Collaborative Pediatric Critical Care Research Network

儿科重症监护协作研究网络

• 批准号: 10248812
• 负责人: Jonathan Michael Dean
• 金额: $ 241.32万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-13 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10248812
• 关键词: Address; Admission activity; Adult; Biometry; C-reactive protein; Child; Childhood; Clinical; Clinical Trials; Collaborations; Communication; Communities; Complement; Critical Care; Critically ill children; Data Coordinating Center; Development; Drug usage; Evidence based treatment; Family; Ferritin; Frequencies; Functional disorder; Funding; Geography; Granulocyte-Macrophage Colony-Stimulating Factor; Immune; Immune Targeting; Immune response; Immunologic Adjuvants; Immunologic Monitoring; Immunophenotyping; Immunosuppression; Infant; Inflammation; Intervention Studies; Laboratories; Measures; Medical; Morbidity - disease rate; Multicenter Studies; Multiple Organ Failure; National Institute of Child Health and Human Development; Observational Study; Organ; Patients; Pediatric Intensive Care Units; Performance; Pharmaceutical Preparations; Phenotype; Placebos; Positioning Attribute; Procedures; Protocols documentation; Randomized; Randomized Controlled Trials; Research; Research Personnel; Risk Factors; Science; Scientist; Sepsis; Severities; Site; Structure; Supportive care; Testing; Time; TimeLine; Treatment Protocols; Universities; Utah; Work; adverse outcome; anakinra; clinical research site; ethnic diversity; expectation; health related quality of life; immune function; immunoregulation; improved; improved outcome; innovation; meetings; mortality; pathogen; primary outcome; racial and ethnic; secondary outcome; septic; socioeconomic diversity; targeted treatment; tocilizumab

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.

项目摘要 2005年，Eunice Kennedy Shriver国家儿童健康与人类发展研究所（NICHD） 建立了协作小儿重症监护研究网络（CPCCRN）以支持多机构 重症儿童的随机对照试验（RCT）和观察性研究。该PL1提案来自 犹他大学代表一个新配置的CPCCRN网络提交到12个临床地点 和12个辅助站点，年度ICU入院率> 61,000。扩展的网络具有地理，种族/种族 和社会经济多样性，并将成为培养其他研究人员的平台，尤其是年轻的临床 科学家。该网络将对个性化，有针对性的高度创新的大规模多中心研究 败血症诱导的多器官功能障碍综合征（MODS）的儿童的免疫调节。研究 包括两个并发，免疫型驱动的安慰剂控制的RCT，这些RCT将解决中心的假设 个性化的，病理生理特异性免疫调节将改善败血症诱导的结果 儿童的mod。这项研究基于R01资助的CPCCRN研究，证明了存在 具有败血症诱导的MOD（R01GM108618 PI：Carcillo）和Suc-的儿童中的特定免疫表型 通过给予免疫刺激性粒细胞巨噬细胞殖民地进行免疫抑制的逆转 刺激因子（GM-CSF）（R01GM094203 PI：HALL）。它还符合正在进行的NICHD R01资助的研究 研究小儿MOD中免疫分析的危险因素（R01HD095976 MPI：Hall，Zuppa）。 该应用程序具有三个特定目的：（1）实施CPCCRN组织； （2）安装一个完整的 - 制定年轻临床科学家的制定战略，并提出严格的建议，以资助额外 重症监护研究； （3）在败血症诱导的MOD研究中进行个性化免疫调节。这 第一次试验侧重于使用药物GM-CSF进行免疫分析的逆转。第二次审判使用 适应性随机化，并专注于Anakinra和Tocilizumab的药物，用于针对性治疗 渗透。这两个试验的主要结果将是使用该器官功能障碍的持续时间和严重性 累积Pelod-2分数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和12个月时。 败血症诱导的mods研究中的个性化免疫调节代表了人类的范式转移 小儿败血症的染色，最后超越了简单的支持护理。我们是独特的位置，可以成功地 终止这种方法来实现个性化，实时，病理生理指导的败血症治疗，利用 潜水员和高度成就的研究人员的优势，将高影响科学提供给 我们的患者和我们的领域的好处。