Development of the Inspired Therapeutics NeoMate Mechanical Circulatory Support System for Neonates and Infants

项目总结/摘要 美国每年有多达14，000名儿童因心力衰竭（HF）相关疾病住院， 死亡率7- 15%。心脏移植是治疗的黄金标准，但在心脏移植期间的死亡率 等待名单是5-39%;因此，使用机械循环支持（MCS）设备发挥了重要作用， 支持这一具有挑战性和异质性的患者人群的心血管功能。MCS选项， 新生儿和10公斤以下的婴儿特别有限，因为他们的体型使他们太小，无法接受 植入式技术该项目的目标是完成Inspired Therapeutics的开发 NeoMate系统作为体外左心室辅助装置设计用于提供长达30天的MCS （LVAD）用于新生儿和婴儿HF患者。NeoMate系统由一个紧凑的微型 离心旋转泵，通用驱动器（带有嵌入式磁悬浮（MagLev）电机的控制器）， 和外围组件（智能电池、触摸屏显示器）。在成功发展的基础上， 原型和可行性测试（在SBIR第一阶段完成），接下来的两个设计迭代将是 在SBIR第二阶段完成，包括计算流体动力学（CFD）分析，以预测流量 动力学和溶血风险（目标1）、NeoMate泵的开发（目标1）以及 NeoMate集成控制器和电机及外围设备（Aim 2）。NeoMate系统（第2和第3种设计） 迭代将在静态和动态模拟流动回路以及急性和慢性绵羊模型中进行测试，以评估 流体动力学、血液动力学和血液相容性性能（目标3）。数据将用于完善CFD 模型，并迭代改进NeoMate的工程设计、制造和性能 系统NeoMate系统的潜在优势包括：（1）一次性低成本泵，用于短期 MCS支持;（2）可重复使用的MagLev通用控制器，带有集成电机;（3）平台技术可以 支持多种未来临床心肺适应症;（4）最小直径叶轮（27 mm）， 紧凑、集成和微型控制器（直径51 mm，高度115 mm，重量681 g）。完成 SBIR第二阶段的目标是使Inspired Therapeutics能够为IIB阶段研究做好准备，以实现设计冻结 商业临床级NeoMate系统符合良好生产规范， 验证和确认试验，并按照药物非临床研究质量管理规范完成临床前试验 实践工程控制文件和实验数据将用于支持监管 申请批准启动I期临床试验。Inspired Therapeutics的长期目标是 建立在该平台技术的基础上，最终将潜在市场扩展到心肺分流术， 呼吸辅助、体外膜氧合、双心室和右心室辅助;然而， 在SBIR第二阶段应用中，NeoMate系统正在开发和设计用于左心室 援助和服务不足的新生儿和婴儿HF人群第一。

Project Summary/Abstract Up to 14,000 children in the US are hospitalized with heart failure (HF)-related conditions each year with a mortality rate of 7-15%. Heart transplant is the gold standard of therapy, but the mortality rate while on the waiting list is 5-39%; thus, use of mechanical circulatory support (MCS) devices plays an important role in supporting cardiovascular function in this challenging and heterogenous patient population. MCS options for neonates and infants <10kg are especially limited, as their body habitus renders them too small to receive implantable technology. The objective of this project is to complete development of the Inspired Therapeutics NeoMate system designed to provide up to 30 days of MCS as an extracorporeal left ventricular assist device (LVAD) for neonate and infant HF patients. The NeoMate system is comprised of a compact, miniature centrifugal rotary pump, universal driver (controller with an embedded magnetically levitated (MagLev) motor), and peripheral components (smart battery, touch-screen monitor). Building upon the successful development of the prototype and feasibility testing (completed in SBIR phase I), the next two design iterations will be completed in this SBIR phase II, including computational fluid dynamics (CFD) analyses to predict flow dynamics and hemolysis risk (Aim 1), development of the NeoMate pump (Aim 1), and development of the NeoMate integrated controller and motor with peripherals (Aim 2). The NeoMate system (2nd and 3rd design) iterations will be tested in static and dynamic mock flow loops and acute and chronic ovine models to evaluate hydrodynamic, hemodynamic, and hemocompatibility performance (Aim 3). Data will be used to refine the CFD models and to iteratively improve the engineering design, fabrication, and performance of the NeoMate system. Potential advantages of the NeoMate system include: (1) disposable low-cost pumps for short-term MCS support; (2) reusable MagLev universal controller with integrated motor; (3) the platform technology may support multiple future clinical cardiopulmonary indications for use; (4) smallest diameter impeller (27mm) and compact, integrated, and miniature controller (51mm diameter, 115mm height, 681g weight). Completion of the SBIR Phase II aims will enable Inspired Therapeutics to prepare for a phase IIB study to achieve design freeze of the commercial clinical-grade NeoMate system in compliance with Good Manufacturing Practices, conduct verification and validation testing, and complete the pre-clinical testing in compliance with Good Laboratory Practices. Engineering control documents and experimental data will be used to support regulatory submissions for approval to initiate a phase I clinical trial. The long-term goal of Inspired Therapeutics is to build upon this platform technology to eventually expand the potential markets into cardiopulmonary bypass, respiratory assist, extracorporeal membrane oxygenation, and bi- and right ventricular assistance; however, in this SBIR phase II application, the NeoMate system is being developed and designed for left ventricular assistance and in the underserved neonate and infant HF populations first.