Miniature MagLev VAD for Neonates and Pediatrics

描述（由申请人提供）：本研究计划的目的是将UltraMag心室辅助系统（旨在支持新生儿和幼儿）的开发从临床前阶段过渡到临床试验阶段。这项工作将最终在一个单一的中心，前瞻性，非随机，开放标签，临床试验。2001年由NHLBI赞助的儿科心血管疾病研究工作组的报告指出，迫切需要新的系统来支持患有严重心脏病的儿童。Levitronix及其开发合作伙伴德克萨斯心脏研究所（THI）和匹兹堡大学（UoP）正在开发的儿科心室辅助设备旨在满足婴儿和幼儿长达6个月的急性至慢性机械循环生命支持的需求。我们的目标是基于Levitronix开发的核心磁悬浮技术，为婴儿和幼儿创造一种可行的临床产品。独特的是，这种小型离心泵没有传统上与血栓形成或机械故障相关的密封件，轴承或其他可移动部件。在该项目的第一阶段，我们通过一系列体外和体内实验证明了该技术在儿科应用中的可靠性。在该项目的第II阶段，我们优化了泵设计，以适应儿科患者的典型血流动力学条件，并在一系列模拟典型临床条件的体内植入物中证明了有效的血流动力学性能和生物相容性。认识到将该技术快速推进到临床竞技场的重要性和临床需求，我们在此提议II期继续资助，以支持完成硬件开发至其最终临床形式，使用临床级硬件进行一系列最终临床前动物确认研究，然后根据FDA批准的试验用器械豁免（IDE）启动临床试验。我们的具体目标包括：目标1：在幼龄绵羊模型中证明器械的耐久性和生物相容性，以确认为临床试验做好准备，提供长达180天的支持。将评估血泵、控制系统和插管的生理性能和生物相容性。目标二：在8名患有失代偿性充血性心肌病的儿童（从新生儿到体重不超过40 kg的儿童）中进行长达180天的拟议系统的“初步临床安全性和可能受益”试验。该研究将包括一项单中心试验，以评估生存率、血流动力学效应、可能的血栓形成、器械可靠性、终末器官功能障碍的逆转以及脱机和恢复的可能性。最终目标是收集足够的数据，说服FDA允许继续进行试验，以证明HDE的安全性和可能的获益。Levitronix打算在获得FDA批准之前，为前8名患者以外的临床试验费用提供财政支持。公共卫生相关性：UltraMag系统正在开发中，以满足支持因心力衰竭而面临持续死亡威胁的心肌病儿童的需求。小儿心室辅助装置预期用于满足婴儿和幼儿的临时心脏生命支持（最长180天）需求。

DESCRIPTION (provided by applicant): The objective of this research plan is to transition the development of the UltraMag ventricular assist system, which is designed to support neonates and small children, from the preclinical to the clinical trial phase. The work will culminate in a single center, prospective, nonrandomized, open-label, clinical trial. The 2001 report of the NHLBI) sponsored Task Force on Research in Pediatric Cardiovascular Disease identified the pressing need for novel systems to support children with severely compromised cardiac disorders. The pediatric ventricular assist device under development by Levitronix and its development partners, the Texas Heart Institute (THI) and the University of Pittsburgh (UoP), is intended to fulfill the need for acute to chronic mechanical circulatory life support for up to 6-months in infants and small children. Our goal will be to create a viable clinical product for infants and small children, based on the core magnetically levitated technology developed by Levitronix. Uniquely, this small centrifugal pump has no seals, bearings, or other movable parts that are traditionally associated with thrombus formation or mechanical failure. In Phase I of the project, we demonstrated the soundness of this technology for the pediatric application through a series of in vitro and in vivo experiments. In Phase II of the project, we optimized the pump design to accommodate the hemodynamic conditions typical for the pediatric patient, and demonstrated effective hemodynamic performance and biocompatibility in a series of in vivo implants simulating typical clinical conditions. Acknowledging the importance and clinical need of advancing this technology rapidly into the clinical arena, we propose here a Phase II Continuation Grant to support the completion of the hardware development to its final clinical form, performance of a series of final pre-clinical animal validation studies using clinical- grade hardware, followed by initiation of the clinical trial under an FDA approved investigational device exemption (IDE). Our specific Aims include: Aim 1: Demonstrate device endurance and biocompatibility in a juvenile ovine model to confirm readiness for clinical trials providing support up to 180 days. Physiological performance and biocompatibility of the blood pump, control systems, and cannulae will be assessed. Aim 2: Conduct "preliminary clinical safety and probable benefit" trial for up to 180 days of the proposed system in 8 children (ranging from neonate to children weighing up to 40 kg) with decompensated congestive cardiomyopathy. The study will consist of a single-site trial to assess survival, hemodynamic effect, possible thrombogenesis, device reliability, reversal of end-organ dysfunction, and potential for weaning andrecovery. The ultimate goal is to gather sufficient data to convince FDA to allow continuation of the trial to prove safety and probable benefit en route to an HDE. Levitronix intends to financially support the clinical trial costs beyond the first eight patients until FDA approval is obtained. PUBLIC HEALTH RELEVANCE: The UltraMag system is being developed to address the need to support children with cardiomyopathies who face the constant threat of death due to heart failure. The pediatric ventricular assist device is intended to fulfill the need for temporary cardiac life support (up to 180-days) in infants and small children.