GM-CSF for Immunomodulation Following Trauma (GIFT) Study

Critical Injury (Trauma) in Children Clinical Trial

— GIFT  

Official title:

GM-CSF for Immunomodulation Following Trauma (GIFT) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01495637
• Other study ID #: GIFT Study
• Secondary ID: R01GM094203UG1HD
• Status: Completed
• Phase: Phase 4
• Start date: December 2011
• Est. completion date: February 2023

Study information

• Verified date: September 2023
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: February 2023
• Est. primary completion date: February 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Injury (Trauma) in Children
• Wounds and Injuries

Intervention

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.

Locations

Country	Name	City	State
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University / St. Louis Children's Hospital	Saint Louis	Missouri
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Nosocomial infection	The development of hospital-acquired infection through post-trauma day 28	28-days post-trauma