Final Pre-clinical Studies for a Ventricular Assist Device for Infants

婴儿心室辅助装置的最终临床前研究

• 批准号: 10165815
• 负责人: WILLIAM J WEISS
• 金额: $ 78.16万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10165815
• 关键词: 1 year old; 6 year old; Acquired von Willebrand disease; Adult; Animal Testing; Animals; Anticoagulation; Aorta; Attention; Berlin; Blood Circulation; Blood flow; Caliber; Cannulas; Cannulations; Child; Childhood; Chronic; Clinical; Clinical Protocols; Development; Device Designs; Devices; Documentation; Engineering; Extracorporeal Membrane Oxygenation; Feasibility Studies; Functional disorder; Future; Grant; Guidelines; Heart; Heart Transplantation; Hemolysis; In Vitro; Infant; Investments; Lead; Left; Left ventricular structure; Mechanics; National Heart, Lung, and Blood Institute; Neurologic Dysfunctions; Organ; Output; Patients; Performance; Physiological; Population; Positioning Attribute; Preclinical Testing; Protocols documentation; Pulmonary Circulation; Pump; Recovery; Risk; Safety; Speed; System; Technology; Testing; Thromboembolism; Thrombosis; Time; Transplantation; Venous Pressure level; Ventricular; Waiting Lists; age group; biomaterial compatibility; clinical investigation; commercialization; cost; design; flexibility; hemodynamics; left ventricular assist device; manufacturing process development; meetings; mortality; operation; portability; preclinical study; programs; prototype; research clinical testing; stroke risk; thrombogenesis; ventricular assist device

ABSTRACT The situation for infants and young children requiring mechanical circulatory support for bridge to transplant or recovery remains challenging. The under one year of age group has few options, although they are the largest age group for pediatric transplantation and have the highest waitlist mortality. Although adult VADs are sometimes used in larger children, the pump size and output mismatch are significant limitations. The Berlin Heart EXCOR VAD is the only device approved for patients under approximately 6 years of age, but thromboembolism and neurologic dysfunction occur at a rate 10 times higher than in adult VADs. The Jarvik 2015 Pediatric VAD is in early clinical testing but there are limitations to its use in infants and for right heart support. The objective of this proposal is to complete the pre-clinical testing of the Penn State Infant Ventricular Assist Device (VAD) which will be a safer VAD for left or right support. The Infant VAD has been tested as a Left Ventricular Assist Device (LVAD) in 35 animal studies, and has demonstrated excellent biocompatibility. Despite an aggressive protocol in which there has been little to no anticoagulation, there has been no clinically evident thromboembolism or end organ dysfunction. The Penn State Infant VAD is a pneumatic pulsatile device. Although pulsatile VADs have been replaced by continuous flow pumps in adults, there are advantages to the pulsatile approach in infants. These include a low risk of thromboembolism and pump thrombosis with low levels of anticoagulation, flexibility in cannulation for LVAD, RVAD or BiVAD support, automatic preload–sensitive control of pump output, physiologic pulsatility, the absence of net zero or negative blood flow through the VAD at low pump speed which occurs in rotary pumps, and absence of acquired von Willebrand syndrome. We propose to complete the studies required for an IDE submission to the FDA under the Early Feasibility Study program. The specific aims are: Aim 1. Complete design controls and manufacturing process development for the VAD and cannulae, including a new inlet cannula for the RVAD. Aim 2. Complete the design of the portable pneumatic Driver to support an Early Feasibility Study. Aim 3. Perform in vitro verification testing of the final pump and driver in the LVAD, RVAD, and BiVAD configurations to demonstrate hemodynamic performance and acceptable hemolysis. Aim 4. Demonstrate safety (acceptably low thromboembolism and normal operation) of the final pump and driver in the LVAD and RVAD configurations in the high flow (3) and low flow ranges (3). Aim 5. Complete the pre-IDE documentation, design the EFS clinical protocol, hold a pre-sub meeting with FDA, and prepare an IDE submission.

抽象的 婴儿和幼儿的情况需要机械电路支持移植或 恢复仍然受到挑战。一个年龄段以下的年龄段的选择很少，尽管它们是最大的选择 小儿移植的年龄组，并且具有最高的等待名单死亡率。虽然成人vad是 有时在较大的儿童中使用，泵的大小和输出不匹配是显着的局限性。柏林 Heart Excor VAD是唯一批准了大约6岁以下患者的设备，但 血栓栓塞和神经功能障碍的发生率是成年vad的10倍。贾维克 2015年小儿VAD正在早期临床测试中 支持。该提案的目的是完成宾夕法尼亚州婴儿的临床前测试 心室辅助装置（VAD）将是左或右支撑的安全VAD。婴儿vad一直是 在35个动物研究中作为左心室辅助装置（LVAD）进行了测试，并且表现出极好的 生物相容性。尽管有一些积极的方案，几乎没有抗凝治疗，但 我们没有临床证明的血栓栓塞或最终器官功能障碍。宾夕法尼亚州立婴儿VAD是 尽管脉动vads已被成年人的连续流动泵所取代，但 婴儿的脉动方法具有优势。这些包括血栓症的低风险和 抗凝水平较低的泵血栓形成，LVAD，RVAD或BIVAD的插管灵活性 支持，自动预加载泵输出的敏感控制，生理脉冲性，缺乏净零或 负血流在旋转泵中发生的低泵速度流过VAD，没有 获得的冯·威勒布兰综合症。我们建议完成提交IDE提交所需的研究 FDA在早期可行性研究计划下。具体目的是： AIM 1。vad和innulae的完整设计控制和制造过程开发， 包括新的RVAD入口套管。 目标2。完成便携式气动驱动器的设计，以支持早期的可行性研究。 AIM 3。在LVAD，RVAD和BIVAD中对最终泵和驱动器进行体外验证测试 构型表明血液动力学性能和可接受的溶血。 目标4。最终泵的安全性（可接受的血栓栓塞和正常操作） 高流量（3）和低流量范围（3）中的LVAD和RVAD配置中的驱动器。 目标5。完成id易之前的文档，设计EFS临床协议，举行预召开会议 使用FDA，准备IDE提交。