search
Back to results

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

Primary Purpose

Critical Injury (Trauma) in Children

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
GM-CSF
Sponsored by
Mark Hall
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Critical Injury (Trauma) in Children focused on measuring pediatric, trauma, critical, GM-CSF, immune

Eligibility Criteria

1 Year - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital of Colorado
  • Children's National Medical Center
  • Children's Hospital of Michigan
  • Washington University / St. Louis Children's Hospital
  • Cincinnati Children's Medical Center
  • Nationwide Children's Hospital
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GM-CSF

Arm Description

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.

Outcomes

Primary Outcome Measures

Immune function
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

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

Full Information

First Posted
December 13, 2011
Last Updated
September 12, 2023
Sponsor
Mark Hall
Collaborators
National Institute of General Medical Sciences (NIGMS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
search

1. Study Identification

Unique Protocol Identification Number
NCT01495637
Brief Title
GM-CSF for Immunomodulation Following Trauma (GIFT) Study
Acronym
GIFT
Official Title
GM-CSF for Immunomodulation Following Trauma (GIFT) Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 2011 (Actual)
Primary Completion Date
February 2022 (Actual)
Study Completion Date
February 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mark Hall
Collaborators
National Institute of General Medical Sciences (NIGMS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Injury (Trauma) in Children
Keywords
pediatric, trauma, critical, GM-CSF, immune

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
108 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GM-CSF
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GM-CSF
Other Intervention Name(s)
sargramostim, leukine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Immune function
Description
To identify the lowest immunostimulatory yet tolerable dose of GM-CSF that produces lasting improvement in innate immune function in treated children.
Time Frame
7-days post-trauma
Secondary Outcome Measure Information:
Title
Nosocomial infection
Description
The development of hospital-acquired infection through post-trauma day 28
Time Frame
28-days post-trauma

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark W Hall, MD
Organizational Affiliation
Nationwide Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Washington University / St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

GM-CSF for Immunomodulation Following Trauma (GIFT) Study

We'll reach out to this number within 24 hrs