ICU Anemia, Trauma
Conditions
Keywords
Trauma, Anemia, Iron, Erythropoeisis
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.
Interventions
DRUGIron sucrose
100 mg IV TIW
DRUGPlacebo
Sponsors
National Trauma Research Institute
Denver Health and Hospital Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RBC Transfusion | 42 Days | The number of participants who underwent RBC transfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Iron-deficient Erythropoeisis (IDE) | 14 Days | An elevated eZPP is diagnostic of Iron-deficient erythropoiesis (IDE) and reflects the bone marrow iron supply regardless of total body iron. |
| Infection | 28 Days | The number of participants with at least one infection. Specific infections analyzed included VAP (Ventilator-Associated Pneumonia), bacteremia, and urinary tract infection (UTI). |
| The Number of Participants Who Died | 28 Days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iron Sucrose 100 mg IV TIW
Iron sucrose: 100 mg IV TIW | 75 |
| Placebo Placebo
100 mg Normal saline | 75 |
| Total | 150 |
Baseline characteristics
| Characteristic | Placebo | Iron Sucrose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Categorical >=65 years | 5 Participants | 13 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants | 56 Participants | 122 Participants |
| Age, Continuous | 40.4 years | 41.6 years | 41.0 years |
| Region of Enrollment United States | 75 participants | 75 participants | 150 participants |
| Sex: Female, Male Female | 29 Participants | 17 Participants | 46 Participants |
| Sex: Female, Male Male | 46 Participants | 58 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 75 | 0 / 75 |
| serious Total, serious adverse events | 7 / 75 | 2 / 75 |
Outcome results
Primary
RBC Transfusion
The number of participants who underwent RBC transfusion.
Time frame: 42 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iron Sucrose | RBC Transfusion | 47 participants |
| Placebo | RBC Transfusion | 55 participants |
Secondary
Infection
The number of participants with at least one infection. Specific infections analyzed included VAP (Ventilator-Associated Pneumonia), bacteremia, and urinary tract infection (UTI).
Time frame: 28 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iron Sucrose | Infection | 1 participants |
| Placebo | Infection | 1 participants |
Secondary
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.
Time frame: 14 Days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Iron Sucrose | Iron-deficient Erythropoeisis (IDE) | 118 micro mol: mol heme |
| Placebo | Iron-deficient Erythropoeisis (IDE) | 118 micro mol: mol heme |
Secondary
The Number of Participants Who Died
Time frame: 28 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iron Sucrose | The Number of Participants Who Died | 7 participants |
| Placebo | The Number of Participants Who Died | 2 participants |