GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
- Conditions
- Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome
- Interventions
- Other: Placebo
- Registration Number
- NCT05266001
- Lead Sponsor
- Nationwide Children's Hospital
- Brief Summary
The GRACE-2 study is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation.
- Detailed Description
The GRACE-2 study is a is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation. Eligible subjects will undergo centralized immunophenotyping on MODS Day 2. Those who are found to have immunoparalysis (a whole blood LPS-induced TNF-alpha production capacity \< 200 pg/ml) with mild to moderate inflammation (serum ferritin level \< 2000 ng/ml) will be randomized to receive intravenous (IV) GM-CSF at a dose of 125 mcg/m2/day x 7 days or placebo. The primary outcome variable is the cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score. Secondary outcomes include measures of health-related quality of life and function status at 3 months from randomization.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 141
- ≥ 40 weeks corrected gestational age to < 18 years; AND
- Admission to the PICU or CICU; AND
- Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND
- Documented or suspected infection as the MODS inciting event.
- Weight <3kg; OR
- Limitation of care order at the time of screening; OR
- Patients at high likelihood of progression to brain death in opinion of the clinical team; OR
- Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR
- History of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia; OR
- Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR
- Peripheral white blood cell count < 1,000 cells/mm3 as the result of myeloablative therapy OR receipt of myeloablative therapy within the previous 14 days; OR
- Known allergy to GM-CSF; OR
- Known pregnancy; OR
- Lactating females; OR
- Receipt of anakinra or GM-CSF within the previous 28 days; OR
- Resolution of MODS by MODS Day 2; OR
- Previous enrollment in the GRACE-2 study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Intravenous placebo x 7 days GM-CSF GM-CSF Intravenous GM-CSF 125 mcg/m2/day x 7 days
- Primary Outcome Measures
Name Time Method Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score 28 days from randomization Cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score through 28 days post-randomization. The range of PELOD-2 score for a given day is 0 - 33 with a higher number being worse.
- Secondary Outcome Measures
Name Time Method 3-month health-related quality of life 3 months post-randomization Change in Pediatric Quality of Life inventory (PedsQL) score from baseline to 3 months post-randomization. The range of PedsQL scores is from 0 - 100, with higher values corresponding to better quality of life.
3-month functional status 3 months post-randomization Change in Functional Status Score from baseline to 3 months post-randomization. The range of possible FSS score for a given subject is 6 - 30 with a higher score indicating worse function.
Trial Locations
- Locations (25)
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Benioff Children's Hospital - Oakland
🇺🇸Oakland, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
University of California - Davis
🇺🇸Sacramento, California, United States
Benioff Children's Hospital - Mission Bay
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
CS Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Children's Hospital of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mercy Children's Hospital
🇺🇸Kansas City, Missouri, United States
Duke University
🇺🇸Durham, North Carolina, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Pennsylvania State University
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States