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.
