Regulatory Support Administrative Supplement for Development of a Pediatric Ventricular Assist Device

描述（由申请人提供）：心力衰竭和先天性心脏缺陷每年威胁着数千名儿童的生命。fda唯一批准的长期儿童心脏支持装置是柏林心脏Excor，它基于30多年前的技术，充满并发症，包括设备内形成血栓，需要经常更换设备。这项技术的接受者中风、出血和感染的风险很高，泵由一个220磅的大控制台驱动，这限制了患者的行动能力，并防止出院。尽管存在这些严重的限制，90%的exor受者存活到移植，尽管支持的中位持续时间仅为35天。一个更安全的设备将大大减少支持的并发症，允许出院回家，并允许医生在孩子到达死亡边缘之前更早地部署这项技术。VADovations正在开发一种微型植入式泵平台Revolution，该平台可以对两个组件进行微小修改，以调整泵的性能，以支持右侧或左侧心脏。该产品的直径为8毫米，长度为50毫米，相当于AAA级电池的大小。相比之下，目前市场上领先的心脏伴侣II型电池的最大直径为47毫米，长度为95毫米，相当于D级电池的大小。我们的成人Revolution RVAD可以安全地产生儿童左心辅助装置所需的较低的血液速率，并且在实验台上研究和在没有长期血液稀释剂的情况下在绵羊中植入长达一个月的时间内证明了非常低的血液创伤。基于这些有希望的结果，我们提出了一个快速通道，联合I/II期SBIR，将Revolution RVAD重新定位为1岁及以上儿童的儿童左心辅助装置，即Revolution MINI。然后，我们将修改设计，为0-1岁的新生儿和婴儿创造革命NEO，他们代表了儿科心脏支持的最大临床需求。在第一阶段，我们将在体外和短期动物实验中证明MINI对儿童血流速率和压力的可行性和有效性。在II期，我们将进行慢性动物植入，以评估泵的长期功能、生物相容性和耐久性，并对Revolution MINI系统进行验证和验证研究，为美国临床试验做准备。在整个项目中，我们将重点关注解剖学拟合模型

DESCRIPTION (provided by applicant): Heart failure and congenital heart defects threaten the lives of several thousand children each year. The only FDA-approved long term pediatric heart support device is the Berlin Heart Excor, which is based on 30+ year old technology and is fraught with complications including blood clots forming in the device requiring frequent device replacement. The recipients of this technology are at high risk for strokes, bleeding, and infection and the pumps are driven by a large 220 lb. console, which limits patient mobility and prevents hospital discharge. In spite of these severe limitations, 90% of Excor recipients survive to transplant, although the median duration of support is only 35 days. A safer device would dramatically reduce the complications of support, permit discharge to home, and allow doctors to deploy the technology earlier, before a child reaches the brink of death. VADovations is developing a miniature implantable pump platform, the Revolution, in which minor modifications of 2 components can be implemented to adjust the pump performance to support the right or left side of the heart. The devices are 8 mm in diameter and 50 mm in length, about the size of a 'AAA' battery, compared to the market leading Heartmate II, which is 47 mm in maximum diameter and 95 mm in length, the size of a 'D' cell battery. Our adult Revolution RVAD can safely generate the lower blood rates needed for a pediatric left heart assist device and has demonstrated exceptionally low blood trauma in bench-top studies and during implants in sheep for durations up to one month with no long-term blood thinners. Building upon these promising results, we propose a Fast Track, combined Phase I/II SBIR to re-purpose the Revolution RVAD as a pediatric left heart assist device, the Revolution MINI, for children ages 1 and up. Then we will revise the design to create the Revolution NEO for neonates and infants, aged 0-1, who represent the largest clinical need for pediatric heart support. During Phase I, we will demonstrate the feasibility and efficacy of the MINI for pediatric blood flow rates and pressures during in vitro and short term animal experiments. In Phase II, we will conduct chronic animal implants to evaluate the long-term function, biocompatibility, and durability of the pumps and perform verification and validation studies of the Revolution MINI system to prepare for a US clinical trial. Throughout the program, we will focus considerable efforts on anatomic fit modeling and studies to devise approaches so that these devices can be implanted in the smaller bodies of children, to avoid pumps protruding from the body, as occurs with the paracorporeal Excor. Superior hemocompatibility, smaller size, and the ability to leverage adult system components, combine to produce pediatric heart assist devices that will offer fewer complications, permit patient discharge to home, and be economically viable to revolutionize the treatment of pediatric heart failure.