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

描述(申请人提供)：心力衰竭和先天性心脏缺陷每年威胁数千名儿童的生命。唯一获得FDA批准的长期儿科心脏支持设备是柏林心脏激励器，它基于已有30多年历史的技术，充满了并发症，包括需要频繁更换设备的设备中形成的血栓。这项技术的接受者中风、出血和感染的风险很高，而且泵是由一个220磅的大泵驱动的。操纵台，这限制了病人的行动和防止医院出院。尽管有这些严重的限制，90%的Excor接受者可以存活到移植，尽管支持的中位数只有35天。一种更安全的设备将极大地减少支持的并发症，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，即革命，其中可以对两个组件进行微小修改，以调整泵的性能，以支持心脏的右侧或左侧。这些设备的直径为8毫米，长度为50毫米，大约相当于一个AAA电池的大小，而市场领先的HeartMate II的最大直径为47毫米，长度为95毫米，相当于一个D电池的大小。我们的成人革命RVAD可以安全地产生儿科左心辅助装置所需的较低的血率，并且在台式研究中和在绵羊植入期间显示出极低的血液创伤，最长可达一个月，无需长期使用血液稀释剂。在这些有希望的结果的基础上，我们提出了一种快速通道，结合第一阶段/第二阶段SBIR，将InnovRVAD重新用于1岁及以上儿童的儿科左心辅助装置-Revation mini。然后，我们将修改设计，为0-1岁的新生儿和婴儿创建革命NEO，他们代表着儿科心脏支持的最大临床需求。在第一阶段中，我们将展示Mini在体外和短期动物实验中对儿科血流速度和压力的可行性和有效性。在第二阶段，我们将进行长期动物植入，以评估泵的长期功能、生物兼容性和耐用性，并对革命微型系统进行验证和验证研究，为美国的临床试验做准备。在整个项目中，我们将把相当大的精力集中在解剖匹配建模上 并研究设计方法，以便将这些设备植入儿童较小的身体，以避免泵从身体伸出，就像ParacorporealExcor所发生的那样。卓越的血液兼容性、更小的尺寸和利用成人系统组件的能力相结合，可以生产出并发症更少、允许患者出院回家的儿科心脏辅助设备，并且在经济上是可行的，可以彻底改变儿科心力衰竭的治疗。

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.