Miniature MagLev VAD for Neonates and Pediatrics

描述（由申请人提供）：本研究计划的目标是将UltraMag心室辅助系统的开发从临床前阶段过渡到临床试验阶段，该系统旨在支持新生儿和幼儿。这项工作将在一项单中心、前瞻性、非随机、开放标签的临床试验中达到高潮。由NHLBI赞助的儿童心血管疾病研究工作组2001年的报告指出，迫切需要新的系统来支持患有严重心脏疾病的儿童。由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）开发的儿科心室辅助装置旨在满足婴儿和幼儿长达6个月的急性到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密封，轴承或其他传统上与血栓形成或机械故障相关的可移动部件。在项目的第一阶段，我们通过一系列的体外和体内实验证明了这项技术在儿科应用中的合理性。在二期项目中，我们优化了泵的设计，以适应儿科患者典型的血流动力学条件，并在一系列模拟典型临床条件的体内植入物中展示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领域的重要性和临床需求，我们在此提出一项II期持续拨款，以支持硬件开发完成其最终临床形式，使用临床级硬件进行一系列最终临床前动物验证研究，然后在FDA批准的研究器械豁免（IDE）下启动临床试验。我们的具体目标包括：目标1：在幼羊模型中展示设备耐久性和生物相容性，以确认临床试验准备就绪，提供长达180天的支持。将评估血泵、控制系统和导管的生理性能和生物相容性。目标2：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公斤的儿童）中进行为期180天的“初步临床安全性和可能获益”试验。该研究将包括一项单点试验，以评估生存率、血流动力学影响、可能的血栓形成、器械可靠性、终末器官功能障碍逆转以及断奶和恢复的可能性。最终目标是收集足够的数据，以说服FDA允许继续进行试验，以证明在通往HDE的过程中安全性和可能的益处。Levitronix打算在获得FDA批准之前，为首批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：开发UltraMag系统是为了满足对患有心肌病的儿童的支持需求，这些儿童由于心力衰竭而面临着持续的死亡威胁。小儿心室辅助装置旨在满足婴儿和幼儿临时心脏生命支持（长达180天）的需要。

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.