PROJECT SUMMARY/ABSTRACT – Children’s Hospital of Michigan
The Collaborative Pediatric Critical Care Research Network (CPCCRN) is essential to advancing the science
and practice of pediatric critical care medicine. The overall aim of this site proposal is for Children’s Hospital of
Michigan (CHM), under the leadership of Kathleen Meert, MD, to continue as a clinical site in the new and
expanded CPCCRN. Dr. Meert, site-PI for the CPCCRN for the past 15 years, is a pediatric intensivist with a
wealth of clinical and translational research experience. Dr. Meert has successfully mentored many junior
investigators at CHM and other CPCCRN sites, and produced numerous scientific publications for the
CPCCRN. CHM is a free-standing, tertiary care, academic children’s hospital located in Detroit, Michigan, that
serves children and families with diverse racial, ethnic and socioeconomic backgrounds. Strengths of CHM as
a clinical site include the new (2017) Pediatric (PICU) and Cardiac (CICU) intensive care units with a total of 48
beds and over 2,000 admissions annually. CHM offers the full spectrum of pediatric and surgical subspecialty
services, and is an American College of Surgeons Level 1 Pediatric Trauma Center and an American Burn
Association Pediatric Burn Center. In addition to the resources available at CHM, Spectrum Health DeVos
Children’s Hospital in Grand Rapids, Michigan, will serve as an Ancillary Site under the leadership of Surender
Rajasekaran, MD, MPH. DeVos has a total of 32 ICU beds that include a 24-bed PICU and 8-bed CICU; these
units admit approximately 1,500 children annually. Together, CHM and DeVos will provide access to 80 ICU
beds and over 3,500 annual admissions, enabling full participation in large randomized controlled trials (RCT).
The “Personalized Immunomodulation in Sepsis-Induced Multiple Organ Dysfunction Syndrome (MODS)” trial
proposed in this application is a large RCT of personalized, targeted management of immune function in
children with sepsis-induced MODS. The trial addresses the hypothesis that immunosuppressed children will
benefit from granulocyte macrophage-colony stimulating factor (GM-CSF), and children with hyperinflammation
will benefit from targeted anti-inflammatory therapy with anakinra (recombinant IL-1 receptor antagonist) or
tocilizumab (IL-6 receptor blocking antibody). Benefit will be evaluated in terms of duration and severity of
organ dysfunction, and health-related quality of life and family functioning at 3 and 12 months. Dr. Meert and
her research team are thoroughly familiar with the CPCCRN studies on which this trial is based including
methods of sample collection and processing for immunophenotyping, dosing and administration of GM-CSF,
and collection of short- and long-term sepsis-related outcomes. Dr. Rajasekaran has research expertise in the
pathogenetic mechanisms underlying pediatric MODS making him well-suited to conduct this trial. Dr. Meert
and Dr. Rajasekaran have the full support of their respective institutions to participate in the CPCCRN, and are
strongly committed to collaboration with other CPCCRN sites and the Data Coordinating Center in conducting
the proposed research, as well as the inclusion and mentoring of junior investigators in CPCCRN activities.