Clinical trial NCT01180894: IV Iron for the Anemia of Traumatic Critical Illness
Official title: A Multicenter, Randomized, Double-blind Comparison of Intravenous Iron Supplementation to Placebo for the Treatment of Anemia of Traumatic Critical Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Trauma
ICU Anemia
Keywords: Trauma
Anemia
Iron
Erythropoeisis
Lead sponsor: Denver Health and Hospital Authority
Sponsor class: OTHER
Collaborators: name: National Trauma Research Institute
First posted: 2010-08-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to determine whether intravenous iron supplementation of anemic, critically ill trauma patients improves anemia and reduces the need for a red blood cell transfusion.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: RBC Transfusion
timeFrame: 42 Days
Secondary outcomes:
measure: Iron-deficient Erythropoeisis (IDE)
timeFrame: 14 Days
measure: Infection
timeFrame: 28 Days
measure: The Number of Participants Who Died
timeFrame: 28 Days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: New York
country: United States
facility: NewYork Presbyterian Medical Center/Weill Cornell Medical College
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: Harborview Medical Center/University of Washington
state: Washington
Study officials:
affiliation: Denver Health Medical Center, University of Colorado Health Science Center
name: Fredric M Pieracci, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pieracci FM, Stovall RT, Jaouen B, Rodil M, Cappa A, Burlew CC, Holena DN, Maier R, Berry S, Jurkovich J, Moore EE. A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness*. Crit Care Med. 2014 Sep;42(9):2048-57. doi: 10.1097/CCM.0000000000000408.