其他部件的改进有望 与早期的端口设备相比，进一步提高了可靠性和安全性。 方法：该项目的具体目标是：1)扩展原型开发和初步临床前测试 根据R44HL26256进行更完整的器件设计，2)进行正式的技术验证、制造流程 开发、可靠性测试和临床前研究，以及3)准备并提交成功的集成开发应用程序 食品和药物管理局。IDE的批准将使人类第一次早期可行性研究在SBIR结束后不久开始 第二阶段B项目期间，由在SBIR项目期间获得的投资资金支持。 影响：项目的成功将使高风险导管的使用显著减少，并避免 增加家庭自我照顾的主要障碍。这将大大降低肾衰竭护理的成本，并改善 ESRD患者群体中很大一部分患者的患者安全和生活质量。 V0.34

Product and Regulatory Development of a Needle-Free Hemodialysis Access Port PROJECT SUMMARY Objective: The overall objective of this SBIR Phase IIB Bridge Award project is to advance a new Needle-Free Hemodialysis Access Port to the stage of IDE approval for a subsequent first in Human study. Significance: For the nearly 500,000 End Stage Renal Disease (ESRD) kidney failure patients in the US on hemodialysis (HD), the need for thrice-weekly in-clinic treatments requiring cannulation by large dialysis needles (up to 2 mm diameter) is time consuming, painful and unpleasant and makes maintenance of a reliable vascular access site extremely challenging. As a result of high failure rates with the established permanent vascular access methods – arteriovenous (AV) fistulas and AV grafts – more than half of all first-year hemodialysis patients, and more than 20% longer term, are treated via infection-prone catheters. There are frequent hospitalizations with unsustainable costs to the healthcare system and a miserable quality of life for most patients. Home HD treatment saves $20,000 per patient year, can be done at the patient’s convenience, significantly improves patient health, and has the major quality-of-life benefit of enabling many patients to continue productive employment. Patient surveys cite needle aversion as the biggest obstacle to increased home self-treatment. A new access option that overcomes this barrier would encourage increased home HD. Innovation: Previous percutaneous port devices providing blunt cannula access to the lumen of an AV graft were functional and patient-appreciated but eventually failed clinically and commercially from infection issues at the exit site and poor patency of the grafts. Healionics has developed technologies that overcome these issues by use of its STAR porous biomaterial at tissue interfaces, enabling a reintroduction of the needle-free HD access port concept. STAR’s optimized pore geometry induces a permanently vascularized tissue interface that leverages the body’s natural defenses against bacterial infection. Application of STAR to the outside of an AV graft eliminates capsular contraction forces, preserving graft wall flexibility and preventing the usual failure mode of progressive venous-end neointimal hyperplasia. Improvements to the hemostasis valve design and other components are expected to further improve reliability and safety versus earlier port devices. Approach: Specific aims for the project are 1) extend the prototype development and initial preclinical testing done under R44HL26256 into a more complete device design, 2) conduct formal technical verification, fabrication process development, reliability testing and preclinical studies, and 3) prepare and submit a successful IDE application to the FDA. IDE approval will allow a first-in-human Early Feasibility Study to begin soon after conclusion of the SBIR Phase IIB project period, supported by investment funding secured during the SBIR project period. Impact: Project success would enable significant reductions in the use of high-risk catheters and circumvent the main barrier to increased self-care at home. This would greatly reduce the cost of kidney failure care and improve patient safety and quality of life for a significant part of the ESRD patient population. v0.34