Pre-clinical Testing of a VAD for Uni- and Bi-ventricular Support in Infants

VAD 对婴儿单心室和双心室支持的临床前测试

• 批准号: 8681498
• 负责人: WILLIAM J WEISS
• 金额: $ 71.19万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-02 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681498
• 关键词: Adult; Anatomy; Animal Testing; Animals; Anticoagulation; Benefits and Risks; Berlin; Biomedical Engineering; Blood Platelets; Cannulas; Cannulations; Cardiopulmonary; Childhood; Chronic; Clinical; Clinical Trials; Coagulation Process; Custom; Data; Destinations; Development; Device Designs; Device or Instrument Development; Devices; Engineering; Exhibits; Heart; Heart Diseases; Heart Transplantation; Hematology; Hemorrhage; Heparin; In Vitro; Incidence; Infant; Investments; Left; Liquid substance; Maps; Measures; Mechanics; Methods; Modeling; NIH Grants and Contracts; Nature; Operative Surgical Procedures; Output; Pathology; Patients; Pediatrics; Polymers; Protocols documentation; Pump; Recovery; Renal function; Research; Research Project Grants; Risk; Simulate; Staging; Stroke Volume; Support Contracts; System; Technology; Testing; Thromboembolism; Thrombosis; Thrombus; Time; Transplantation; United States National Institutes of Health; Ventricular; Veterinary Medicine; Weaning; Work; base; design; flexibility; heart function; in vivo; innovation; multidisciplinary; operation; patient population; pre-clinical; research clinical testing; ventricular assist device

DESCRIPTION (provided by applicant): The long term objective of this research is to provide a Ventricular Assist Device (VAD) designed specifically for infants, who require mechanical circulatory support of left, right, or both ventricles. The use of VADs in adults has become a viable means of support in end stage heart disease, as a bridge-to-transplant, and more recently as destination therapy. However, the only devices currently available for infants are either limited in support duration (typically 1 month) or carry significant thromboembolic and bleeding risks. The specific objective of this project is to perform pre-clinical testing of the Pen State Infant VAD. The Penn State Infant VAD is a pulsatile pneumatically-actuated pump with a 12-14 ml stroke volume. The device has demonstrated low thrombogenicity in pilot animal studies, in part due to the custom Bjork-Shiley monostrut valves, as used in the Thoratec adult VAD. The monostrut valve does not exhibit the recirculation regions found behind the leaflets in polymer trileaflet valves. We have also developed an innovative approach to cannulae design, which has been a shortcoming in current pediatric VADs, and which is critical to reducing thromboembolic risk, especially in infants and in those with congenital anatomic variability. The primary objective of this project is to perform pre-clinical testing (in vivo and in vitro) of the enn State Infant VAD and new cannulae system, leading to a clinical trial. A secondary objective is to investigate the mechanisms of thrombus formation, thromboembolism in a VAD system, by testing of the Infant VAD over a wider range of pump flow and anticoagulation states than would normally be required for regulatory approval, using multiple measures of coagulation, platelet function, renal function, and explant analyses. This objective represents an opportunity to contribute to the broader field of circulatory support device development and the design of animal testing protocols, especially in regards to anticoagulation approaches. The specific aims are: 1) to perform pre-clinical testing in animals to assess thrombogenicity of the Infant VAD system utilizing the 15-25 kg lamb model in 60 day chronic studies, 2) to assess the thrombogenic potential of the Infant VAD system in weaning mode, in which the VAD flowrate is reduced, and 3) to demonstrate reliability of 0.80 with 80% confidence for a six-month system design, with testing to demonstrate device reliability by sustained operation for periods at least twice as long as the intended use (i.e. one year).

描述（由申请人提供）：本研究的长期目标是提供一种专为需要左心室、右心室或双心室机械循环支持的婴儿设计的心室辅助装置（VAD）。 VAD 在成人中的使用已成为治疗终末期心脏病的一种可行手段，作为移植的桥梁，最近又作为目标治疗。然而，目前可用于婴儿的唯一设备要么支持持续时间有限（通常为 1 个月），要么存在显着的血栓栓塞和出血风险。该项目的具体目标是对宾夕法尼亚州婴儿 VAD 进行临床前测试。宾夕法尼亚州立大学婴儿 VAD 是一款脉冲气动泵，冲程量为 12-14 毫升。该装置在动物实验研究中显示出较低的血栓形成性，部分原因是由于 Thoratec 成人 VAD 中使用的定制 Bjork-Shiley monostrut 阀门。单支柱瓣膜不具有在聚合物三叶瓣膜中小叶后面发现的再循环区域。我们还开发了一种创新的插管设计方法，这是当前儿科 VAD 的一个缺点，但对于降低血栓栓塞风险至关重要，特别是对于婴儿和具有先天性解剖变异的患者。该项目的主要目标是对 enn State 婴儿 VAD 和新插管系统进行临床前测试（体内和体外），从而进行临床试验。次要目标是通过使用凝血、血小板功能、肾功能和外植体分析的多种测量方法，在比监管批准通常所需的更广泛的泵流量和抗凝状态下测试婴儿 VAD，来研究 VAD 系统中血栓形成和血栓栓塞的机制。这一目标代表了一个为更广泛的循环支持装置开发和动物测试方案设计做出贡献的机会，特别是在抗凝方法方面。具体目标是：1) 在动物身上进行临床前测试，以在 60 天的长期研究中利用 15-25 公斤羔羊模型评估婴儿 VAD 系统的血栓形成性，2) 评估婴儿 VAD 系统在断奶模式下的血栓形成潜力，其中 VAD 流量降低，以及 3) 证明六个月系统设计的可靠性为 0.80，置信度为 80%，并通过测试来证明装置 持续运行时间至少是预期使用时间（即一年）两倍的可靠性。