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

• ClinicalTrials.gov Identifier: NCT01495637
• Recruitment Status: Completed
• First Posted: December 20, 2011
• Last Update Posted: February 25, 2022
• Sponsor: Mark Hall
• Collaborators: National Institute of General Medical Sciences (NIGMS); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Mark Hall, Nationwide Children's Hospital

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
Critical Injury (Trauma) in Children	Drug: GM-CSF	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 (Clinical Trial)
• 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: December 2011
• Actual Primary Completion Date: February 2022
• Actual Study Completion Date: February 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 [ Time Frame: 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 [ Time Frame: 28-days post-trauma ]
   The development of hospital-acquired infection through post-trauma day 28

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Colorado

Children's Hospital of Colorado

Aurora, Colorado, United States, 80045

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Michigan

Children's Hospital of Michigan

Detroit, Michigan, United States, 48201

United States, Missouri

Washington University / St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, Ohio

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States, 45229

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

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

More Information

• Responsible Party: Mark Hall, Professor of Pediatrics, Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT01495637
• Other Study ID Numbers: GIFT Study; R01GM094203 ( U.S. NIH Grant/Contract ); UG1HD083170 ( U.S. NIH Grant/Contract )
• First Posted: December 20, 2011
• Last Update Posted: February 25, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: A public use data set will be made available on the website of the NICHD's Collaborative Pediatric Critical Care Research Network.
• Supporting Materials: Study Protocol; Clinical Study Report (CSR)
• Time Frame: Within one year of study completion.
• Access Criteria: Access is through web request on the CPCCRN website

Keywords provided by Mark Hall, Nationwide Children's Hospital:

pediatric; trauma; critical; GM-CSF; immune

Additional relevant MeSH terms:

Wounds and Injuries; Sargramostim; Immunologic Factors; Physiological Effects of Drugs