Single-dose Intravenous Iron Therapy for Anemia After Orthopaedic Trauma

NCT05292001 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 22441
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Blood Loss Anemia; Fracture

Keywords

intravenous iron therapy; anemia; orthopaedic trauma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Rate of anemia and anemia resolution in participants

  3 months

• Evaluation of ferritin level in response to IVIT after trauma

  3 months

• Evaluation of participant body iron stores in response to IVIT after trauma

  3 months

• Patient Reported Outcome Scores - Depression

  3 months

• Patient Reported Outcome Scores - Physical Function

  3 months

Study Arms (2)

Treatment

EXPERIMENTAL

Single infusion of low molecular weight Iron Dextran

Drug: Iron-Dextran Complex Injection [InFed]

Placebo

PLACEBO COMPARATOR

Single infusion of normal saline

Other: Saline Placebo

Interventions

Iron-Dextran Complex Injection [InFed] DRUG

single 1000mg dose

Also known as: INFeD

Treatment

Saline Placebo OTHER

Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• History of intolerance or hypersensitivity to IV iron supplementation
• Active hemorrhage requiring greater than two units (whole blood or pRBCs) transfused perioperatively
• 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

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Collins Medical Trust: collaborator
• Medical Research Foundation: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Related Publications (22)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Holm C, Thomsen LL, Norgaard A, Langhoff-Roos J. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial. Vox Sang. 2017 Apr;112(3):219-228. doi: 10.1111/vox.12477. Epub 2017 Feb 15.

  PMID: 28198084 BACKGROUND

• Strauss WE, Auerbach M. Health-related quality of life in patients with iron deficiency anemia: impact of treatment with intravenous iron. Patient Relat Outcome Meas. 2018 Aug 27;9:285-298. doi: 10.2147/PROM.S169653. eCollection 2018.

  PMID: 30214332 BACKGROUND

• Crichlow RJ, Andres PL, Morrison SM, Haley SM, Vrahas MS. Depression in orthopaedic trauma patients. Prevalence and severity. J Bone Joint Surg Am. 2006 Sep;88(9):1927-33. doi: 10.2106/JBJS.D.02604.

  PMID: 16951107 BACKGROUND

• Sharif PS, Abdollahi M. The role of platelets in bone remodeling. Inflamm Allergy Drug Targets. 2010 Dec;9(5):393-9. doi: 10.2174/187152810793938044.

  PMID: 20518723 BACKGROUND

• IRONMAN Investigators; Litton E, Baker S, Erber WN, Farmer S, Ferrier J, French C, Gummer J, Hawkins D, Higgins A, Hofmann A, De Keulenaer B, McMorrow J, Olynyk JK, Richards T, Towler S, Trengove R, Webb S; Australian and New Zealand Intensive Care Society Clinical Trials Group. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial : A randomized trial of IV iron in critical illness. Intensive Care Med. 2016 Nov;42(11):1715-1722. doi: 10.1007/s00134-016-4465-6. Epub 2016 Sep 30.

  PMID: 27686346 BACKGROUND

• DeLoughery TG. Safety of Oral and Intravenous Iron. Acta Haematol. 2019;142(1):8-12. doi: 10.1159/000496966. Epub 2019 Apr 10.

  PMID: 30970354 BACKGROUND

• Avni T, Bieber A, Grossman A, Green H, Leibovici L, Gafter-Gvili A. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc. 2015 Jan;90(1):12-23. doi: 10.1016/j.mayocp.2014.10.007. Epub 2014 Oct 30.

  PMID: 25572192 BACKGROUND

• Sultan P, Bampoe S, Shah R, Guo N, Estes J, Stave C, Goodnough LT, Halpern S, Butwick AJ. Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. 2019 Jul;221(1):19-29.e3. doi: 10.1016/j.ajog.2018.12.016. Epub 2018 Dec 19.

  PMID: 30578747 BACKGROUND

• Serrano-Trenas JA, Ugalde PF, Cabello LM, Chofles LC, Lazaro PS, Benitez PC. Role of perioperative intravenous iron therapy in elderly hip fracture patients: a single-center randomized controlled trial. Transfusion. 2011 Jan;51(1):97-104. doi: 10.1111/j.1537-2995.2010.02769.x.

  PMID: 20630042 BACKGROUND

• 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.

  PMID: 24797376 BACKGROUND

• Rampton D, Folkersen J, Fishbane S, Hedenus M, Howaldt S, Locatelli F, Patni S, Szebeni J, Weiss G. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica. 2014 Nov;99(11):1671-6. doi: 10.3324/haematol.2014.111492.

  PMID: 25420283 BACKGROUND

• Brodke DJ, Saltzman CL, Brodke DS. PROMIS for Orthopaedic Outcomes Measurement. J Am Acad Orthop Surg. 2016 Nov;24(11):744-749. doi: 10.5435/JAAOS-D-15-00404.

  PMID: 27661391 BACKGROUND

• Vincent HK, Hagen JE, Zdziarski-Horodyski LA, Patrick M, Sadasivan KK, Guenther R, Vasilopoulos T, Sharififar S, Horodyski M. Patient-Reported Outcomes Measurement Information System Outcome Measures and Mental Health in Orthopaedic Trauma Patients During Early Recovery. J Orthop Trauma. 2018 Sep;32(9):467-473. doi: 10.1097/BOT.0000000000001245.

  PMID: 30130305 BACKGROUND

• Peterson DF, McKibben NS, Hutchison CE, Lancaster K, Yang CJ, Dekeyser GJ, Friess DM, Schreiber MA, Willett NJ, Shatzel JJ, Aslan JE, Working ZM. Role of single-dose intravenous iron therapy for the treatment of anaemia after orthopaedic trauma: protocol for a pilot randomised controlled trial. BMJ Open. 2023 Mar 21;13(3):e069070. doi: 10.1136/bmjopen-2022-069070.

  PMID: 36944463 DERIVED

Related Links

• INFeD prescribing information
• PROMIS HealthMeasures website

MeSH Terms

Conditions

Fractures, Bone; Anemia

Interventions

Iron-Dextran Complex

Condition Hierarchy (Ancestors)

Wounds and Injuries; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Dextrans; Glucans; Polysaccharides; Carbohydrates

Study Officials

• Zachary M Working, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Talia D Trapalis, B.S.

CONTACT

5034945348; trapalis@ohsu.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Orthopaedic Trauma, Assistant Professor

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 23, 2022
• Study Start: June 1, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)