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

项目总结/摘要 虽然ECMO被广泛认为是治疗严重心力衰竭儿童的标准， 紧急生命支持，没有ECMO电路曾经被FDA批准或批准用于儿童。主 原因是，儿科临床医生长期以来一直可以不受限制地使用所需的所有设备， 在未进行FDA批准试验的情况下，通过使用标签外设备组装ECMO回路， FDA批准的心肺转流手术尽管如此，研究表明， 支持心肺功能衰竭的儿童数天或数周，并发症可控。 这一重新提交回应了对“ECMO用于患有以下疾病儿童的多中心试验”的有利评价： 严重心力衰竭，使用呼吸机帮助系统”，以评价系统的安全性和有效性 为严重心力衰竭的儿童提供长达30天的循环支持， 已经失败，并且预期临床恶化，以支持FDA批准该系统用于儿童。 本研究将在5个具有丰富经验和良好结局的中心进行， 儿童的心理帮助系统。目标N为50名0至16岁（3至80 kg）接受VA治疗的儿童 体外膜肺氧合主要目标是生成确保FDA批准第一个完整的 ECMO回路在儿童心力衰竭中的应用，并确定是否有并发症，即，溶血， 与体重> 10 kg的儿童相比，体重≤ 10 kg的儿童可接受回路血栓形成/卒中和肾衰竭。 试验IDE（G220250）已获得FDA批准（附录B）。具体目标是： 具体目标1（有效性）：确定50名儿童中是否有≥30名（≥60%）支持 严重心力衰竭患者的辅助系统存活至恢复，持久的VAD植入，移植，或30 在没有由卒中引起的严重神经损伤（由PSOM评分定义）的情况下的支持天数。 具体目标2（安全性）：确定是否有儿童在严重的 心力衰竭经历关键严重不良结局（症状性卒中;严重溶血; 血栓栓塞或导致回路改变的重大器械故障;肾衰竭） 指定的绩效目标（PG）： 具体目标3（监管）：生成必要的数据，以允许数据库帮助作为 同品种器械（如有价值），以支持FDA在510（k）途径下批准未来的ECMO系统。 特定目标4（监管）：协调不同形式MCS的SAE定义，以使器械 由于VAD和ECMO之间的界限模糊，因此无论是否存在氧合器，都无法进行比较。 试验基础设施包括斯坦福大学的CCC（IDE申办者）和波士顿儿童医院的DCC 医院该试验将由Sleeper，Almond和Ozment博士领导，并具有互补的专业知识 （统计学;法规; ECMO和重症监护）以及在试验执行中的成功合作历史。

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.