Development of an intravascular circulatory support device for high-risk for percutaneous coronary intervention and cardiogenic shock

经皮冠状动脉介入治疗和心源性休克高危人群血管内循环支持装置的研制

• 批准号: 10006621
• 负责人: Jeffrey LaRose
• 金额: $ 49.16万
• 依托单位: RT CARDIAC SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006621
• 关键词: Acute; Address; Adult; Adverse event; Anatomy; Animal Model; Aortic Valve Insufficiency; Benchmarking; Blood; Blood Preservation; Blood flow; Cardiac; Cardiogenic Shock; Catheters; Cattle; Characteristics; Chronic; Clinical; Clinical Trials; Convection; Convulsive therapy; Data; Data Analyses; Development; Devices; Diagnostic; Diffuse; Electromagnetics; Engineering; Ensure; Erythrocytes; Extracorporeal Membrane Oxygenation; FDA approved; Failure; Family; Freezing; Goals; Head; Healthcare; Heart; Heart failure; Hemolysis; Heparin; Housing; Image; Implant; In Vitro; Incidence; Intra-Aortic Balloon Pumping; Intraventricular; Ischemia; Left; Left ventricular structure; Legal patent; Liquid substance; Lower Extremity; Lubrication; Measures; Mechanics; Medical; Medical Device; Modeling; Motor; Normalcy; Operative Surgical Procedures; Organ; Outcome; Patients; Performance; Perfusion; Pharmaceutical Preparations; Phase; Physiological; Positioning Attribute; Preclinical Testing; Pump; Radial; Reporting; Research; Resistance; Resources; Rotation; Sampling; Serious Adverse Event; Speed; Support System; Surface; System; Technology; Testing; Therapeutic; Thrombosis; Time; Torque; Translating; Trauma; Treatment Failure; Vision; Visualization; Work; base; blood pump; clinical practice; clinically relevant; cost; data exchange; design; experience; flexibility; good laboratory practice; hemodynamics; high risk; implantation; improved; in vivo; indexing; innovation; innovative technologies; left ventricular assist device; meetings; miniaturize; novel; operation; outcome forecast; patient population; pediatric patients; percutaneous coronary intervention; phase 1 study; phase 2 study; platelet preservation; pressure; purge; renal damage; risk minimization; simulation; technological innovation; verification and validation

The objective of this proposal is to continue engineering development and pre-clinical testing of a novel percutaneous mechanical circulatory support (pMCS) device for use during high risk percutaneous coronary intervention (PCI) and cardiogenic shock (CS). The high-incidence of PCI and CS are significant and increasing worldwide, representing a major burden in terms of health care resources and costs. Current treatment options, including medications and other medical devices, are limited by ineffectiveness, insufficient support, adverse events, and/or require major surgical intervention. To address this need, RT Cardiac Systems (RTCS, Cary NC) has developed novel blood pump technology enabling greater hemodynamic support than previously possible. Other companies report high “peak flows” at sub-therapeutic aortic pressures indicative of poor patient prognosis and/or severe aortic insufficiency. The RTCS device provides mean flow over 4 L/min against mean aortic pressure of 80 mmHg, which is sufficient to restore end organ perfusion. Other known devices can only produce mean flows of 3 L/min or less at this therapeutic condition. With extensive blood pump design gained developing the HeartWare HVAD, MVAD, and intraventricular MVAD family of chronic LVAD’s, RTCS has achieved this high level of support with low levels of blood trauma. Subsequently, RTCS has the expertise, experience, and confidence that we will achieve our objective of commercializing a competitive pMCS device to improve therapy for high-risk PCI and CS patient populations. The proprietary RT Cardiac System pMCS device (US patent application 15/676,281) consists of a miniaturized axial flow pump (2-bladed impeller, 3-bladed diffuser) and an intravascular motor (slotted, brushless DC motor) connected via a short flexible drive system. The device flexibility improves implantation and resistance to occlusion as the device adapts to the native left ventricle anatomy. The short drive system design, including bearing material selections, does not require an external purge of lubrication system that is required of all other known devices. The high hydraulic efficiency of the pMCS device reduces blood trauma, required motor torque, and rotational speed to achieve design flow rates. The high motor efficiency reduces the power required and heat dissipation load. Rigor of prior research with proof-of-concept testing was demonstrated as evidenced by completion of flow visualization (capacity, washing, blood preservation) and in vitro (hydraulic and electro-mechanical performance) analyses. In this phase I project, we will (1) complete fabrication of the pMCS motor system (Aim 1); (2) demonstrate engineering performance in static (HQ curves) and dynamic (hemodynamics) mock loop model (Aim 1), (3) demonstrate system reliability in 30-day system reliability testing (Aim 1), (4) demonstrate physiologic efficacy (hemodynamics, blood, imaging) in a large animal model (Aim 2), and (5) evaluate surgical placement in a large animal model (Aim 2). Successful demonstration of feasibility of the RTCS pMCS system will include: (1) novel drive system reliability, (2) achieve engineering performance benchmarks, (3) physiologic efficacy (pump flow, minimal hemolysis), and (4) device in vivo delivery and positioning. Collectively, upon successful demonstration of meeting design benchmarks and study metrics (phase I), we will work to achieve a design freeze, complete verification and validation testing in compliance with Good Manufacturing Practices (GMP), and pre-clinical testing in compliance with Good Laboratory Practices (GLP) with all of our engineering control documents and pre-clinical test data and analyses used to support a IDE application for a clinical trial in PCI and CS patients. Our vision is to successfully translate the pMCS system and a family of catheter-based products into clinical practice for high-risk PCI and CS in adults as well right heart and biventricular failure therapies in adult and pediatric patients.

