Collaborative Pediatric Critical Care Research Network

儿科重症监护协作研究网络

基本信息

批准号：
10670222
负责人：
Jonathan Michael Dean
金额：
$ 241.28万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
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/10670222
关键词：
Admission activity Adult Biometry C-reactive protein Child Childhood Clinical Clinical Trials Collaborations Communication Community Healthcare Complement Critical Care Critically ill children Data Coordinating Center Development Drug usage Ethnic Origin 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 Institution 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 Placebo Control Positioning Attribute Procedures Protocols documentation Race Randomized Randomized, Controlled Trials Research Research Personnel Risk Factors Science Scientist Sepsis Severities Site Structure Supportive care Testing Time Treatment Protocols Universities Utah Work adverse outcome anakinra clinical research site expectation health assessment health related quality of life immune function immunoregulation improved improved outcome innovation meetings mortality pathogen pediatric sepsis primary outcome secondary outcome septic socioeconomic diversity targeted treatment timeline tocilizumab

项目摘要

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.

项目概要 2005 年，尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所 (NICHD) 建立儿科重症监护协作研究网络 (CPCCRN) 以支持多机构这项针对危重儿童的随机对照试验 (RCT) 和观察性研究来自 PL1 提案。犹他大学提交代表新配置的 CPCCRN 网络增加至 12 个临床站点以及 12 个辅助中心，每年 ICU 入院人数超过 61,000 人。扩大的网络具有地域、种族/民族特征。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该网络将进行高度创新的大规模、个性化、有针对性的多中心研究。脓毒症引起的多器官功能障碍综合征（MODS）儿童的免疫调节。包括两项同时进行的、免疫表型驱动的安慰剂对照随机对照试验，这将解决中心假设个体化、病理生理学特异性免疫调节将改善脓毒症引起的结果这项研究以 R01 资助的 CPCCRN 研究为基础，这些研究证明了 MODS 的存在。脓毒症诱发的 MODS 儿童的特异性免疫表型（R01GM108618 PI：Carcillo）和后续研究通过施用免疫刺激粒细胞巨噬细胞集落成功逆转免疫抑制它也补充了正在进行的 NICHD R01 资助的研究。调查儿科 MODS 免疫麻痹的危险因素（R01HD095976 MPI：Hall，Zuppa）。该应用程序有三个具体目标：（1）实施 CPCCRN 组织；（2）建立一个全面的组织；制定青年临床科学家发展的重大战略，并提交严格的建议以资助额外的资金重症监护研究；（3）开展脓毒症诱发MODS的个性化免疫调节研究。第一项试验的重点是使用 GM-CSF 药物来逆转免疫麻痹。适应性随机化，重点关注阿那白滞素和托珠单抗药物，用于靶向治疗高危人群两项试验的主要结果将是使用炎症的器官功能障碍的持续时间和严重程度。累积 PELOD-2 评分，次要结果将评估与健康相关的生活质量和家庭功能 - 3 个月和 12 个月时。脓毒症引起的 MODS 中的个性化免疫调节研究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治疗，我们具有独特的优势，能够取得成功。成功地执行这种个性化、实时、病理生理学指导的脓毒症治疗方法，利用多元化且卓有成就的研究人员团队的优势在于向世界提供高影响力的科学我们的患者和我们的领域的利益。