Apical Access System with Universal Connector for Beating Heart LVAD Implantation

带有用于跳动心脏 LVAD 植入的通用连接器的心尖接入系统

• 批准号: 8627238
• 负责人: Jorge Hernan Jimenez
• 金额: $ 101.45万
• 依托单位: APK ADVANCED MEDICAL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8627238
• 关键词: Acute; Adoption; Adverse event; Air; Animal Experiments; Animal Testing; Animals; Apical; Biomedical Engineering; Blood; Blood donor; Cadaver; Cannulas; Cardiopulmonary Bypass; Cardiovascular system; Caring; Cattle; Cells; China; Chronic; Clinical; Clinical Engineering; Clinical Trials; Computer Simulation; Coupling; Development; Devices; Disease; Engineering; Exposure to; Extravasation; Fatigue; Finite Element Analysis; Freezing; Future; Geometry; Goals; Government Agencies; Health; Healthcare; Healthcare Systems; Heart; Heart Transplantation; Heart failure; Hemorrhage; Hemostatic Agents; Hospitals; Human; Implant; India; Institutes; Intervention; Lead; Left; Left ventricular structure; Legal patent; Marketing; Measurable; Medical; Medical Technology; Metric; Modeling; Morbidity - disease rate; Myocardium; Operative Surgical Procedures; Outcome; Patients; Phase; Postoperative Period; Procedures; Quality of life; Recovery; Research Personnel; Resources; Retrieval; Risk; Role; Safety; Secure; Small Business Innovation Research Grant; Spatial Distribution; Staging; Sterilization; Study models; Surgical incisions; Surgical sutures; Suture Techniques; System; Techniques; Technology; Testing; Time; Translating; Treatment Cost; Underserved Population; Validation; biomaterial compatibility; clinical practice; commercialization; cost; design; follow-up; good laboratory practice; implantation; improved; in vivo; innovation; meetings; miniaturize; minimally invasive; mortality; outcome forecast; pre-clinical; prevent; product development; prototype; seal; tool; ventricular assist device; verification and validation

DESCRIPTION (provided by applicant): The objective of this proposal is to complete development of a long-term, universal Apical Access System (AAS) to improve clinical outcomes and expand the role of left ventricular assist device (LVAD) therapy. The treatment of end stage heart failure (HF) is the greatest challenge, both clinically and economically to the U.S. health care system today. With >800,000 people suffering with end stage HF and only 2,300 heart transplants and 4,600 LVADs implanted annually there is large a population underserved. LVAD implantation requires a major operative procedure with significant peri- and post-operative bleeding complications, mortality, and treatment costs. APK Advanced Medical Technologies, Inc. AAS System will allow current LVADs and future "Mini-VADs" to be implanted suture-less through a minimally invasive incision without placing the patient on cardiopulmonary bypass (CPB). By eliminating CPB, reducing access time and reducing bleeding, a significant and measurable impact on patient health and procedural cost will be achieved. The different components of the AAS System have been tested previously on the bench, in FEA computational models, and through acute and chronic (up to 12 weeks) animal experiments with positive results. The specific aims of the current proposal are: Phase I-Aim 1: Complete fabrication of the integrated components for the re-designed AAS System and demonstrate feasibility for LVAD therapy in acute bovine model (n=2) and human cadaver (n=2). Phase II-Aim 1: Complete the engineering development and design freeze of the LVAD AAS in compliance with Good Manufacturing Practices (GMP) specifications for a human implant quality system. Aim 2: Demonstrate safety and efficacy of the AAS System by completing risk analysis driven validation and verification testing. Testing to include: 600 Millio cycle fatigue, leakage/burst testing in pressurized hearts, Finite element analysis of anchoring components, sterilization validation and biocompatibility, anatomical fit and surgical procedure study (human cadaver, n=8), and in vivo acute (n=6), 14-day (n=6), and 30-day (n=6) in a chronic bovine model with HM II (Thoratec) and HVAD (HeartWare) devices. Successful outcomes will be quantified by metrics to include; incision size, ease of use, implantation time, blood loss, durability (fatigue on clinical-grade components), need for CPB, conformance to biocompatibility and sterilization ISO standards, and secure connection without air entrainment or leakage. Aim 3: Demonstrate long-term safety and reliability of the LVAD AAS in 30-day pre-GLP (n=2) and GLP (n=4) chronic bovine model study to support an IDE application for a clinical trial in patients with advanced heart failure receiving LVAD implantation only. The successful execution of this SBIR project will lead to development of a new clinical paradigm in the treatment of HF. Specifically the AAS will reduce surgical complexity and make LVAD therapy affordable leading to improved patient outcomes and quality of life. Ultimately, clinical acceptance to treat earlier stage HF patients and expansion into global markets can be achieved.

描述（由申请人提供）：本提案的目的是完成长期、通用心尖通路系统（AAS）的开发，以改善临床结果并扩大左心室辅助装置（LVAD）治疗的作用。终末期心力衰竭（HF）的治疗是当今美国医疗保健系统在临床和经济上面临的最大挑战。超过 800,000 人患有终末期心力衰竭，每年仅进行 2,300 例心脏移植手术和 4,600 例 LVAD 植入，有大量人口得不到充分的服务。 LVAD 植入需要一个重大的手术过程，具有显着的围手术期和术后出血并发症、死亡率和治疗费用。 APK Advanced Medical Technologies, Inc. AAS 系统将允许当前的 LVAD 和未来的“Mini-VAD”通过微创切口进行无缝合植入，无需对患者进行体外循环 (CPB)。通过消除体外循环、减少就诊时间和减少出血，将对患者健康和手术成本产生重大且可衡量的影响。 AAS 系统的不同组件之前已在 FEA 计算模型中进行了测试，并通过急性和慢性（长达 12 周）动物实验进行了测试，并取得了积极的结果。当前提案的具体目标是： 第一阶段目标 1：完成重新设计的 AAS 系统的集成组件的制造，并证明在急性牛模型 (n=2) 和人类尸体 (n=2) 中进行 LVAD 治疗的可行性）。第二阶段目标 1：按照人体植入物质量体系的良好生产规范 (GMP) 规范，完成 LVAD AAS 的工程开发和设计冻结。目标 2：通过完成风险分析驱动的验证和验证测试来证明 AAS 系统的安全性和有效性。测试包括：600 Millio 循环疲劳、加压心脏泄漏/爆裂测试、锚固部件的有限元分析、灭菌验证和生物相容性、解剖学配合和手术程序研究（人体尸体，n=8）以及体内急性（n =6)、14 天 (n=6) 和 30 天 (n=6)，在使用 HM II (Thoratec) 和 HVAD (HeartWare) 的慢性牛模型中设备。成功的结果将通过指标进行量化，包括：切口尺寸、易用性、植入时间、失血量、耐用性（临床级组件的疲劳）、CPB 需求、符合生物相容性和灭菌 ISO 标准，以及安全连接，无空气夹带或泄漏。目标 3：在 30 天 GLP 前 (n=2) 和 GLP (n=4) 慢性牛模型研究中证明 LVAD AAS 的长期安全性和可靠性，以支持 IDE 在晚期患者临床试验中的应用仅接受 LVAD 植入的心力衰竭。该 SBIR 项目的成功执行将导致心力衰竭治疗新临床范例的开发。具体来说，AAS 将降低手术复杂性，并使 LVAD 治疗变得经济实惠，从而改善患者的治疗效果和生活质量。最终，可以实现治疗早期心力衰竭患者的临床接受并扩展到全球市场。