Clinical trial NCT01495637: GM-CSF for Immunomodulation Following Trauma (GIFT) Study
Official title: GM-CSF for Immunomodulation Following Trauma (GIFT) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Critical Injury (Trauma) in Children
Keywords: pediatric
trauma
critical
GM-CSF
immune
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2011-12-20
Enrollment: 108
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Immune function
timeFrame: 7-days post-trauma
Secondary outcomes:
measure: Nosocomial infection
timeFrame: 28-days post-trauma
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University / St. Louis Children's Hospital
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Nationwide Children's Hospital
name: Mark W Hall, MD
role: PRINCIPAL_INVESTIGATOR
References: