Collaborative Pediatric Critical Care Research Network - Clinical Site - PROJECT SUMMARY/ABSTRACT – Nationwide Children’s Hospital Nationwide Children’s Hospital (54 pediatric ICU beds and 20 cardiothoracic ICU beds with a combined annual census of >3,500 patients) and our Ancillary Site, Rainbow Babies and Children’s Hospital (24 pediatric ICU beds with an annual census of >1,600 patients), will be strong assets to the 4th cycle of the Collaborative Pediatric Critical Care Research Network (CPCCRN). The overall aim of this proposal is to advance the field of pediatric critical care medicine through the collaborative development and execution of transformative studies that benefit critically ill children. As one of the current CPCCRN sites, we (Hall – PI, Yates – Co-I, Steel – RC) have consistently been leaders in subject enrollment and project development. Dr. Hall’s Immune Surveillance Laboratory (ISL) at the Abigail Wexner Research Institute at Nationwide Children’s Hospital has served a central role in the two interventional drug trials performed by the network this cycle. These trials using the immunostimulant drug GM-CSF for the reversal of critical illness-induced immune suppression, established the safety and feasibility of multi-center, real-time immune function monitoring and modulation in our hands and, along with the current cycle’s PHENOMS sepsis phenotyping study, led us directly to the proposed study, “Personalized Immunomodulation in Sepsis-induced MODS”. This study includes two distinct, embedded, double-blind, placebo-controlled, randomized clinical trials of immunomodulation that are tailored to each subject’s prospectively-tested immune phenotype. The ISL will provide highly standardized immune function and inflammation testing kits with which the network already has extensive experience. Subjects who are found to have severe immune suppression without severe inflammation will be allocated to the “GM-CSF for Reversal of Immunoparalysis in Sepsis-induced MODS (GRACE)-2” study where they will receive GM-CSF or placebo. Subjects with moderate to severe systemic inflammation will be allocated to the “Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)” study in which subjects will be adaptively randomized to receive the anti-inflammatory drugs anakinra, tocilizumab, or placebo. This highly innovative approach is designed to ensure that the right subject receives the right immune care that matches their immunologic derangement. Our primary outcome, the cumulative PELOD-2 score over 28 days, will assess both ICU morbidity and mortality, and our secondary outcomes will assess long term morbidity and health-related quality of life. This project is an ideal platform for ancillary studies and will represent a transformative approach to sepsis care in children. Nationwide Children’s Hospital and Rainbow Babies and Children’s Hospital (Shein – PI, Slain – Co-I) are certain to be strong contributors and collaborators in the next cycle of CPCCRN and will help move our field forward through the generation of new, generalizable knowledge that will inform the treatment of critically ill children.
