GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS (GRACE-2)

Nationwide Children's Hospital

Status and phase: Terminated; Phase 3

Conditions: Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

Treatments: Drug: GM-CSF; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05266001

GRACE-2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 141 patients

Sex: All

Ages: 1 day to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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141 participants in 2 patient groups, including a placebo group

GM-CSF

Active Comparator group

Description:

Intravenous GM-CSF 125 mcg/m2/day x 7 days

Treatment:

Drug: GM-CSF

Placebo

Placebo Comparator group

Description:

Intravenous placebo x 7 days

Treatment:

Other: Placebo