Thursday, November 21, 2024
11/21/2024
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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
