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

新生儿和婴儿 Inspired Therapeutics NeoMate 机械循环支持系统的开发

基本信息

批准号：
10547304
负责人：
Kurt A Dasse
金额：
$ 100.26万
依托单位：
INSPIRED THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10547304
关键词：
Acute Adult Animal Model Artificial Heart Benchmarking Body Size Caliber Cannulas Cardiopulmonary Cardiopulmonary Bypass Cardiovascular Physiology Cardiovascular system Child Childhood Chronic Clinical Clinical Data Computer software Data Development Devices Electronics Engineering Equilibrium Extracorporeal Membrane Oxygenation Family Feasibility Studies Freezing Future Goals Gold Heart Heart Transplantation Heart failure Height Hemolysis Housing Human Infant Island Left Liquid substance Magnetism Modeling Monitor Motor Oxygenators Patients Performance Peripheral Phase Phase I Clinical Trials Play Population Positioning Attribute Preclinical Testing Procedures Pump Quality of life Research Risk Role Safety Scheme Sheep Small Business Innovation Research Grant Speed Support System System Technology Testing Therapeutic Thrombus Training United States National Institutes of Health Universities Ventricular Vision Waiting Lists Weight commercialization cost data acquisition design engineering design feasibility testing good laboratory practice hemocompatibility hemodynamics implantable device improved left ventricular assist device mechanical circulatory support miniaturize mortality motor control neonate novel patient population pediatric heart failure pediatric patients phase 1 study phase 2 study portability pre-clinical prototype research and development respiratory assist response sheep model touchscreen ventricular assist device verification and validation

项目摘要

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.

项目概要/摘要美国每年有多达 14,000 名儿童因心力衰竭 (HF) 相关疾病住院治疗死亡率7-15%。心脏移植是治疗的金标准，但死亡率却很高等候名单为 5-39%；因此，机械循环支持（MCS）设备的使用在在这个具有挑战性和异质性的患者群体中支持心血管功能。 MCS 选项新生儿和<10公斤的婴儿尤其受到限制，因为他们的身体习惯使他们太小而无法接受植入技术。该项目的目标是完成 Inspired Therapeutics 的开发 NeoMate 系统旨在作为体外左心室辅助装置提供长达 30 天的 MCS (LVAD) 适用于新生儿和婴儿心力衰竭患者。 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）、以及外围组件（智能电池、触摸屏显示器）。在成功开发的基础上原型和可行性测试（在 SBIR 第一阶段完成），接下来的两次设计迭代将是在此 SBIR 第二阶段中完成，包括用于预测流量的计算流体动力学 (CFD) 分析动力学和溶血风险（目标 1）、NeoMate 泵的开发（目标 1）以及 NeoMate 集成控制器和电机以及外围设备（目标 2）。 NeoMate 系统（第二和第三设计）迭代将在静态和动态模拟流动循环以及急性和慢性绵羊模型中进行测试，以进行评估流体动力学、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）短期使用一次性低成本泵 MCS 支持； (2)可重复使用的MagLev通用控制器，带有集成电机； (3)平台技术可支持未来多种临床心肺适应症的使用； (4) 最小直径叶轮 (27mm) 和紧凑、集成、微型控制器（直径 51 毫米，高度 115 毫米，重量 681 克）。完成 SBIR II 期目标将使 Inspired Therapeutics 为 IIB 期研究做好准备，以实现设计冻结商业临床级 NeoMate 系统符合良好生产规范，进行验证和确认测试，并按照Good Laboratory完成临床前测试实践。工程控制文件和实验数据将用于支持监管提交批准启动 I 期临床试验的申请。 Inspired Therapeutics 的长期目标是以此平台技术为基础，最终将潜在市场扩展到心肺旁路，呼吸辅助、体外膜氧合以及双心室和右心室辅助；然而，在在本次 SBIR II 期应用中，NeoMate 系统正在针对左心室进行开发和设计首先是援助和服务不足的新生儿和婴儿心力衰竭人群。