GM-CSF for Immunomodulation Following Trauma (GIFT) Study

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.

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