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

• 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
• 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

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.

项目摘要/摘要 在美国，每年有多达14,000名儿童因心力衰竭(HF)相关疾病住院治疗 死亡率为7-15%。心脏移植是治疗的黄金标准，但心脏移植期间的死亡率 等待名单上有5%-39%；因此，使用机械循环支持(MCS)装置在 在这一具有挑战性和异质性的患者群体中支持心血管功能。MCS选项用于 新生儿和10公斤以下的婴儿特别有限，因为他们的身体习性使他们太小而无法接受 植入式技术。该项目的目标是完成灵感疗法的开发 NeoMate系统设计用于提供长达30天的MCS作为体外左心室辅助装置 (LVAD)适用于新生儿和婴儿心衰患者。NeoMate系统由一个紧凑的微型 离心式旋转泵、万能驱动器(带有嵌入式磁悬浮(磁悬浮)电机的控制器)、 以及外围组件(智能电池、触摸屏显示器)。在成功发展的基础上 在原型和可行性测试(在SBIR第一阶段完成)中，下两个设计迭代将是 在此SBIR第二阶段完成，包括用于预测流动的计算流体动力学(CFD)分析 动力学和溶血风险(目标1)，新Mate泵的开发(目标1)，以及 NeoMate集成控制器和电机及其外围设备(目标2)。NeoMate系统(第二和第三个设计) 迭代将在静态和动态模拟流环以及急性和慢性绵羊模型中进行测试，以评估 流体动力学、血流动力学和血液相容性性能(目标3)。数据将用于改进CFD 模型并反复改进NeoMate的工程设计、制造和性能 系统。NeoMate系统的潜在优势包括：(1)短期一次性低成本泵 MCS支持；(2)集成电机的可重复使用的磁悬浮通用控制器；(3)平台技术可以 支持未来多个临床心肺适应症的使用；(4)最小直径的叶轮(27 Mm)和 紧凑、集成和微型控制器(直径51 mm，高度115 mm，重量681g)。已完成的 SBIR第二阶段AIMS将使灵感治疗公司能够为IIB阶段研究做准备，以实现设计冻结 商业临床级NeoMate系统是否符合《良好制造规范》、 验证和验证测试，并按照GOOD实验室的要求完成临床前测试 练习。工程控制文件和实验数据将用于支持监管 提交申请以批准启动I期临床试验。灵感疗法的长期目标是 以这一平台技术为基础，最终将潜在市场扩展到体外循环领域， 呼吸辅助、体外膜氧合、双侧和右室辅助；然而，在 这项SBIR第二阶段应用，NeoMate系统正在开发和设计用于左心室 援助，首先是在服务不足的新生儿和婴儿心力衰竭人群中。