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进行工程开发和临床前测试 经皮机械电路支撑（PMCS）设备，用于高风险经皮冠状动脉 干预（PCI）和心源性休克（CS）。 PCI和CS的高含量很重要，并且 在全球范围内增加，代表了医疗资源和成本方面的重大燃烧。当前的 治疗选择，包括药物和其他医疗设备，受到无效性的限制，不足 支持，不良事件和/或需要进行重大的手术干预。为了满足这种需求，RT心脏 系统（RTCS，Cary NC）开发了新型的血泵技术，使血液动力学更大 支持以前可能。其他公司报告了亚治疗性主动脉的高“峰值流” 压力表明患者提示不良和/或严重主动脉症不足。 RTCS设备提供 平均流量超过4 l/min，平均主动脉压力为80 mmHg，这足以恢复末端器官 灌注。在这种治疗条件下，其他已知设备只能产生3 l/min或更少的平均流量。 随着广泛的血液泵设计的发展，开发了Heantware HVAD，MVAD和室内室内 RTC的慢性LVAD的MVAD家族已经获得了低水平的血液创伤的高水平支持。 随后，RTCS具有专业知识，经验和信心，我们将实现我们的目标 将竞争性PMC设备商业化，以改善高危PCI和CS患者人群的治疗。 专有RT心脏系统PMCS设备（美国专利申请15/676,281）由一个组成 微型轴向流动泵（2叶片叶轮，3叶片扩散器）和血管内运动（槽， 无刷直流电动机）通过短柔性驱动系统连接。设备的灵活性改善了植入 并且随着设备适应天然左心室解剖结构的耐药性。短驱动系统 设计，包括轴承材料的选择，不需要外部清除润滑系统 所有其他已知设备的要求。 PMCS设备的高水解效率降低了血液创伤， 所需的电动机扭矩和旋转速度以实现设计流量。高运动效率降低 所需的功率和散热载荷。对概念证明测试的先前研究严格是 通过完成流动可视化（容量，洗涤，保存血液）和IN的完成证明了 体外（液压和电力性能）分析。 在此I阶段项目中，我们将（1）完整制造PMCS电机系统（AIM 1）； （2）演示 静态（HQ曲线）和动态（血液动力学）模拟循环模型（AIM 1），（3）中的工程性能 在30天的系统可靠性测试中展示系统可靠性（AIM 1），（4）证明生理效率 （血液动力学，血液，成像）在大型动物模型中（AIM 2），（5）评估手术放置 大动物模型（AIM 2）。成功证明RTCS PMCS系统的可行性将包括：（1） 新颖的驱动系统可靠性，（2）成就工程性能基准，（3）生理效率（泵 流量，最小溶血）和（4）体内递送和定位的装置。共同，成功 开会设计基准和研究指标（第一阶段）的演示，我们将努力实现设计 根据良好的制造实践（GMP）冻结，完整的验证和验证测试， 并符合我们所有的工程控制 用于支持PCI临床试验的IDE应用的文档和临床前测试数据和分析 和CS患者。我们的愿景是成功翻译PMCS系统和基于导管的家族 成人高风险PCI和CS的临床实践，以及正确的心脏和双室衰竭 成人和小儿患者的疗法。