GM-CSF for Immunomodulation Following Trauma (GIFT) Study

Sponsor
Mark Hall (Other)
Overall Status
Completed
CT.gov ID
NCT01495637
Collaborator
National Institute of General Medical Sciences (NIGMS) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
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Study Details

Study Description

Brief Summary

The GIFT study is a prospective, multi-center, interventional trial using the drug GM-CSF for the reversal of innate immune suppression in critically injured children. The study will be conducted in two phases, a dose-finding phase then an efficacy phase. The dose-finding phase is the current active phase of the study. The central hypothesis of the study is that immunomodulation with GM-CSF will result in reduction in the risk of nosocomial infection after critical injury in high-risk children through safe, rapid, and sustained improvement in innate immune function.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

The current phase of the study is an open-label dose-finding phase in which critically injured children undergo prospective, serial immune function testing in the first few days after injury. If a subject's immune function (as measured by whole blood ex vivo LPS-induced TNF-alpha production capacity) is below a critical threshold, the subject will receive GM-CSF at a dose of 30, 62, or 125 mcg/m2 per day for three days. Enrollment is stratified by pubertal status (Tanner 1 or Tanner > 1) and by presence or absence of severe traumatic brain injury (TBI). Dose-finding is being conducted independently in each of these strata. The outcome variable for the dose-finding phase of the GIFT study is restoration of TNF-alpha production capacity and monocyte HLA-DR expression by the end of treatment, persisting to post-trauma day 7. A subsequent randomized, placebo-controlled trial with nosocomial infection as the primary outcome variable is planned once dose-finding is complete. This study is being conducted by the NICHD's Collaborative Pediatric Critical Care Research Network (CPCCRN) with Nationwide Children's Hospital as the primary site. The study design information currently displayed on this site refers to the dose-finding phase of the project.

Study Design

Study Type:
Interventional
Actual Enrollment :
108 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
GM-CSF for Immunomodulation Following Trauma (GIFT) Study
Actual Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Feb 1, 2022
Actual Study Completion Date :
Feb 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: GM-CSF

GM-CSF is given in one of four treatment regimens (three days at a dose of 30, 62, or 125 mcg/m2/day, or extended dosing at 125 mcg/m2 through post-trauma day 6) to critically injured children who demonstrate severe reduction in innate immune function on post-trauma day 1, 2, or 3.

Drug: GM-CSF
GM-CSF is to be administered IV at one of four possible dosing regimens (three days at a dose of 30, 62, or 125 mcg/m2 per day, or an extended dosing regimen of 125 mcg/m2/day through post-trauma 6) if severe innate immune suppression is identified on post-trauma days 1, 2, or 3.
Other Names:
  • sargramostim
  • leukine
  • Outcome Measures

    Primary Outcome Measures

    1. Immune function [7-days post-trauma]

      To identify the lowest immunostimulatory yet tolerable dose of GM-CSF that produces lasting improvement in innate immune function in treated children.

    Secondary Outcome Measures

    1. Nosocomial infection [28-days post-trauma]

      The development of hospital-acquired infection through post-trauma day 28

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Admission to the PICU at a GIFT study site with a primary diagnosis of blunt or penetrating trauma that occurred within the last 72 hours.

    • Age 1 - 17 years

    • Provisional Injury Severity Score (ISS) > 10

    • Presence of an endotracheal tube at the time of enrollment

    Exclusion Criteria:
    • DNR status or care team/family is considering plans for withdrawal of life-sustaining therapies.

    • Strong suspicion of injuries related to child abuse, in the opinion of the treating physician

    • Persistence (after treatment) of any of the following in the PICU before enrollment: Fixed, dilated pupils; Glasgow Coma Scale score of 3 (in the absence of neuromuscular blocking drugs); or presence of a new, severe neurologic injury at the time of enrollment which, in the opinion of the treating physician, is highly likely to lead to a diagnosis of brain death

    • Cardiopulmonary arrest requiring CPR documented by EMS or hospital personnel prior to subject identification

    • Burn injury of any kind (scald, fire, chemical)

    • Patients receiving acute or chronic immunosuppressive therapy (e.g., systemic corticosteroids, calcineurin inhibitors, mycophenolate, azathioprine) at the time of injury

    • Patients with severe leukopenia (white blood cell count < 1000 cells/mm3) at the time of injury as the result of myeloablative chemotherapy or radiation

    • Pregnancy

    • Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells, or known allergy/hypersensitivity to GM-CSF

    • Previously enrolled in the GIFT study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Colorado Aurora Colorado United States 80045
    2 Children's National Medical Center Washington District of Columbia United States 20010
    3 Children's Hospital of Michigan Detroit Michigan United States 48201
    4 Washington University / St. Louis Children's Hospital Saint Louis Missouri United States 63110
    5 Cincinnati Children's Medical Center Cincinnati Ohio United States 45229
    6 Nationwide Children's Hospital Columbus Ohio United States 43205
    7 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    8 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224

    Sponsors and Collaborators

    • Mark Hall
    • National Institute of General Medical Sciences (NIGMS)
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    Investigators

    • Principal Investigator: Mark W Hall, MD, Nationwide Children's Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mark Hall, Professor of Pediatrics, Nationwide Children's Hospital
    ClinicalTrials.gov Identifier:
    NCT01495637
    Other Study ID Numbers:
    • GIFT Study
    • R01GM094203
    • UG1HD083170
    First Posted:
    Dec 20, 2011
    Last Update Posted:
    Feb 25, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Mark Hall, Professor of Pediatrics, Nationwide Children's Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 25, 2022