GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS

Purpose

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.

Condition

  • Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

Eligibility

Eligible Ages
Between 1 Day and 17 Years
Eligible Genders
All
Accepts 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Prospective, randomized, double-blind, placebo-controlled clinical trial
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
GM-CSF
Intravenous GM-CSF 125 mcg/m2/day x 7 days
  • Drug: GM-CSF
    same as arm/group description
Placebo Comparator
Placebo
Intravenous placebo x 7 days
  • Other: Placebo
    same as arm/group description

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Michael Bell

More Details

NCT ID
NCT05266001
Status
Recruiting
Sponsor
Nationwide Children's Hospital

Study Contact

Mark W Hall, MD
6147223438
mark.hall@nationwidechildrens.org

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.