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)：本研究的长期目标是提供一种专为需要左、右或双侧脑室机械循环支持的婴儿设计的脑室辅助装置(VAD)。在成人中使用VADs已成为终末期心脏病的一种可行的支持手段，作为移植的桥梁，最近还作为目的地治疗。然而，目前可供婴儿使用的唯一设备要么支持时间有限(通常为1个月)，要么存在显著的血栓栓子和出血风险。该项目的具体目标是对Pen State婴儿VAD进行临床前测试。宾夕法尼亚州立大学婴儿VAD是一种脉动气动泵，行程12-14毫升。该装置在试验性动物研究中显示出低血栓形成能力，部分原因是Thoratec成人VAD中使用的定制Bjork-Shiley单支柱瓣膜。单支柱阀不表现出聚合物三叶瓣中的叶后面的回流区。我们还开发了一种创新的插管设计方法，这是目前儿科VADs的一个缺点，对于降低血栓栓子风险至关重要，特别是在婴儿和具有先天性解剖变异的患者中。该项目的主要目标是对ENN State婴儿VAD和新的导管系统进行临床前测试(体内和体外)，从而进行临床试验。第二个目标是研究VAD系统中血栓形成和血栓栓塞的机制，方法是使用凝血、血小板功能、肾功能和外植体分析的多项指标，在比监管批准通常要求的更大范围内测试婴儿VAD的泵流和抗凝状态。这一目标为循环支持设备的开发和动物试验方案的设计提供了一个更广泛的领域，特别是在抗凝方法方面。其具体目标是：1)在动物身上进行临床前测试，以评估婴儿VAD系统的血栓形成能力；在60天的慢性研究中，利用15-25公斤的羔羊模型；2)在断奶模式下评估婴儿VAD系统的血栓形成潜力，在该模式下，VAD流量降低；3)在为期6个月的系统设计中，以80%的置信度证明可靠性为0.80，并进行测试以证明设备的可靠性，即持续运行的时间至少是预期使用时间的两倍(即一年)。