Single-dose Intravenous Iron Therapy for Anemia After Orthopaedic Trauma

Study Overview
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Brief Summary
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Acute blood loss in orthopaedic trauma and operative fracture care contributes substantially to perioperative anemia, which places participants at increased risk for complications including surgical site infection, cardiovascular complications, and even death. Anemia has further clinical implications in quality of life measures and is associated with fatigue, impaired physical performance, decreased exercise capacity, and mood disturbances. Thus, evaluation and treatment of perioperative anemia is critical in risk mitigation within orthopaedic surgery. The current standard of care for anemia is transfusion of packed red blood cells in only cases of severe anemia due to the substantial associated risks. A safer alternative is desirable because a critical number of participants do not meet the restrictive transfusion threshold and may suffer negative effects from anemia during recovery from the acute insult. The focus of this project is to pilot an investigation of the benefits of intravenous iron therapy (IVIT) in traumatically injured patients. Specifically, Aim I will determine feasibility of study design, recruitment, randomization, intervention implementation, blinded procedures, and retention. In Aim II, time to return to normal hemoglobin following traumatic orthopaedic injury will be assessed. With Aim III, the investigators will measure IVIT effect on participant-reported fatigue, physical function, and depression, and further determine if resolution of anemia is correlated to improvements in these measures in traumatically injured orthopaedic patients. Aim IV will focus on evaluating the role of IVIT on immune cells through a variety of novel laboratory assessments. The investigators expect this study to provide a better understanding of IVIT, which has the potential to alter providers' treatment approach of anemia in participants who sustain traumatic orthopaedic injury, thereby leading to decreased risks and improved recovery.

Official Title
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Role of Single-dose Intravenous Iron Therapy for the Treatment of Anemia in the Setting of Orthopaedic Trauma: a Pilot Study

Conditions
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Acute Blood Loss Anemia, Fracture

Intervention / Treatment
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* Drug: Iron-Dextran Complex Injection [InFed]
* Other: Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients age 18-89 admitted with a lower extremity or pelvis fracture requiring surgical stabilization Acute blood loss anemia as defined by hemoglobin concentration between 7.0-11.0g/dL within seven days post-operatively from definitive fracture stabilization during the hospital admission Exclusion criteria: History of intolerance or hypersensitivity to IV iron supplementation Active hemorrhage requiring greater than two units (whole blood or pRBCs) transfused perioperatively 1. Multiple planned operative procedures during the trauma admission, excluding orthopaedic staged procedures for the fracture meeting inclusion criterion one (such as temporizing external fixator application and washout for open fracture) in which subjects otherwise meet qualifications for enrollment after definitive stabilization Pre-existing hematologic or coagulation disorder (e.g., thalassemia, sickle cell disease, hemophilia, von Willibrand's disease, or myeloproliferative disease) Diagnosis of chronic kidney disease and/or chronic liver disease Known infection, inflammatory condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis), or malignancy Pregnancy Iron overload (defined as serum ferritin concentration ≥ 1,000ng/mL, serum iron concentration > 160μg/ dL, or serum transferrin saturation ≥ 50%) or any condition associated with iron overload (e.g., hemochromatosis and aceruloplasminemia) Patients that are tenets of the Jehovah's Witness faith Vulnerable populations including pediatric patients, geriatric populations 90 or older, incarcerated individuals, those unable to provide informed consent Inability to refrain from oral iron supplementation during study period Current or recent (within 30 days) use of immunosuppressive agents Use of any intravenous iron therapy or recombinant human erythropoietin formulation within the previous 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Interventional Model Description: Randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Single infusion of low molecular weight Iron Dextran | Drug: Iron-Dextran Complex Injection [InFed]<br>* single 1000mg dose<br>* Other names: INFeD;|
| Placebo Comparator: Placebo<br>Single infusion of normal saline | Other: Saline Placebo<br>* Normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of participant enrollment and screen failures | Appraisal of feasibility based on rate of participant enrollment per year and rate of screening failures. | 3 months | 
| Evaluation of protocol adherence | Appraisal of feasibility based on proportion of participants completing each follow up visit and proportion of missing data. | 3 months | 
| Patient Reported Outcome Scores: Fatigue | PROMIS bank v1.0 - fatigue. Computer adaptive test that measures feelings of tiredness likely to decrease one's ability to execute daily activities and function normally in family or social roles. Scored on the T-score metric (average score 50, standard deviation 10). High scores mean more of the concept being measured. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of anemia and anemia resolution in participants | Measured by the concentration of hemoglobin (oxygen carrying protein) in whole blood. This marker of anemia (defined as hemoglobin <12g/dL in females and <13.5g/dL in males) measured for inclusion assessment and to monitor for time to resolution of anemia at all study follow-up visits. | 3 months | 
| Evaluation of ferritin level in response to IVIT after trauma | Evaluated at enrollment to assess for iron overload (patients with a ferritin level ≥ 1,000ng/mL will be excluded) and tracked throughout the study to measure participants' body stores of iron. | 3 months | 
| Evaluation of participant body iron stores in response to IVIT after trauma | Assessment of body iron stores and iron carrying capacity within blood. Utilized to further define patients' anemia and iron available for functional use. | 3 months | 
| Patient Reported Outcome Scores - Depression | PROMIS bank v1.0 - depression. Computer adaptive survey administered to assess negative mood, views of self, social cognition, and decreased social engagement. Scored on the T-score metric (average score 50, standard deviation 10). High scores mean more of the concept being measured. | 3 months | 
| Patient Reported Outcome Scores - Physical Function | PROMIS bank v1.2 - physical function. Computer adaptive survey which measures self-reported capability to perform physical activities including activities of daily living. Scored on the T-score metric (average score 50, standard deviation 10). High scores mean more of the concept being measured. | 3 months | 
| Patient Reported Outcome Scores - Quality of Life | EQ-5D-5L Quality of Life Questionnaire. Instrument assesses five dimensions of health, corresponding to 3,125 possible health states that can be converted into a single 'utility' score. This will be utilized for the assessment of quality-adjusted life years (QALYs) and cost effectiveness of IVIT for the treatment of acute blood loss anemia following surgical fracture stabilization. Scored from 0-100, 100 being the best health state and 0 being the worst. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intravenous iron therapy, anemia, orthopaedic trauma