Phase IIB Transmural Systems Transcatheter Cavopulmonary Bypass Endograft

IIB 期透壁系统经导管腔肺旁路内移植物

基本信息

批准号：
10626898
负责人：
Nasser Rafiee
金额：
$ 55.13万
依托单位：
TRANSMURAL SYSTEMS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10626898
关键词：
10 year old Acute Address Anatomic Models Animals Award Blood Vessels Bypass Cardiac Surgery procedures Child Chronic Clinical Clinical Research Clinical Trials Common Ventricle Communication Complex Congenital Heart Defects Contractor Contracts Data Development Device Designs Devices Documentation Engineering Enrollment Environment Family suidae Feasibility Studies Funding Funding Opportunities Future Goals Good Manufacturing Process Human Hypoplastic Left Heart Syndrome Intervention Length of Stay Marketing Medical Device Designs Modeling Morbidity - disease rate National Heart, Lung, and Blood Institute Operative Surgical Procedures Outcome Palliative Surgery Patients Pediatric Hospitals Phase Physicians Preclinical Testing Preparation Process Protocols documentation Pulmonary artery structure Recording of previous events Reporting Running Safety Shunt Device Specific qualifier value Sterilization Summary Reports Superior vena cava structure Survival Rate System Testing Therapeutic Training Tricuspid Atresia United States United States Food and Drug Administration Work cardiac intensive care unit clinical lot clinical research site commercialization congenital heart disorder cost design design verification experimental study follow-up good laboratory practice human subject improved industry partner innovation manufacture mortality novel patient population pre-clinical pulmonary atresia with intact ventricular septum research clinical testing safety testing

项目摘要

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.

项目概要 Transmural Systems LLC 开发了一种专用的经导管腔肺旁路内移植物（TCBE）将允许介入心脏病专家治疗出生时具有功能性单心室的儿童 (FSV)，一种紫绀型先天性心脏病，出生时患有 FSV 的儿童占所有患有 FSV 的患者的 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。适用于多种复杂先心病的总称，其中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，如果不进行治疗，FSV 患者一年的精算生存率仅为 53%。然而，姑息性外科手术的发展已显着提高。改善了 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着影响。迄今为止，还没有可用于这些外科手术的侵入性临床替代方案。替代方案将有可能降低死亡率和发病率，并减少住院时间和因此，临床迫切需要一种有效的经皮方法来治疗 FSV。在之前的第二阶段合同中，Transmural Systems 设计了 TCBE，旨在创建一个双向上腔静脉和右肺动脉之间的格伦分流 TCBE 设计。在血管台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 TCBE 在这些猪实验中表现出了出色的效率和安全性。该 IIB 期项目的目标是在临床试验中利用 Transmural 的 TCBE 来测试。治疗 FSV 患者的安全性和治疗价值将是此次研究的重点。 IIB 期奖将在 Robert J. Lederman 博士的专业知识的指导下进行。 NHLBI 的 Kanishka Ratnayaka 博士、NHLBI 和 Rady 儿童医院的 John Moore 博士、John 博士 Nigro 和拉迪儿童医院的 Howaida El-Said 博士将协助运营和开展 EFS 完成的目标将通过执行以下具体措施来实现。目标：1) 利用良好生产规范 (GMP) 制造一批 TCBE 设备并对其进行灭菌，以用于临床前测试并支持 EFS；2) 执行临床前测试以演示 TCBE 设计规格符合设计要求，生成报告提交食品药品监督管理局 (FDA) 作为研究器械豁免 (IDE) 计划的一部分，并获得启动 EFS 的批准； 3) 完成 EFS 注册（最多 n=10 名受试者）。这些拟议的具体目标是实现这一目标的重要步骤。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专门为 FSV 创建的市场上。