Randomized Clinical Trials for Pediatric Heart Disease

描述（由申请人提供）： 南卡罗来纳州的儿童心脏项目，以MUSC为三级转诊中心，是一个全州范围的儿科心脏病专家联盟，他们照顾该州400万居民中的90%以上。该联盟具有PHN中心的所有关键要素：足够的患者数量，临床研究基础设施，受试者招募的跟踪记录，以及对假设驱动的临床研究的奉献。 事实上，这些因素使MUSC成为PHN的一个非常成功的参与者。此外，MUSC教师作为Pi参与了大量和各种各样的多中心试验或登记研究，并且该提案的Pi通常是首席研究员。MUSC教师目前也运行许多本地临床研究协议。参与所有这些方案都得到了一个专门的儿科心脏研究支持小组的支持，该小组包括RN协调员和一名行政FTE。患者数量和强大的研究基础设施的综合资源使MUSC也成为最受欢迎的学科之一。方案：接受心脏搭桥术（CPB）的新生儿术前皮质类固醇治疗的随机试验。体外循环对于心脏内手术是至关重要的，但是由体外循环引起的病理生理过程，特别是在新生儿中，在体外循环后恢复中起重要作用。在儿科心脏外科中心中，用于改善这些CPB诱导过程的类糖皮质激素给药的用途、剂量和时间表似乎差异很大，没有明确的数据提供指导。本研究的主要目的是比较术前静脉注射甲泼尼龙（IVMP）与安慰剂对新生儿CPB后36小时低心输出量状态（LCOS）或死亡的主要终点的影响。我们假设接受术前IVMP的新生儿主要终点的发生率降低。次要终点包括：36小时时的正性肌力评分、液体平衡、ICU住院参数、超声心动图测量、炎症分子水平和安全参数。该方案的一个独特方面是使用了一种新的多路复用技术，该技术允许从一毫升或更少的全血样品中分析广泛的细胞因子、基质金属蛋白酶和髓过氧化物酶。这项研究的结果应该清楚地定义术前类固醇的临床效用，并帮助确定任何观察到的效果的机制。(End抽象）。

DESCRIPTION (provided by applicant): The Children's Heart Program of South Carolina, with MUSC as the tertiary referral center, is a statewide consortium of pediatric cardiologists, who care for >90% of the 4.0 million residents in the state. This consortium has all the critical elements for a center in the PHN: adequate patient volume, clinical research infrastructure, a track record of subject enrollment, and a dedication to hypothesis driven clinical research. Indeed, these elements have allowed MUSC to be a highly successful participant in the PHN. Further, MUSC faculty have participated as Pi's in a large number and wide variety of multicenter trials or registries, and the Pi's of this proposal have often been the lead investigator. MUSC faculty also currently run numerous local clinical research protocols. Participation in all of these protocols is supported by a dedicated pediatric cardiac research support group with RN coordinators and an administrative FTE. The combined resources of patient volume and strong research infrastructure have enabled MUSC to be among the top subject enrollers as well. Protocol: Randomized Trial of Preoperative Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass (CPB). CPB is critical to corrective intracardiac surgery, but the pathophysiologic processes engendered by CPB, particularly in neonates, play an important role in post- CPB recovery. The use, doses and schedule of glucortocoid administration to ameliorate these CPB induced processes appears to be highly variable among pediatric cardiac surgical centers, without clear data to provide direction. The Primary Aim of this study is to compare the effects of preoperative intravenous methypredisolone (IVMP) to placebo on the Primary Endpoint of low cardiac output state (LCOS) or death at 36 hours following neonatal CPB. We hypothesize that neonates receiving preoperative IVMP will have a decreased incidence of the Primary Endpoint. Secondary Endpoints include: inotropic score at 36 hours, fluid balance, ICU stay parameters, echocardiographic measures, levels of inflammatory molecules, and safety parameters. One unique aspect of the protocol is the use of a novel multiplexer technology which allows analysis of a broad array of cytokines, matrix metalloproteinases and myeloperoxidase from a sample of one milliliter or less of whole blood. The results of this study should clearly define the clinical utility of preoperative steroids and help determine the mechanisms for any observed effect. (End of Abstract).