Phase IIB Transmural Systems Transcatheter Cavopulmonary Bypass Endograft

项目摘要 Anterior Systems LLC开发了一种专用的经导管腔静脉旁路覆膜支架 （TCBE），将允许介入心脏病专家治疗功能性单心室出生的儿童 (FSV)紫绀型先天性心脏病的一种。出生时患有FSV的儿童占所有FSV患者的7.7%。 先天性心脏病（CHD）。在美国，每年约有2000名儿童出生时患有FSV。FSV是 适用于几种复杂CHD的总称，包括左心发育不良综合征（HLHS）， 肺动脉闭锁伴室间隔完整、三尖瓣闭锁和房室管不平衡， 还有其他的如果不进行治疗，FSV患者一年的精算生存率仅为53 10岁时为42%。然而，姑息性外科手术的发展明显地 提高了FSV患者的生存率，但这些手术和随后的长期住院， 心血管重症监护病房对FSV患者的死亡率和发病率有显著影响。一个不那么 对于这些外科手术，迄今为止还没有侵入性临床替代方案。经导管 替代方案将提供降低死亡率和发病率以及减少住院时间的可能性， 相关费用。因此，临床上迫切需要一种有效的经皮方法来治疗FSV。在 根据先前的第二阶段合同，由美国国防系统公司设计的TCBE旨在建立一个双向的 上级腔静脉和右肺动脉之间的Glenn分流。TCBE的设计 在血管实验室模型以及急性和慢性良好实验室中进行了优化和广泛测试 实践（GLP）猪实验。TCBE在这些方面表现出出色的效率和安全性， 实验该IIB期项目的目标是在临床试验中利用Atriural的TCBE来测试 安全性和治疗价值。早期可行性研究（EFS）将是这方面的重点 第二阶段奖。医疗系统将在罗伯特·J·莱德曼博士的专业知识的指导下， NHLBI和Rady儿童医院的Kanishka Ratnayaka博士，John摩尔博士，John Nigro和Howaida El-Said博士，都是Rady儿童医院的医生，他们将协助运行和进行 临床研究。EFS完成的目标将通过执行以下具体 目的：1）按照良好生产规范（GMP）制造并灭菌一批TCBE器械， 临床前测试并支持EFS; 2）执行临床前测试以证明TCBE设计 质量标准符合设计要求，生成报告提交给食品药品监督管理局 (FDA)作为试验用器械豁免（IDE）包的一部分，并获得启动EFS的批准; 和3）EFS的完整入组（最多n=10个受试者）。这些拟议的具体目标是以下方面的重要步骤： 将TCBE商业化（通过未来的人道主义设备豁免试验），这将是唯一的设备 在市场上有目的地为FSV创建。

PROJECT SUMMARY Transmural Systems LLC has developed a purpose-built Transcatheter Cavopulmonary Bypass Endograft (TCBE) that will allow for interventional cardiologists to treat children born with functional single ventricle (FSV), a form of cyanotic congenital heart disease. Children born with FSV represent 7.7% of all patients with congenital heart defects (CHD). In the United States, about 2000 children are born with FSV each year. FSV is an umbrella term applied to several complex CHDs, which includes Hypoplastic Left Heart Syndrome (HLHS), Pulmonary Atresia with Intact Ventricular Septum, Tricuspid Atresia, and Unbalanced Atrioventricular Canal, among others. Without treatment, the actuarial survival rates of patients with FSV are only 53% at one year and 42% at ten years of age. The development of palliative surgical procedures, however, has markedly improved the survival of patients with FSV, but these surgeries and subsequent lengthy stays in the cardiovascular intensive care unit contribute significantly to mortality and morbidity of FSV patients. A less invasive clinical alternative has not to date been available for these surgical procedures. A transcatheter alternative would offer the possibility of reduced mortality and morbidity, as well as reduced hospital stays and related costs. Thus, there is an urgent clinical need for an effective percutaneous approach to treating FSV. In a previous Phase II contract, Transmural Systems engineered the TCBE, intended to create a Bi-directional Glenn shunt between the Superior Vena Cava and Right Pulmonary Artery. The TCBE design has been optimized and extensively tested in vascular bench models and in acute and chronic Good Laboratory Practices (GLP) swine experiments. The TCBE has performed with excellent efficiency and safety in these experiments. The goal for this Phase IIB project is to utilize Transmural’s TCBE in a clinical trial to test the safety and therapeutic value in treating FSV patients. An early feasibility study (EFS) will be the focus of this Phase IIB Award. Transmural Systems will be significantly guided by the expertise of Dr. Robert J. Lederman of the NHLBI, Dr. Kanishka Ratnayaka of the NHLBI and Rady Children’s Hospital, Dr. John Moore, Dr. John Nigro, and Dr. Howaida El-Said, all of Rady Children's Hospital, who will assist in running and conducting clinical studies. The goal of EFS completion will be achieved through the execution of the following Specific Aims: 1) manufacture and sterilize a batch of TCBE devices utilizing Good Manufacturing Practices (GMP) for preclinical testing and to support EFS; 2) execute preclinical testing to demonstrate the TCBE design specifications meet the design requirements, generate a report to submit to Food and Drug Administration (FDA) as part of an Investigational Device Exemption (IDE) package, and receive approval to start the EFS; and 3) complete enrollment of EFS (up to n=10 subjects). These proposed Specific Aims are vital steps in commercializing the TCBE (through a future Humanitarian Device Exemption trial) that will be the only device on the market purposefully created for FSV.