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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05266001
Recruitment Status : Not yet recruiting
First Posted : March 4, 2022
Last Update Posted : May 10, 2022
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Mark Hall, Nationwide Children's Hospital

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
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome Drug: GM-CSF Other: Placebo 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, 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
Estimated Study Start Date : May 30, 2022
Estimated Primary Completion Date : May 31, 2027
Estimated Study Completion Date : August 31, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

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




Primary Outcome Measures :
  1. Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05266001


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

Locations
Show Show 26 study locations
Sponsors and Collaborators
Nationwide Children's Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Responsible Party: Mark Hall, Chief, Critical Care Medicine, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT05266001    
Other Study ID Numbers: GRACE-2
First Posted: March 4, 2022    Key Record Dates
Last Update Posted: May 10, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sepsis
Toxemia
Multiple Organ Failure
Infections
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock