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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的需要机械循环支持以桥接移植或的婴幼儿的情况一岁以下儿童的恢复仍然具有挑战性，尽管该年龄组的选择很少，但他们是最大的。尽管成人 VAD 的死亡率最高，但儿童移植的年龄组的等待名单死亡率最高。有时用于较大的儿童，柏林泵的尺寸和输出不匹配是很大的限制。 Heart EXCOR VAD 是唯一批准用于约 6 岁以下患者的设备，但是血栓栓塞和神经功能障碍的发生率比成人 VAD 高 10 倍。 2015 儿科 VAD 处于早期临床测试阶段，但其在婴儿和右心方面的使用存在局限性该提案的目标是完成宾夕法尼亚州立大学婴儿的临床前测试。心室辅助装置 (VAD) 将是一种更安全的 VAD，可用于婴儿 VAD 的左侧或右侧支撑。作为左心室辅助装置 (LVAD) 在 35 项动物研究中进行了测试，并表现出优异的性能尽管采取了积极的治疗方案，但几乎没有抗凝治疗。宾夕法尼亚州立大学婴儿 VAD 是尽管脉动 VAD 已被成人连续流泵取代，脉动方法对婴儿有好处，包括血栓栓塞风险低。抗凝水平较低的泵血栓，LVAD、RVAD 或 BiVAD 插管的灵活性支持、泵输出的自动预载敏感控制、生理脉动、净零或净零的缺失在低泵速下通过 VAD 的负血流发生在旋转泵中，并且没有我们建议完成向 IDE 提交所需的研究。 FDA 早期可行性研究计划的具体目标是：目标 1. 完成 VAD 和插管的设计控制和制造工艺开发，包括用于 RVAD 的新入口插管。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流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率和正常运行）以及高流量 (3) 和低流量 (3) 范围内 LVAD 和 RVAD 配置中的驱动器。目标 5. 完成预 IDE 文档，设计 EFS 临床方案，召开预分会议与 FDA 合作，并准备 IDE 提交。