Collaborative Pediatric Critical Care Research Network - Clinical Site

项目概要/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， 超过3，500名患者）和我们的附属机构，彩虹婴儿和儿童医院（24个儿科ICU 床位，年度普查人数> 1，600名患者），将成为第四个合作周期的强大资产 儿科重症监护研究网络（CPCCRN）。该提案的总体目标是推动该领域的发展， 通过协作开发和执行变革性的儿科重症监护医学 对重症儿童有益的研究。作为目前的CPCCRN网站之一，我们（霍尔- PI，耶茨- Co-I， 钢-钢筋混凝土）一直在学科招生和项目开发的领导者。霍尔博士的免疫 全国儿童医院阿比盖尔·韦克斯纳研究所的监测实验室（ISL） 在该网络本周期进行的两项干预性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逆转危重病引起的免疫抑制， 建立了多中心、实时免疫功能监测和调节的安全性和可行性， 我们的手，沿着当前周期的PHENOMS败血症表型研究，使我们直接找到了 拟定研究，“脓毒症诱导的MODS中的个性化免疫调节”。这项研究包括两个不同的， 嵌入式、双盲、安慰剂对照、随机化免疫调节临床试验， 每个受试者的前瞻性测试的免疫表型。ISL将提供高度标准化的免疫 功能和炎症检测试剂盒，该网络已经拥有丰富的经验。的受试者 被发现有严重的免疫抑制，没有严重的炎症将被分配到“GM-CSF” 用于在脓毒症诱导的MODS中恢复免疫麻痹（GRACE）-2”研究，其中他们将接受GM-CSF 或安慰剂。患有中度至重度全身性炎症的受试者将被分配至“靶向治疗组”。 在儿科脓毒症诱导的MODS中炎症的复发（TRIPS）”研究中，受试者将 适应性随机接受抗炎药阿那白滞素、托珠单抗或安慰剂。这种高度 创新的方法旨在确保正确的受试者获得与之匹配的正确免疫护理， 他们的免疫紊乱我们的主要结果，28天内的累积PELOD-2评分， 评估ICU发病率和死亡率，我们的次要结局将评估长期发病率和 健康相关的生活质量。该项目是辅助研究的理想平台， 儿童脓毒症护理的变革性方法。全国儿童医院和彩虹婴儿， 儿童医院（Shein - PI，Slain - Co-I）肯定会成为下一个项目的强大贡献者和合作者。 CPCCRN的周期，并将有助于推动我们的领域通过新的，可推广的知识的产生前进 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.