Collaborative Pediatric Critical Care Research Network - Clinical Site

项目摘要/摘要-全国儿童医院 全国儿童医院(54张儿科ICU床位和20张心胸ICU床位，每年合计 3,500名患者的人口普查)和我们的辅助站点彩虹婴儿和儿童医院(24个儿科ICU 具有每年1,600名患者普查的床位)，将成为协作的第四个周期的强大资产 儿科重症监护研究网络(CPCCRN)。这项建议的总体目标是推动这一领域的发展 通过合作开发和执行变革性的儿科重症护理医学 使危重儿童受益的研究。作为目前CPCCRN的站点之一，我们(Hall-Pi，Yates-Co-i， Steel-RC)在学科招生和项目开发方面一直处于领先地位。霍尔医生的免疫力 国家儿童医院阿比盖尔·韦克斯纳研究所的监测实验室(ISL)已经 在该网络在本周期进行的两项介入药物试验中发挥了核心作用。这些试验 使用免疫刺激药物GM-CSF逆转危重疾病引起的免疫抑制， 建立了多中心、实时免疫功能监测和调控的安全性和可行性 我们的双手，以及当前周期的物候败血症表型研究，直接将我们带到了 建议的研究，“脓毒症诱导的多器官功能障碍综合征的个性化免疫调节”。这项研究包括两个截然不同的 嵌入式、双盲、安慰剂对照、随机免疫调节临床试验，专为 每个受试者的前瞻性测试免疫表型。ISL将提供高度标准化的免疫 功能和炎症测试套件，该网络已经拥有丰富的经验。受试者 被发现有严重免疫抑制而没有严重炎症的人将被分配给“GM-CSF 用于逆转脓毒症诱导的MODS的免疫麻痹(GRACE)-2“他们将接受GM-CSF的研究 或者安慰剂。患有中度到重度全身炎症的受试者将被分配到 儿科脓毒症诱导的多器官功能障碍综合征(TRIPS)的炎症逆转“研究中，受试者将 适应性随机接受抗炎药Anakinra、tocilizumab或安慰剂。如此之高 创新的方法旨在确保合适的受试者接受匹配的合适的免疫护理 他们的免疫紊乱。我们的主要结果，28天内的累积PELOD-2评分将 评估ICU发病率和死亡率，我们的次要结果将评估长期发病率和死亡率 与健康相关的生活质量。该项目是辅助研究的理想平台，将代表 儿童败血症护理的变革性方法。全国儿童医院和彩虹婴儿医院 儿童医院(Shin-Pi，Slain-Co-I)肯定会在未来成为强有力的贡献者和合作者 CPCCRN的循环，并将通过产生新的、可概括的知识来帮助推动我们的领域向前发展 这将为危重儿童的治疗提供信息。

PROJECT SUMMARY/ABSTRACT – Nationwide Children’s Hospital Nationwide Children’s Hospital (54 pediatric ICU beds and 20 cardiothoracic ICU beds with a combined annual census of >3,500 patients) and our Ancillary Site, Rainbow Babies and Children’s Hospital (24 pediatric ICU beds with an annual census of >1,600 patients), will be strong assets to the 4th cycle of the Collaborative Pediatric Critical Care Research Network (CPCCRN). The overall aim of this proposal is to advance the field of pediatric critical care medicine through the collaborative development and execution of transformative studies that benefit critically ill children. As one of the current CPCCRN sites, we (Hall – PI, Yates – Co-I, Steel – RC) have consistently been leaders in subject enrollment and project development. Dr. Hall’s Immune Surveillance Laboratory (ISL) at the Abigail Wexner Research Institute at Nationwide Children’s Hospital has served a central role in the two interventional drug trials performed by the network this cycle. These trials using the immunostimulant drug GM-CSF for the reversal of critical illness-induced immune suppression, established the safety and feasibility of multi-center, real-time immune function monitoring and modulation in our hands and, along with the current cycle’s PHENOMS sepsis phenotyping study, led us directly to the proposed study, “Personalized Immunomodulation in Sepsis-induced MODS”. This study includes two distinct, embedded, double-blind, placebo-controlled, randomized clinical trials of immunomodulation that are tailored to each subject’s prospectively-tested immune phenotype. The ISL will provide highly standardized immune function and inflammation testing kits with which the network already has extensive experience. Subjects who are found to have severe immune suppression without severe inflammation will be allocated to the “GM-CSF for Reversal of Immunoparalysis in Sepsis-induced MODS (GRACE)-2” study where they will receive GM-CSF or placebo. Subjects with moderate to severe systemic inflammation will be allocated to the “Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)” study in which subjects will be adaptively randomized to receive the anti-inflammatory drugs anakinra, tocilizumab, or placebo. This highly innovative approach is designed to ensure that the right subject receives the right immune care that matches their immunologic derangement. Our primary outcome, the cumulative PELOD-2 score over 28 days, will assess both ICU morbidity and mortality, and our secondary outcomes will assess long term morbidity and health-related quality of life. This project is an ideal platform for ancillary studies and will represent a transformative approach to sepsis care in children. Nationwide Children’s Hospital and Rainbow Babies and Children’s Hospital (Shein – PI, Slain – Co-I) are certain to be strong contributors and collaborators in the next cycle of CPCCRN and will help move our field forward through the generation of new, generalizable knowledge that will inform the treatment of critically ill children.