Collaborative Pediatric Critical Care Research Network - Clinical Site

儿科重症监护协作研究网络 - 临床网站

• 批准号: 10667505
• 负责人: ROBERT ALLEN BERG
• 金额: $ 17.6万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-18 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667505
• 关键词: Collaborative; Pediatric; Critical; Care; Research

PROJECT SUMMARY/ABSTRACT – Children’s Hospital of Philadelphia The Collaborative Pediatric Critical Care Research Network (CPCCRN) is essential to advancing the science and practice of pediatric critical care medicine. The overall aim of this site proposal is for Children’s Hospital of Philadelphia (CHOP), under the continued leadership of Athena Zuppa and Robert Berg, to continue as a clinical site in the new and expanded CPCCRN. Drs. Zuppa and Berg, site-PIs for the past 11 years, are pediatric intensivists with a wealth of clinical and translational research experience, who have successfully mentored many junior investigators and produced numerous scientific publications for the CPCCRN. CHOP is a free-standing, tertiary care, academic children’s hospital located in Philadelphia that serves children and families with diverse racial, ethnic, and socioeconomic backgrounds. CHOP, one of the largest children’s hospitals in the country, is a 559-bed children’s hospital with 49 pediatric medical and surgical subspecialties, a staff of over 14,585, a faculty of 860, and an annual operating budget of $3.2 billion. CHOP is home to one of the largest pediatric research programs in the country with more than $147 million in total federal awards and an annual budget of more than $404 million (FY19). The “Personalized Immunomodulation in Sepsis-Induced Multiple Organ Dysfunction Syndrome (MODS)” trial proposed in this application is a large RCT of personalized, targeted management of immune function in children with sepsis-induced MODS. The trial addresses the hypothesis that immunosuppressed children will benefit from granulocyte macrophage-colony stimulating factor (GM-CSF), and children with hyperinflammation will benefit from targeted anti-inflammatory therapy with anakinra (recombinant IL-1 receptor antagonist) or tocilizumab (IL-6 receptor blocking antibody). Benefit will be evaluated in terms of short- and long-term health-related quality of life. This study builds on CPCCRN studies that have demonstrated the existence of specific immune phenotypes among children with sepsis-induced MODS, and successful reversal of immune suppression by administration of the GM-CSF. It also complements the ongoing NICHD R01-funded study investigating the risk factors for immunoparalysis in pediatric MODS, of which Dr. Zuppa is a co-PI. This study proposes a transformative approach to personalized immune-targeted care of the septic child. Drs. Zuppa and Berg and their research team are thoroughly familiar with the CPCCRN studies on which this trial is based including methods of sample collection and processing for immunophenotyping, dosing and administration of GM-CSF, and collection of short- and long-term sepsis-related outcomes. Drs. Zuppa and Berg, and the ancillary site PI Dr. Neal Thomas have the full support of their respective institutions to participate in the CPCCRN, and are strongly committed to collaboration with other CPCCRN sites and the Data Coordinating Center, as well as the inclusion and mentoring of junior investigators in CPCCRN activities.

项目摘要/摘要 - 费城儿童医院 儿科重症监护协作研究网络 (CPCCRN) 对于推进科学发展至关重要 和儿科重症监护医学实践。该场地提案的总体目标是为儿童医院 费城 (CHOP) 在 Athena Zuppa 和 Robert Berg 的持续领导下，继续作为 新扩建的 CPCCRN 的临床中心。博士。 Zuppa 和 Berg 是过去 11 年的站点 PI 拥有丰富临床和转化研究经验的儿科重症医生，他们成功地 指导了许多初级研究人员，并为 CPCCRN 出版了大量科学出版物。斩波是 位于费城的一家独立的三级护理学术儿童医院，为儿童和儿童提供服务 具有不同种族、民族和社会经济背景的家庭。 CHOP，最大的儿童学校之一 是一家拥有 559 个床位的儿童医院，拥有 49 个儿科内科和外科专科， 员工超过 14,585 名，教职员工 860 名，年度运营预算为 32 亿美元。 CHOP 是其中之一的所在地 全国最大的儿科研究项目，联邦资助总额超过 1.47 亿美元 年度预算超过 4.04 亿美元（2019 财年）。 “脓毒症引起的个性化免疫调节 本申请中提出的“多器官功能障碍综合征（MODS）”试验是一项大型随机对照试验 对脓毒症引起的 MODS 儿童的免疫功能进行个性化、有针对性的管理。审判 解决了免疫抑制儿童将受益于粒细胞巨噬细胞集落的假设 刺激因子（GM-CSF），患有过度炎症的儿童将受益于靶向抗炎治疗 使用阿那白滞素（重组 IL-1 受体拮抗剂）或托珠单抗（IL-6 受体阻断抗体）治疗。 效益将根据短期和长期健康相关的生活质量进行评估。这项研究建立在 CPCCRN 研究表明，患有此类疾病的儿童中存在特定的免疫表型 脓毒症引起的 MODS，以及通过施用 GM-CSF 成功逆转免疫抑制。它 还补充了 NICHD R01 资助的正在进行的研究，该研究调查了免疫麻痹的危险因素 儿科 MODS，Zuppa 博士是其中的联合 PI。这项研究提出了一种变革性的个性化方法 脓毒症儿童的免疫靶向治疗。博士。 Zuppa 和 Berg 以及他们的研究团队非常熟悉 本试验所依据的 CPCCRN 研究，包括样本收集和处理方法 用于免疫表型分析、GM-CSF 的剂量和给药，以及短期和长期脓毒症相关结果的收集。博士。 Zuppa 和 Berg 以及辅助网站 PI Neal Thomas 博士得到了他们的全力支持 各机构参与 CPCCRN，并坚定致力于与其他机构合作 CPCCRN 站点和数据协调中心，以及初级研究人员的包容和指导 在 CPCCRN 活动中。