IV Iron for the Anemia of Traumatic Critical Illness

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter, Randomized, Double-blind Comparison of Intravenous Iron Supplementation to Placebo for the Treatment of Anemia of Traumatic Critical Illness

Conditions
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Trauma, ICU Anemia

Intervention / Treatment
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* Drug: Iron sucrose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Iron sucrose<br>100 mg IV TIW | Drug: Iron sucrose<br>* 100 mg IV TIW<br>* Other names: Fe sucrose;|
| Placebo Comparator: Placebo<br>Pacebo - Normal Saline | Drug: Placebo<br> <br> * Other names: control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC Transfusion | The number of participants who underwent RBC transfusion. | 42 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iron-deficient Erythropoeisis (IDE) | An elevated eZPP is diagnostic of Iron-deficient erythropoiesis (IDE) and reflects the bone marrow iron supply regardless of total body iron. | 14 Days | 
| Infection | The number of participants with at least one infection. Specific infections analyzed included VAP (Ventilator-Associated Pneumonia), bacteremia, and urinary tract infection (UTI). | 28 Days | 
| The Number of Participants Who Died |  | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, Anemia, Iron, Erythropoeisis