该提案的目的是继续对新型药物进行工程开发和临床前测试 用于高危经皮冠状动脉手术的经皮机械循环支持 (pMCS) 装置 干预（PCI）和心源性休克（CS）。 PCI 和 CS 的高发生率是显着的 在世界范围内不断增加，对医疗保健资源和成本构成了重大负担。当前的 治疗选择，包括药物和其他医疗设备，因无效、不足而受到限制 支持、不良事件和/或需要重大手术干预。为了满足这一需求，RT Cardiac Systems（RTCS、Cary NC）开发了新型血泵技术，可实现更大的血流动力学 支持比以前可能的。其他公司报告亚治疗主动脉的高“峰值流量” 表明患者预后不良和/或严重主动脉瓣关闭不全的压力。 RTCS 设备提供 平均流量超过 4 L/min，平均主动脉压为 80 mmHg，足以恢复终末器官 灌注。其他已知的装置在此治疗条件下只能产生 3 L/min 或更低的平均流量。 凭借广泛的血泵设计，开发了 HeartWare HVAD、MVAD 和心室内 RTCS 是慢性 LVAD 的 MVAD 家族，以低水平的血液创伤实现了这种高水平的支持。 随后，RTCS 拥有专业知识、经验和信心，我们将实现我们的目标： 将具有竞争力的 pMCS 设备商业化，以改善高风险 PCI 和 CS 患者群体的治疗。 专有的 RT 心脏系统 pMCS 设备（美国专利申请 15/676,281）由 小型轴流泵（2 叶片叶轮、3 叶片扩散器）和血管内电机（开槽、 无刷直流电机）通过短的柔性驱动系统连接。装置的灵活性改善了植入 由于该装置适应了原生左心室解剖结构，因此具有抗阻塞性。短驱动系统 设计，包括轴承材料的选择，不需要润滑系统的外部吹扫 所有其他已知设备都需要。 pMCS装置的高液压效率减少了血液创伤， 达到设计流量所需的电机扭矩和转速。高电机效率降低了 所需功率和散热负载。先前研究和概念验证测试的严谨性是 通过完成流动可视化（容量、清洗、血液保存）和在 体外（液压和机电性能）分析。 在这个第一阶段项目中，我们将（1）完成pMCS电机系统的制造（目标1）； (2) 演示 静态（HQ 曲线）和动态（血流动力学）模拟环路模型的工程性能（目标 1）、（3） 在 30 天的系统可靠性测试中证明系统可靠性（目标 1），(4) 证明生理功效 （血流动力学、血液、成像）在大型动物模型中（目标 2），以及 (5) 评估手术位置 大型动物模型（目标 2）。 RTCS pMCS 系统可行性的成功论证将包括：(1) 新颖的驱动系统可靠性，(2) 达到工程性能基准，(3) 生理功效（泵 (4) 装置体内输送和定位。成功后集体 演示满足设计基准和研究指标（第一阶段），我们将努力实现设计 冷冻，按照良好生产规范 (GMP) 完成验证和验证测试， 和临床前测试符合良好实验室规范 (GLP) 以及我们所有的工程控制 用于支持 PCI 临床试验 IDE 应用程序的文档、临床前测试数据和分析 和 CS 患者。我们的愿景是成功转化 pMCS 系统和一系列基于导管的系统 产品进入成人高风险 PCI 和 CS 以及右心和双心室衰竭的临床实践 成人和儿童患者的治疗。