Collaborative Pediatric Critical Care Research Network - Clinical Site

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.

Grant Number: 5PL1HD105462-05
NIH Institute/Center: NIH
Principal Investigator: JOSEPH CARCILLO