Collaborative Pediatric Critical Care Research Network

项目摘要 2005年，尤尼斯·肯尼迪·施莱佛国家儿童健康和人类发展研究所（NICHD） 建立了合作儿科重症监护研究网络（CPCCRN），以支持多机构 在重症儿童中进行的随机对照试验（RCT）和观察性研究。PL 1提案来自 犹他州大学代表新确认的CPCCRN网络提交，该网络增加到12个临床研究中心 和12个辅助站点，每年ICU入院人数超过61，000人。扩大的网络具有地理、种族/民族 和社会经济多样性，并将成为一个平台，以发展更多的研究人员，特别是年轻的临床医生， 科学家该网络将进行极具创新性的大规模多中心个性化、针对性的研究 脓毒症诱导多器官功能障碍综合征（MODS）患儿免疫调节研究 包括两项并行的、免疫表型驱动的安慰剂对照RCT，这些RCT将解决中枢假设， 个体化、病理生理学特异性免疫调节将改善脓毒症诱导的 儿童MODS这项研究建立在R 01资助的CPCCRN研究的基础上，这些研究证明了 脓毒症诱导的MODS（R 01 GM 108618 PI：Carcillo）儿童的特异性免疫表型， 免疫刺激性粒细胞巨噬细胞集落对免疫抑制的逆转作用 刺激因子（GM-CSF）（R 01 GM 094203 PI：Hall）。它还补充了正在进行的NICHD R 01资助的研究 研究小儿MODS中免疫麻痹的风险因素（R 01 HD 095976 MPI：Hall，Zuppa）。 该申请有三个具体目标：（1）实施CPCCRN组织;（2）建立一个新的组织- 制定青年临床科学家发展的战略，并提交严格的建议，以资助更多的 （3）开展个性化免疫调节治疗脓毒症所致MODS研究。的 第一项试验的重点是使用药物GM-CSF逆转免疫麻痹。第二次审判使用 适应性随机化，并侧重于药物阿那白滞素和托珠单抗的高， 在模拟中。这两项试验的主要结局将是器官功能障碍的持续时间和严重程度， 累积PELOD-2评分，次要结局将评估健康相关的生活质量和家庭功能- 在3个月和12个月时。 脓毒症诱导的MODS研究中的个性化免疫调节代表了人类的范式转变， 儿科败血症的治疗，最终超越了简单的支持性护理。我们有着独特的优势- 成功地执行这种个性化、实时、病理生理学导向的脓毒症治疗方法， 一个多样化和高度成就的研究小组的优势，以提供高影响力的科学， 我们的病人和我们的工作。

Project Summary In 2005, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Collaborative Pediatric Critical Care Research Network (CPCCRN) to support multi-institutional randomized controlled trials (RCTs) and observational studies in critically ill children. This PL1 proposal from the University of Utah is submitted on behalf of a newly configured CPCCRN network increased to 12 Clinical Sites and 12 ancillary sites with > 61,000 annual ICU admissions. The expanded network has geographic, racial/ethnic and socioeconomic diversity, and will be a platform to develop additional investigators, especially young clinician scientists. The network will conduct a highly innovative large-scale multi-center study of personalized, targeted immune modulation in children with sepsis-induced multiple organ dysfunction syndrome (MODS). The study includes two concurrent, immunophenotype-driven placebo controlled RCTs that will address the central hypoth- esis that individualized, pathophysiology-specific immunomodulation will improve outcomes from sepsis-induced MODS in children. This study builds on R01-funded CPCCRN studies that have demonstrated the existence of specific immune phenotypes among children with sepsis-induced MODS (R01GM108618 PI: Carcillo) and suc- cessful reversal of immunosuppression by administration of the immunostimulant granulocyte macrophage-colony stimulating factor (GM-CSF) (R01GM094203 PI: Hall). It also complements the ongoing NICHD R01-funded study investigating the risk factors for immunoparalysis in pediatric MODS (R01HD095976 MPI: Hall, Zuppa). This application has three specific aims: (1) Implement the CPCCRN organization; (2) Mount a comprehen- sive strategy for development of young clinician scientists and submission of rigorous proposals to fund additional research in critical care; (3) Conduct the Personalized Immunomodulation in Sepsis-induced MODS study. The first trial focuses on the use of the drug GM-CSF for the reversal of immunoparalysis. The second trial uses adaptive randomization and focuses on the drugs anakinra and tocilizumab for the targeted treatment of hyper- inflammation. The primary outcome of both trials will be duration and severity of organ dysfunction using the cumulative PELOD-2 score, and secondary outcomes will assess health related quality of life and family function- ing at 3 and 12 months. The Personalized Immunomodulation in Sepsis-Induced MODS study represents a paradigm shift in the man- agement of pediatric sepsis, finally moving beyond simple supportive care. We are uniquely positioned to suc- cessfully execute this approach to personalized, real-time, pathophysiology-directed sepsis treatment, leveraging the strengths of a diverse and highly accomplished group of investigators to deliver high-impact science to the benefit of our patients and our field.