IV Iron for the Anemia of Traumatic Critical Illness

Nearly all trauma patients admitted to an intensive care unit (ICU) are anemic (low red blood
cell counts). Anemia is an independent risk factor for poor outcomes, including infection,
impaired wound healing, and death. Current therapies for ICU anemia are unsatisfactory: Red
blood cell (RBC) transfusion is associated with an increased risk of immune suppression,
infection, and organ failure. Furthermore, use of both hemoglobin replacement products and
erythropoietin are limited by expense as well as unfavorable side effect profiles.

One principal cause of anemia in trauma ICU patients involves disturbances in iron
metabolism. Iron is necessary to make RBCs, and a lack of iron delivered to the bone marrow
results in anemia. Trauma causes diversion of iron from the bone marrow into storage, where
it cannot participate in the generation of RBCs. This diversion of iron is caused by
inflammatory proteins released as a result of tissue injury.

Previous work by the principal investigator among ICU patients suggested a benefit to oral
iron supplementation administered in dosages similar to those used in a standard
multivitamin. However, many patients were not able to tolerate oral medications, and this
study was not specific to trauma patients. Additional research has suggested that intravenous
iron supplementation is effective in treating anemic patients with other inflammatory
conditions, such as cancer and inflammatory bowel disease. However, the benefit of
intravenous iron supplementation has never been tested among anemic ICU patients, including
trauma patients.

The current clinical trial will evaluate the risk/benefit profile of intravenous iron
supplementation among anemic trauma ICU patients. The study will take place over several
academic trauma centers with a long history of participation in translational research.

Anemia remains a devastating complication of trauma. Current treatment options are limited.
Intravenous iron supplementation represents a targeted, cost-effective solution to this
pervasive problem, the efficacy of which remains undefined.

Inclusion Criteria:

- ICU admission for trauma

- Adults (age ≥ 18 years)

- Anemia (hemoglobin < 12 g/dL)

- ≤ 72 hours from ICU admission

- Expected ICU length of stay ≥ 7 days

Exclusion Criteria:

- Active hemorrhage requiring RBC transfusion

- Iron overload (serum ferritin concentration ≥ 1,000 ng/mL) or any condition associated
with iron overload (e.g., hemochromatosis, aceruloplasminemia

- Chronic inflammatory conditions (e.g., systemic lupus erythematosis, rheumatoid
arthritis, ankylosing spondilitis)

- Pre-existing hematologic disorders (e.g., thalassemia, sickle cell disease,
hemophilia, von Willibrand's disease, myeloproliferative disease)

- Macrocytic anemia (mean corpuscular volume ≥ 100 fL)

- Current use of immunosuppressive agents including corticosteroids (e.g.,
dexamethasone, hydrocortisone, methylprednisolone, prednisone, exclusive of inhaled
corticosteroids), calcinurin inhibitors (e.g., cyclosporine, tacrolimus),
antimetabolites (e.g., azathioprine), or biologics (e.g., OKT3, thymoglobulin)

- Use of recombinant human erythropoietin formulation within the prev 30 days

- Pregnancy or lactation

- Prohibition of RBC transfusion

- Stay of ≥ 48 hours duration in the ICU of a transferring hospital

- History of intolerance or hypersensitivity to either enteral or intravenous iron

- Moribund state in which death is imminent

- Enrollment in any other clinical trial