Development of SVAD System for HF Therapy

描述（由申请人提供）：本申请的目的是完成SCR SVAD系统的工程开发和临床前测试，为非晚期心力衰竭（HF）患者提供部分心脏辅助。心衰在世界范围内呈上升趋势，是卫生保健资源和费用的主要负担。尽管医疗保健有所进步，但心衰的预后仍然很差，特别是在晚期。目前，它需要大手术干预和体外循环（CPB），这与显著的不良事件发生率和较长的恢复时间有关。干预和患者随访的高成本限制了广泛接受。SVAD系统由一个小型轴流泵（铂合金叶轮和叶片扩散器）、流入左心房插管和流出腋动脉移植吻合组成。SVAD泵（长6厘米，直径2厘米，重40克）通过右侧小开胸植入。SVAD的临床益处包括：省去了大手术（胸骨切开术）、左室根尖取心和主动脉吻合；执行“关闭泵”（无CPB）；在锁骨下囊内放置泵，便于植入（和外植）手术；卓越的流体动力性能（5lpm @ 100mmhg），功耗要求低。在这个I-II期提案中，我们将论证SVAD的可行性，并完成工程开发和临床前测试，以支持FDA提交一期（n=10）和二期（n=300）临床试验。为了实现这一目标，我们将根据人体植入物质量体系的良好生产规范（GMP）规范完成SVAD系统的工程开发和设计冻结；通过完成验证和验证（V&V）测试（疲劳）、解剖匹配和手术程序研究（人体尸体，n=4）、体内急性（n=4）、慢性7天（n=6）和慢性45天（n=8）良好实验室规范（GLP）研究来证明疗效和生物相容性。临床前、V&V、GMP和GLP研究数据将用于支持IDE在心衰患者临床试验中的应用。我们的长期目标是

DESCRIPTION (provided by applicant): The objective of this proposal is to complete the engineering development and pre-clinical testing of the SCR SVAD system to provide partial cardiac assist in patients with less advanced stage heart failure (HF). HF is increasing worldwide and represents a major burden in terms of health care resources and costs. Despite advances in medical care, prognosis with HF remains poor, especially in advanced stages. Currently, it requires a major operative intervention and cardiopulmonary bypass (CPB), which have been associated with significant adverse event rates and long recovery. The high cost of the intervention and patient follow-up has limited widespread acceptance. The SVAD system consists of a miniaturized axial flow pump (platinum alloy impeller and vane diffuser), inflow cannulation to the left atrium, and outflow graft anastomosis to axillary artery. The SVAD pump (6 cm length, 2 cm diameter, 40 g weight) is implanted through a right lateral mini-thoracotomy. The clinical benefits of the SVAD include: eliminates major surgery (sternotomy), LV apical coring, and aortic anastomosis; performed 'off pump' (no CPB); pump placement in subclavicular pocket facilitates implant (and explant) procedure(s); and superior hydrodynamic performance (5 lpm @ 100 mmHg) with low power requirements. In this phase I-II proposal, we will demonstrate feasibility and complete engineering development and pre- clinical testing of the SVAD to support a FDA submission for phase one (n=10) and phase two (n=300) clinical trials. To achieve this objective, we will complete the engineering development and design freeze of the SVAD system with Good Manufacturing Practices (GMP) specifications for a human implant quality system; demonstrate efficacy and biocompatibility by completing Validation and Verification (V&V) testing (fatigue), anatomical fit and surgical procedure study (human cadaver, n=4), and in vivo acute (n=4), chronic 7-day (n=6), and chronic 45-day (n=8) Good Laboratory Practices (GLP) study. The pre-clinical, V&V, GMP, and GLP study data will be used to support an IDE application for a clinical trial in HF patients. Our long-term goal is to clinically translate the SCR SVAD to treat earlier stage HF patients, using miniaturized partial support device, and less invasive surgical tools and procedures to improve patient outcomes and restore quality of life.