GM-CSF for Immunomodulation Following Trauma (GIFT) Study

NCT ID: NCT01495637

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2023-02-28

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.

Conditions

Critical Injury (Trauma) in Children

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GM-CSF

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

sargramostim; leukine

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Mark Hall

OTHER

Sponsor Role: lead

Responsible Party

Mark Hall

Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mark W Hall, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Children's Hospital of Colorado

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Washington University / St. Louis Children's Hospital

St Louis, Missouri, United States

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

R01GM094203

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1HD083170

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GIFT Study

Identifier Type: -

Identifier Source: org_study_id