Collaborative Pediatric Critical Care Research Network

项目摘要 2005年，尤尼斯·肯尼迪·施莱弗国家儿童健康和人类发展研究所(NICHD) 建立了儿科重症监护协作研究网络(CPCCRN)，以支持多机构 危重儿童随机对照试验和观察性研究。这份PL1提案来自 犹他大学代表一个新成立的由fi领导的CPCCRN网络提交，增加到12个临床站点 和12个附属地点，每年有6.1万名ICU入院者。扩大后的网络有地理、种族/民族 和社会经济多样性，并将成为培养更多研究人员，特别是年轻临床医生的平台 科学家。该网络将进行高度创新的大规模多中心个性化、有针对性的研究 脓毒症引起的多器官功能障碍综合征(MODS)患儿的免疫调节。这项研究 包括两个并行的、免疫表型驱动的安慰剂对照RCT，将解决中枢假设- 研究表明，个体化、病理生理学特异性的fic免疫调节将改善脓毒症诱导的预后。 儿童的多器官功能障碍。这项研究建立在R01资助的CPCCRN研究的基础上，这些研究证明了 脓毒症诱导的多器官功能障碍综合征(R01GM108618 PI：Carcillo)患儿的特异性fic免疫表型 免疫刺激剂粒细胞-巨噬细胞集落成功逆转免疫抑制 刺激因子(GM-CSF)(R01GM094203 PI：Hall)。它也是正在进行的由NICHD R01资助的研究的补充 探讨儿童MODS免疫麻痹的危险因素(R01HD095976 MPI：Hall，Zuppa)。 这个应用程序有三个特殊的fic目标：(1)实现CPCCRN的组织；(2)安装一个综合- 积极发展年轻临床医生科学家的战略，并提交严格的建议，以资助额外的 在重症监护方面的研究；(3)在脓毒症诱导的MODS研究中进行个性化免疫调节。这个 fi首个试验的重点是使用GM-csf药物逆转免疫麻痹。第二次试验使用 适应性随机化，重点是阿那金拉和托西珠单抗靶向治疗高血压 在fl中。这两项试验的主要结果将是使用 累积的PELOD-2评分和次要结果将评估与健康相关的生活质量和家庭功能- 在3个月和12个月时。 脓毒症诱导的多器官功能障碍综合征的个性化免疫调节研究代表了人类- 儿科败血症的治疗，fi最终超越了简单的支持性护理。我们处于独特的地位，可以起诉- 成功地将这种方法用于个性化、实时、病理生理学导向的脓毒症治疗，利用 一个多样化和高度成功的调查小组的优势是向 我们的病人和我们的fifi。

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.