The Cardiology Clinical Research and Regulatory Group, Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Am Heart J. 2011 Sep;162(3):425-35.e6. doi: 10.1016/j.ahj.2011.05.026. Epub 2011 Jul 30.
Currently, there are no Food and Drug Administration-approved devices available that can provide long-term mechanical circulatory support to smaller children with severe heart failure as a bridge to heart transplant (HT). In recent years, the Berlin Heart EXCOR Pediatric ventricular assist device (VAD) has emerged as a potential treatment option. Systematic data on the safety and efficacy of the EXCOR are limited.
The Investigational Device Exemption (IDE) clinical study is designed to evaluate the safety and probable benefit of the EXCOR to support regulatory review of the device under the Humanitarian Device Exemption regulation. The study design and rationale are reviewed in light of the well-described challenges inherent in small population studies.
The Berlin Heart EXCOR IDE clinical study is a prospective, multicenter, single-arm, clinical cohort study. Children aged 0 to 16 years with severe heart failure (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2) due to 2-ventricle heart disease and actively listed for HT comprise the primary study cohort. The control population is a propensity-matched retrospective cohort of children supported with extracorporeal membrane oxygenation, the only bridge device available to smaller children before the EXCOR. The primary efficacy end point is survival to heart transplantation or recovery. The primary safety end point is the incidence of serious adverse events as defined by pediatric Interagency Registry for Mechanically Assisted Circulatory Support criteria. The study will enroll a total of 48 subjects in 2 cohorts based on body surface area (cohort 1 <0.7 m(2), cohort 2 0.7-1.5 m(2)) and is powered to show safety superiority to a prespecified performance goal of 0.25 serious adverse events per day of support. Children ineligible for the primary cohort will still have access to the device in a third compassionate-use cohort where adverse event data will be collected for additional safety characterization of the device.
The Berlin Heart IDE clinical study will be the first bridge-to-HT VAD study designed exclusively for children. It is anticipated that the study will provide important information on the safety and efficacy of the Berlin Heart EXCOR Pediatric in children while providing valuable lessons into the design and conduct of future VAD studies in children.
目前，尚无获得美国食品和药物管理局批准的设备可用于为患有严重心力衰竭的较小儿童提供长期机械循环支持，作为心脏移植（HT）的桥接治疗。近年来，柏林心脏 EXCOR 儿科心室辅助装置（VAD）已成为一种潜在的治疗选择。关于 EXCOR 的安全性和疗效的系统数据有限。
研究性器械豁免（IDE）临床研究旨在评估 EXCOR 的安全性和可能的益处，以为该设备根据人道主义器械豁免法规进行监管审查提供依据。根据小型人群研究中固有的明确挑战，审查了研究设计和基本原理。
柏林心脏 EXCOR IDE 临床研究是一项前瞻性、多中心、单臂、临床队列研究。患有严重心力衰竭（机构间机械辅助循环支持注册登记 2-心室疾病 profile 1 或 2）的 0 至 16 岁儿童，且积极列入 HT 名单，构成主要研究队列。对照人群是接受体外膜氧合支持的儿童的倾向匹配回顾性队列，这是在 EXCOR 之前可供较小儿童使用的唯一桥接设备。主要疗效终点是心脏移植或恢复的生存率。主要安全性终点是根据儿科机构间机械辅助循环支持标准定义的严重不良事件发生率。该研究将根据体表面积分为 2 个队列共纳入 48 名受试者（队列 1<0.7m²，队列 2 0.7-1.5m²），并具有显示优于预定支持每日 0.25 例严重不良事件的性能目标的安全性优势。不符合主要队列入选标准的儿童仍将在第三个同情使用队列中获得该设备，该队列将收集设备的不良事件数据，以进一步评估设备的安全性。
柏林心脏 IDE 临床研究将是专门为儿童设计的首例 HT 桥接 VAD 研究。预计该研究将提供有关柏林心脏 EXCOR 儿科在儿童中的安全性和疗效的重要信息，同时为未来儿童 VAD 研究的设计和实施提供宝贵经验。
