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: 10601060
• 负责人: WILLIAM J WEISS
• 金额: $ 74.35万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601060
• 关键词: 1 year old; 6 year old; Acquired von Willebrand disease; Adult; Animal Testing; Animals; Anticoagulation; Aorta; Attention; Berlin; Blood flow; Cannulas; Cannulations; Child; Childhood; Chronic; Circulation; Clinical; Clinical Protocols; Development; Device Designs; Devices; Diameter; 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; 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; Transplantation; Venous Pressure level; Ventricular; Waiting Lists; age group; biomaterial compatibility; clinic ready; clinical investigation; commercialization; cost; design; flexibility; hemodynamics; left ventricular assist device; manufacturing process development; mechanical circulatory support; 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.

摘要 需要机械循环支持以进行移植的婴幼儿的情况， 复苏仍然具有挑战性。一岁以下的儿童虽然人数最多，但选择很少 年龄组的儿童移植，并有最高的等待名单死亡率。虽然成人VAD是 有时用于较大的儿童，泵的尺寸和输出不匹配是显著的限制。柏林 心脏EXCOR VAD是唯一一种获批用于6岁以下患者的器械，但 血栓栓塞和神经功能障碍的发生率比成人VAD高10倍。的Jarvik 2015年小儿VAD处于早期临床试验中，但其在婴儿和右心中的使用存在局限性 支持.本提案的目的是完成宾夕法尼亚州立大学婴儿的临床前试验 心室辅助装置（VAD），这将是一个更安全的VAD左或右支持。婴儿VAD已被 在35项动物研究中作为左心室辅助装置（LVAD）进行了测试， 生物相容性。尽管有一个积极的协议，其中有很少或根本没有抗凝， 没有临床上明显的血栓栓塞或终末器官功能障碍。宾州州立大学婴儿VAD是一个 气动脉动装置虽然脉动式VAD在成人中已被连续流泵取代， 在婴儿中使用搏动方法是有优点的。这些包括血栓栓塞的低风险， 低抗凝水平下泵血栓形成，LVAD、RVAD或BiVAD插管灵活 支持、泵输出的自动预加载敏感控制、生理脉动、不存在净零或 在旋转泵中发生的低泵速下通过VAD的负血流量，以及 获得性血管性血友病综合征我们建议完成IDE提交所需的研究， FDA根据早期可行性研究计划。具体目标是： 目标1.完成VAD和插管的设计控制和制造过程开发， 包括RVAD的新入口套管。 目标2.完成便携式气动驱动器的设计，以支持早期可行性研究。 目标3.对LVAD、RVAD和BiVAD中的最终泵和驱动器进行体外验证测试 配置以证明血液动力学性能和可接受的溶血。 目标4。证明最终泵的安全性（可接受的低血栓栓塞和正常运行） 以及在高流量（3）和低流量范围（3）中LVAD和RVAD配置中的驱动器。 目标5。完成IDE前文件，设计EFS临床方案，召开预提交会议 并准备IDE提交。