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: 8502750
• 负责人: WILLIAM J WEISS
• 金额: $ 70.98万
• 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/8502750
• 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）：这项研究的长期目标是提供专门为婴儿设计的心室辅助装置（VAD），这些设备需要机械循环系统的支撑。在成年人中使用VAD已成为末期心脏病的可行手段，作为桥梁到移植物，最近作为目的地治疗。但是，当前可用于婴儿的唯一设备的支撑持续时间有限（通常为1个月），或者承担大量血栓栓塞和出血风险。该项目的具体目的是对笔状态婴儿VAD进行临床前测试。宾夕法尼亚州婴儿VAD是一种脉动气动式泵，泵有12-14毫升的中风体积。该设备在试验动物研究中表现出低的血栓形成性，部分原因是Thoratec成人VAD中使用的定制Bjork-Shiley单面阀。单一侧面阀没有在聚合物三叶瓣中的传单后面发现的再循环区域。我们还开发了一种创新的套管设计方法，该方法在当前的小儿vads中存在缺点，这对于降低血栓栓塞风险至关重要，尤其是在婴儿和先天性解剖学变异的人中。该项目的主要目的是对ENN州婴儿VAD和新的插管系统进行临床前测试（体内和体外），从而进行临床试验。第二个目标是通过在更大范围的泵流量和抗凝状态下测试婴儿VAD在VAD系统中的血栓形成，血栓栓塞的机制，而不是通常使用多个凝血，血小板功能，肾功能，肾上腺素分析所需的。该目标代表了一个机会，为循环支持装置开发和动物测试方案的设计做出贡献，尤其是在抗凝方法方面。具体目的是：1）在60天的慢性研究中使用15-25千克羔羊模型评估婴儿VAD系统的临床前测试，以评估婴儿VAD系统在Weaning模式下的血栓形成潜力，在其中，VAD流动率均可使用0.80升级为80％forse，以评估婴儿VAD系统在Weaning模式下的血栓形成潜力。持续操作的可靠性至少是预期用途的两倍（即一年）。