Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome
Conditions
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.
Interventions
DRUGGM-CSF
same as arm/group description
OTHERPlacebo
same as arm/group description
Sponsors
Nationwide Children's Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Prospective, randomized, double-blind, placebo-controlled clinical trial of the drug GM-CSF vs placebo
Eligibility
Sex/Gender
ALL
Age
1 Days to 17 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed