Collaborative Pediatric Critical Care Research Network - Clinical Site

儿科重症监护协作研究网络 - 临床网站

基本信息

批准号：
10468854
负责人：
JOSEPH A CARCILLO
金额：
$ 8.31万
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/10468854
关键词：
Accounting Acute Renal Failure with Renal Papillary Necrosis Admission activity Anti-Inflammatory Agents Biological Markers Blinded Blood Brain Injuries Cessation of life Child Child Development Child Health Childhood Cities Clinical Research Clinical Trials Clinical Trials Data Monitoring Committees Collaborations Contracts Critical Care Critical Illness Critically ill children Data Data Coordinating Center Death Records Development Diagnostic Double-Blind Method Enhancers Enrollment Faculty Functional disorder Funding Futility Future Genetic Genetic study Goals Good Clinical Practice Heart Arrest Immune Immunologic Monitoring Individual Infant Infection Infection Control Inflammation Institutes Interleukin-6 Investigation Kansas Kidney Laboratories Liquid substance Manuscripts Masks Medical center Mentors Mentorship Molecular Biology Monoclonal Antibodies Morbidity - disease rate Multiple Organ Failure National Institute of Diabetes and Digestive and Kidney Diseases National Institute of General Medical Sciences National Institute of Neurological Disorders and Stroke Nurses Organ Outcome Parental Consent Patients Pediatric Hospitals Peer Review Performance Persons Phenotype Placebos Population Positioning Attribute Principal Investigator Procedures Protocols documentation Public Health Publishing Randomized Recombinant Granulocyte-Macrophage Colony-Stimulating Factors Recombinant Interleukin-1 Recombinants Research Research Personnel Research Training Resuscitation Role SECTM1 gene Scientist Sedation procedure Sepsis Site Study Section Syringes Talents Technology Testing Universities Work anakinra burden of illness clinical research site design expectation experience feasibility trial fighting fitness immunoregulation improved innovation meetings member mortality next generation participant enrollment pathogen pediatric sepsis randomized placebo controlled trial success treatment as usual

项目摘要

PROJECT ABSTRACT/SUMMARY – University of Pittsburgh Medical Center In this PL1 application, the UPMC Children’s Hospital of Pittsburgh and our ancillary site Mercy Children’s Hospital Kansas City are applying to be two of 24 patient enrolling centers in the new Eunice Kennedy Shriver National Institutes of Child Health and Development Collaborative Pediatric Critical Care Research Network. The first large randomized double blind placebo trial proposed by the steering committee to be undertaken is the “Personalized Immunomodulation in Sepsis-induced Multiple Organ Dysfunction Syndrome” trial in children. Sepsis occurs when infection overwhelms a person. If the patient’s organs shutdown then the patient develops Multiple Organ Dysfunction which can progress to Multiple Organ Failure and death. Sepsis kills one in 5 people worldwide with children accounting for the majority of these deaths. Death from sepsis is related in part to the patient not being able to fight infection as well as not being able to control inflammation. The molecular biology revolution offers us yet unproven hope that we can temper this ancient foe using technology that was not available in the past. After attaining parental consents we will draw blood from our children with sepsis and send it to Nationwide Children’s Hospital where their immune monitoring laboratory will determine whether our children are fighting infection and controlling inflammation well enough to survive, not fighting infection well enough, or not controlling inflammation well enough. If a child is not fighting infection well enough then we will be given masked syringes that will either be placebo (usual care), or recombinant Granulocyte-Macrophage Colony Stimulating Factor (immune enhancer) that our nurse will administer in a blinded randomization schema for seven days. If a child is not able to control inflammation well enough then we will be given masked syringes that will either be placebo (usual care), or recombinant Interleukin 1 receptor antagonist protein (anti-inflammatory), or Interleukin 6 monoclonal antibody (anti-inflammatory) that our nurse will administer in a blinded adaptive randomized fashion for seven days or one day, respectively. The Data Coordinating Center and the Data Safety Monitoring Board will determine whether treatment reduces organ, as well as when to stop enrollment for benefit, harm, or futility. Our two centers are well positioned to aid the success of the new network as 1) we provide 4800 patients per year for clinical studies making this planned trial and other future trials feasible; 2) we previously performed the pivotal studies on pediatric sepsis induced multiple organ failure that have been used to design the proposed trial thus assuring our expertise; and 3) we provide a group of young investigators who will become our field’s next generation of independent investigators with mentorship attained through participation in the network.

项目摘要/摘要 – 匹兹堡大学医学中心在此 PL1 申请中，匹兹堡 UPMC 儿童医院和我们的辅助网站 Mercy Children’s 堪萨斯城医院正在申请成为新尤尼斯·肯尼迪·施赖弗 (Eunice Kennedy Shriver) 24 个患者登记中心中的两个美国国立儿童健康与发展研究所儿科重症监护合作研究网络。指导委员会提议进行的第一个大型随机双盲安慰剂试验是 “脓毒症引起的多器官功能障碍综合征的个性化免疫调节”试验当感染压倒一个人时，就会发生败血症。如果患者的器官停止运转，那么患者就会死亡。出现多器官功能障碍，可发展为多器官衰竭并导致脓毒症死亡。全世界有 5 名儿童死于败血症，其中大部分死亡与以下疾病有关。部分原因是患者无法抵抗感染以及无法控制炎症。分子生物学革命为我们提供了尚未证实的希望，即我们可以利用技术来驯服这个古老的敌人这在过去是不可能的。在获得父母同意后，我们将从孩子身上抽血。败血症并将其送往全国儿童医院，在那里他们的免疫监测实验室将确定我们的孩子是否能够很好地抵抗感染并控制炎症以生存，而不是战斗如果孩子不能很好地抵抗感染，或者不能很好地控制炎症。足够了，那么我们将获得带有掩蔽的注射器，这些注射器要么是安慰剂（常规护理），要么是重组的粒细胞巨噬细胞集落刺激因子（免疫增强剂），我们的护士将在如果孩子不能很好地控制炎症，则进行 7 天的盲法随机分组。我们将获得带有安慰剂的注射器（常规护理）或重组白细胞介素 1 受体我们的护士提供的拮抗剂蛋白（抗炎）或白细胞介素 6 单克隆抗体（抗炎）将分别以盲法自适应随机方式管理 7 天或 1 天的数据。协调中心和数据安全监测委员会将确定治疗是否减少器官，因为以及何时因利益、伤害或效用而停止注册。我们的两个中心处于有利地位，可以帮助新网络取得成功，因为 1) 我们每个中心为 4800 名患者提供服务临床研究使这项计划的试验和其他未来的试验变得可行；2) 我们之前进行过关于小儿脓毒症引起的多器官衰竭的关键研究已用于设计拟议的试验，从而确保我们的专业知识；3）我们提供了一批年轻的研究人员，他们将成为我们领域的专家通过参与网络获得指导的下一代独立调查员。