GM-CSF for Immunomodulation Following Trauma (GIFT) Study (GIFT)

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.

Study Overview

• Status: Completed
• Conditions: Critical Injury (Trauma) in Children
• Intervention / Treatment: Drug: GM-CSF

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 Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University / St. Louis Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: leukine; sargramostim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune function	To identify the lowest immunostimulatory yet tolerable dose of GM-CSF that produces lasting improvement in innate immune function in treated children.	7-days post-trauma

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nosocomial infection	The development of hospital-acquired infection through post-trauma day 28	28-days post-trauma

Collaborators and Investigators

• Sponsor: Mark Hall
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Mark W Hall, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2011
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: December 13, 2011
• First Submitted That Met QC Criteria: December 16, 2011
• First Posted (Estimated): December 20, 2011

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: trauma; pediatric; immune; GM-CSF; critical
• Additional Relevant MeSH Terms: Wounds and Injuries; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: GIFT Study; R01GM094203 (U.S. NIH Grant/Contract); UG1HD083170 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A public use data set will be made available on the website of the NICHD's Collaborative Pediatric Critical Care Research Network.
• IPD Sharing Time Frame: Within one year of study completion.
• IPD Sharing Access Criteria: Access is through web request on the CPCCRN website
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR