Multicenter Trial of ECMO in Children with Severe Cardiac Failure using the Cardiohelp System

项目摘要/摘要 虽然ECMO被广泛认为是严重心力衰竭儿童的标准护理，但需要 紧急生命支持，没有ECMO电路被FDA批准或批准用于儿童。初级阶段 原因是儿科临床医生长期以来一直可以不受限制地获得所需的所有设备 使用标签外的设备组装ECMO电路，而无需执行FDA批准的试验 已经通过了FDA的体外循环治疗。然而，研究表明，心脏帮助系统可以 支持患有心肺衰竭的儿童几天或几周，并发症可控。 这份重新提交的文件是对《ECMO治疗儿童的多中心试验》的良好评价的回应 使用心脏帮助系统评估该系统的安全性和有效性 为患有严重心力衰竭的儿童提供长达30天的循环支持 都失败了，临床情况预计会恶化，以支持FDA批准该系统在儿童中使用。 这项研究将在5个具有丰富经验和良好结果的中心进行，使用 儿童的心脏辅助系统。目标N是50名0至16岁(3至80公斤)的儿童接受VA ECMO。主要目标是生成所需的数据，以确保FDA批准第一个完整的 对心力衰竭儿童的ECMO回路进行研究，并确定并发症，即溶血， 与≤；10公斤相比，电路血栓/中风和肾功能衰竭在10公斤以下的儿童是可以接受的。 试用版IDE(G220250)已获得FDA的批准(附录B)。具体目标是： 具体目标1(有效性)：确定50名儿童中有30名(≥60%)是否支持 严重心力衰竭的心脏帮助系统存活到康复，耐用的VAD植入，移植，或30 根据PSOM评分，在没有因中风造成严重神经损伤的情况下提供支持的天数。 特定目标2(安全)：确定重症儿童是否需要心脏帮助系统的支持 心力衰竭经历关键的严重不良后果(症状性中风；严重溶血； 血栓栓塞或重大设备故障导致电路改变；肾功能衰竭) 指定的绩效目标(PG)： 特定目标3(监管)：生成必要的数据，以允许心脏帮助充当 支持FDA批准未来510(K)途径下的ECMO系统的谓词装置(如果值得)。 特定目标4(监管)：协调不同形式的MCS之间的SAE定义，以支持设备 无论是否有氧合器，VAD和ECMO之间的界限都是模糊的。 试验基础设施包括斯坦福大学的CCC(IDE赞助商)和波士顿儿童医院的DCC 医院。这项试验将由Sleeper、Almond和Ozment博士领导，并有互补的专业知识 (统计；监管；ECMO和危重护理)以及在试验执行方面成功合作的历史。

PROJECT SUMMARY/ABSTRACT While ECMO is widely considered the standard-of-care for children with severe cardiac failure requiring emergent life support, no ECMO circuit has ever been FDA-approved or cleared for children. The primary reason is that pediatric clinicians have long had unfettered access to all the equipment needed to assemble an ECMO circuit without performing an FDA-approval trial by using equipment off-label that has been FDA-cleared for cardiopulmonary bypass. Nevertheless, studies suggest the Cardiohelp system can support children with cardiopulmonary failure for days or weeks with manageable complications. This resubmission responds to a favorable review of the “Multicenter Trial of ECMO for Children with Severe Cardiac Failure using the Cardiohelp System”, to evaluate safety and effectiveness of the System to provide up to 30d of circulatory support to children with severe cardiac failure where other options have failed, and clinical worsening is expected, in order to support FDA clearance of the system in children. The study will be conducted at 5 centers with extensive experience and favorable outcomes using the Cardiohelp system in children. The target N is 50 children aged 0 to 16 years (3 to 80 kg) receiving VA ECMO. The primary goal is to generate the data needed to secure FDA-clearance of the first complete ECMO circuit in children with cardiac failure, and to determine whether complications, i.e., hemolysis, circuit thrombosis/stroke, and renal failure are acceptable in children ≤ 10 kg compared to those > 10 kg. The trial IDE (G220250) has Approval from the FDA (Appendix B). Specific aims are: SPECIFIC AIM 1 (Effectiveness): To determine whether ≥30 of 50 children (≥60%) supported with the Cardiohelp system for severe cardiac failure survive to recovery, durable VAD implant, transplant, or 30 days of support in the absence of severe neurological injury due to stroke as defined by the PSOM score. SPECIFIC AIM 2 (Safety): To determine whether children supported with the Cardiohelp system for severe cardiac failure experience key severe adverse outcomes (symptomatic stroke; severe hemolysis; thromboembolism or major device malfunction leading to circuit change; renal failure) within pre- specified Performance Goals (PGs): SPECIFIC AIM 3 (Regulatory): To generate the data necessary to allow the Cardiohelp to serve as a predicate device (if worthy) to support FDA clearance of future ECMO systems under the 510(k) pathway. SPECIFIC AIM 4 (Regulatory): To harmonize SAE definitions across different forms of MCS to enable device comparisons irrespective of the presence of an oxygenator, as the line between VAD and ECMO is blurring. Trial infrastructure includes a CCC at Stanford University (IDE sponsor) and a DCC at Boston Children's Hospital. The trial will be led by Drs. Sleeper, Almond and Ozment, with complementary expertise (Statistical; Regulatory; ECMO & Critical Care) and a history of successful collaboration in trial execution.