Single-dose Intravenous Iron Therapy for Anemia After Orthopaedic Trauma

NCT ID: NCT05292001

Last Updated: 2025-08-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-01

Study Completion Date

2026-05-31

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.

Detailed Description

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Conditions

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Acute Blood Loss Anemia Fracture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Treatment

Single infusion of low molecular weight Iron Dextran

Group Type EXPERIMENTAL

Iron-Dextran Complex Injection [InFed]

Intervention Type DRUG

single 1000mg dose

Placebo

Single infusion of normal saline

Group Type PLACEBO_COMPARATOR

Saline Placebo

Intervention Type OTHER

Normal saline

Interventions

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Iron-Dextran Complex Injection [InFed]

single 1000mg dose

Intervention Type DRUG

Saline Placebo

Normal saline

Intervention Type OTHER

Other Intervention Names

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INFeD

Eligibility Criteria

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Inclusion Criteria

1. Patients age 18-89 admitted with a lower extremity or pelvis fracture requiring surgical stabilization
2. 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

1. History of intolerance or hypersensitivity to IV iron supplementation
2. Active hemorrhage requiring greater than two units (whole blood or pRBCs) transfused perioperatively
3. 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
4. Pre-existing hematologic or coagulation disorder (e.g., thalassemia, sickle cell disease, hemophilia, von Willibrand's disease, or myeloproliferative disease)
5. Diagnosis of chronic kidney disease and/or chronic liver disease
6. Known infection, inflammatory condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis), or malignancy
7. Pregnancy
8. 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)
9. Patients that are tenets of the Jehovah's Witness faith
10. Vulnerable populations including pediatric patients, geriatric populations 90 or older, incarcerated individuals, those unable to provide informed consent
11. Inability to refrain from oral iron supplementation during study period
12. Current or recent (within 30 days) use of immunosuppressive agents
13. Use of any intravenous iron therapy or recombinant human erythropoietin formulation within the previous 30 days
Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Collins Medical Trust

OTHER

Sponsor Role collaborator

Medical Research Foundation

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role lead

Responsible Party

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Zachary Working

Director of Orthopaedic Trauma, Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Zachary M Working, MD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

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Oregon Health & Science University

Portland, Oregon, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Talia D Trapalis, B.S.

Role: CONTACT

5034945348

Facility Contacts

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Talia D Trapalis, B.S

Role: primary

503-494-5348

Zachary M Working, MD

Role: backup

4254441717

References

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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.

Reference Type BACKGROUND
PMID: 31149970 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18043060 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20613475 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22153694 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15383017 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15877644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31059515 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31665543 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28198084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30214332 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16951107 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20518723 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27686346 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 30970354 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25572192 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30578747 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20630042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24797376 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25420283 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27661391 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30130305 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36944463 (View on PubMed)

Related Links

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Other Identifiers

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22441

Identifier Type: -

Identifier Source: org_study_id

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