Single-dose Intravenous Iron Therapy for Anemia After Orthopaedic Trauma

Official title

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

Overview

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.

Interventions

• Drug Iron-Dextran Complex Injection [InFed]
  single 1000mg dose
• Other Saline Placebo
  Normal saline

Primary outcome measures

• Rate of participant enrollment and screen failures [Time frame: 3 months]
• Evaluation of protocol adherence [Time frame: 3 months]
• Patient Reported Outcome Scores: Fatigue [Time frame: 3 months]

Secondary outcome measures (6)

• Rate of anemia and anemia resolution in participants [Time frame: 3 months]
• Evaluation of ferritin level in response to IVIT after trauma [Time frame: 3 months]
• Evaluation of participant body iron stores in response to IVIT after trauma [Time frame: 3 months]
• Patient Reported Outcome Scores - Depression [Time frame: 3 months]
• Patient Reported Outcome Scores - Physical Function [Time frame: 3 months]
• Patient Reported Outcome Scores - Quality of Life [Time frame: 3 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Oregon Health & Science University — Portland

Publications

• Shanbhag SP, Solano MA, Botros MA, Khanuja HS. Treating Preoperative Anemia to Improve Patient Outcomes After Orthopaedic Surgery. J Am Acad Orthop Surg. 2019 Dec 15;27(24):e1077-e1085. doi: 10.5435/JAAOS-D-18-00810. PMID 31149970
• Theusinger OM, Leyvraz PF, Schanz U, Seifert B, Spahn DR. Treatment of iron deficiency anemia in orthopedic surgery with intravenous iron: efficacy and limits: a prospective study. Anesthesiology. 2007 Dec;107(6):923-7. doi: 10.1097/01.anes.0000291441.10704.82. PMID 18043060
• Spahn DR. Anemia and patient blood management in hip and knee surgery: a systematic review of the literature. Anesthesiology. 2010 Aug;113(2):482-95. doi: 10.1097/ALN.0b013e3181e08e97. PMID 20613475
• Munoz M, Garcia-Erce JA, Cuenca J, Bisbe E, Naveira E; AWGE (Spanish Anaemia Working Group). On the role of iron therapy for reducing allogeneic blood transfusion in orthopaedic surgery. Blood Transfus. 2012 Jan;10(1):8-22. doi: 10.2450/2011.0061-11. Epub 2011 Nov 30. No abstract available. PMID 22153694
• Cuenca J, Garcia-Erce JA, Munoz M, Izuel M, Martinez AA, Herrera A. Patients with pertrochanteric hip fracture may benefit from preoperative intravenous iron therapy: a pilot study. Transfusion. 2004 Oct;44(10):1447-52. doi: 10.1111/j.1537-2995.2004.04088.x. PMID 15383017
• Garcia-Erce JA, Cuenca J, Munoz M, Izuel M, Martinez AA, Herrera A, Solano VM, Martinez F. Perioperative stimulation of erythropoiesis with intravenous iron and erythropoietin reduces transfusion requirements in patients with hip fracture. A prospective observational study. Vox Sang. 2005 May;88(4):235-43. doi: 10.1111/j.1423-0410.2005.00627.x. PMID 15877644
• Shin HW, Park JJ, Kim HJ, You HS, Choi SU, Lee MJ. Efficacy of perioperative intravenous iron therapy for transfusion in orthopedic surgery: A systematic review and meta-analysis. PLoS One. 2019 May 6;14(5):e0215427. doi: 10.1371/journal.pone.0215427. eCollection 2019. PMID 31059515
• Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020 Feb;287(2):153-170. doi: 10.1111/joim.13004. Epub 2019 Nov 12. PMID 31665543

Identifiers

NCT: NCT05292001 · 22441

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