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

NCT ID: NCT05266001

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-14

Study Completion Date

2024-12-01

Brief Summary

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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

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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.

Conditions

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Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, randomized, double-blind, placebo-controlled clinical trial of the drug GM-CSF vs placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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GM-CSF

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

Group Type ACTIVE_COMPARATOR

GM-CSF

Intervention Type DRUG

same as arm/group description

Placebo

Intravenous placebo x 7 days

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

same as arm/group description

Interventions

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GM-CSF

same as arm/group description

Intervention Type DRUG

Placebo

same as arm/group description

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

1 Day

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Mark Hall

Chief, Critical Care Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

Benioff Children's Hospital - Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

University of California - Davis

Sacramento, California, United States

Site Status

Benioff Children's Hospital - Mission Bay

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

CS Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Children's Hospital of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mercy Children's Hospital

Kansas City, Missouri, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Pennsylvania State University

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Children's Hospital of San Antonio

San Antonio, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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GRACE-2

Identifier Type: -

Identifier Source: org_study_id