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

Sponsor
Nationwide Children's Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05266001
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
400
26
2
63
15.4
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Prospective, randomized, double-blind, placebo-controlled clinical trialProspective, randomized, double-blind, placebo-controlled clinical trial
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
Anticipated Study Start Date :
May 30, 2022
Anticipated Primary Completion Date :
May 31, 2027
Anticipated Study Completion Date :
Aug 31, 2027

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Day to 17 Years
Sexes Eligible for Study:
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arkansas Children's Hospital Little Rock Arkansas United States 72202
2 Children's Hospital of Los Angeles Los Angeles California United States 90027
3 University of California Los Angeles Los Angeles California United States 90095
4 Benioff Children's Hospital - Oakland Oakland California United States 64609
5 Children's Hospital of Orange County Orange California United States 92868
6 University of California - Davis Sacramento California United States 95618
7 Benioff Children's Hospital - Mission Bay San Francisco California United States 94143
8 Children's Hospital Colorado Aurora Colorado United States 80045
9 Children's National Medical Center Washington District of Columbia United States 20010
10 CS Mott Children's Hospital Ann Arbor Michigan United States 48109
11 Children's Hospital of Michigan Detroit Michigan United States 48202
12 Children's Hospital of Minnesota Minneapolis Minnesota United States 55404
13 University of Minnesota Minneapolis Minnesota United States 55455
14 Mercy Children's Hospital Kansas City Missouri United States 64108
15 Duke University Durham North Carolina United States 27705
16 Rainbow Babies and Children's Hospital Cleveland Ohio United States 44106
17 Nationwide Children's Hospital Columbus Ohio United States 43205
18 Pennsylvania State University Hershey Pennsylvania United States 17033
19 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
20 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15260
21 Medical University of South Carolina Charleston South Carolina United States 29425
22 Texas Children's Hospital Houston Texas United States 77030
23 Children's Hospital of San Antonio San Antonio Texas United States 78207
24 Primary Children's Hospital Salt Lake City Utah United States 84158
25 Virginia Commonwealth University Richmond Virginia United States 23298
26 Medical College of Wisconsin Milwaukee Wisconsin United States 53233

Sponsors and Collaborators

  • Nationwide Children's Hospital
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Mark Hall, Chief, Critical Care Medicine, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT05266001
Other Study ID Numbers:
  • GRACE-2
First Posted:
Mar 4, 2022
Last Update Posted:
May 10, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 10, 2022