The Effects of Intravenous Iron on Mobility in Elderly Patients Following Hip Fracture Surgery (IronHip)

The Effects of Intravenous Iron on Mobility in Elderly Patients Following Hip Fracture Surgery: a Multicentre, Parallel Group, Randomised Controlled Trial

The primary aim of this clinical trial is to investigate the effects of intravenous iron on recovery in mobility compared to the pre-fracture level in patients with a hip fracture

The main questions it aims to answer are:

It is hypothesize that intravenous iron will enhance gains in mobility and hereby recovery of mobility, increase hemoglobin (Hgb), lower fatigue, have a positive effect on skeletal muscles in the weeks and months after administration.

The primary objective is to compare the effect of a single dose of ferric derisomaltose (FDI) (20 mg/kg body weight) relative to placebo on patients' recovery of functional mobility, measured as the change from baseline in the New Mobility Score.

Participants will:

- Receive either a single dose of intravenous FDI (20 mg/kg body weight) (and saline) or placebo (saline) at 1-5 days after surgery.

This trial will be conducted at three hospitals in Denmark, involving an anticipated 210 participants.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Hip Fracture
• Intervention / Treatment: Drug: Ferric Derisomaltose; Drug: Saline (NaCl 0,9 %) (placebo)

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nicolas Tekin Jones, MD; Phone Number: +4520491890; Email: nicolas.tekin.jones@regionh.dk
• Study Contact Backup: Name: Søren Overgaard, MD, DMSc; Email: soeren.overgaard@regionh.dk

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2400
    • Active, not recruiting
    • Department of Orthopedic Surgery and Traumatology, Bispebjerg, Copenhagen University Hospital
  • Herlev, Denmark, 2730
    • Recruiting
    • Department of Orthopedic Surgery and Traumatology, Herlev, Copenhagen University Hospital
    • Contact: Nicolas Tekin Jones, MD; Phone Number: +4520491890; Email: nicolas.tekin.jones@regionh.dk
    • Contact: Jens Peter Alva-Jørgensen, MD; Phone Number: + 45 3868 3868; Email: Jens.Peter.Alva-Joergensen@regionh.dk
    • Principal Investigator: Jens Peter Alva-Jørgensen, MD
  • Odense C, Denmark, 5000
    • Recruiting
    • Department of Orthopaedic Surgery, Odense and Svendborg University Hospital
    • Contact: Nicolas Tekin Jones, MD; Phone Number: +4520491890; Email: nicolas.tekin.jones@regionh.dk
    • Contact: Bjarke Viberg, MD, PhD, Professor; Phone Number: + 45 3868 3868; Email: bjarke.viberg@rsyd.dk
    • Principal Investigator: Bjarke Viberg, MD, PhD, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 65 years of age or older
2. Acute proximal femur fracture surgery
3. A hemoglobin measurement ≤6.5 mmol/L (10.5 g/dL) on day 1 to 5 postoperatively
4. Independent prefracture indoor walking ability, indoor NMS ≥ 2
5. Ability to speak and understand Danish
6. Able to provide informed consent on the participants own behalf

Exclusion Criteria:

1. Known allergy to intravenous iron
2. Residing permanently at a nursing home
3. Hematological conditions with a risk of iron overload e.g. haemochromatosis, hemosiderosis, or where alternative treatments are necessary e.g. haematological malignancies
4. Other contraindication to iron treatment, e.g. severe liver cirrhosis and hepatitis
5. Severe uncontrolled infection as assessed by the responsible clinician (e.g. bacteraemia or sepsis)
6. Plasma sodium levels below 125 or above 150 mmol/L on the day of inclusion
7. Renal replacement therapy
8. Severe dementia assessed by physician
9. Recent intravenous iron injection, 4 weeks prior to surgery
10. Patient declared terminally ill
11. Pathologic Fracture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Saline (NaCl 0,9 %) (placebo); Single dose of 100 mL isotonic sodium chloride 0.9%
Active Comparator: Active Investigational Medicinal Product	Drug: Ferric Derisomaltose; The active intervention is a single dose of Ferric Derisomaltose, 20mg/kg body weight, diluted in 100 mL isotonic sodium chloride 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New Mobility Score (NMS)	The primary outcome is to compare the effect of a single dose of FDI (20 mg/kg body weight) relative to placebo on patients' recovery of functional mobility measured with New Mobility Score. New Mobility Score is a validated patient reported outcome measurement 0-9-point score for hip fracture patients, with 9 point equal to a fully independent indoor, outdoor and during shopping walking ability and 0 point, indicating no walking ability. Higher scores indicate a better outcome.	Measured as the change from baseline (reported as pre-fracture NMS) in the New Mobility Score after 4, 6 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin		Measured at baseline, 6 and 12 weeks after intervention.
Red blood cell transfusion requirement	This will be measured by the proportion of patients who receive at least one red blood cell unit and the amounts of units per patient	Measured on postoperative day (POD) 7 and POD 30
Fatigue, assessed using the Verbal Rating Scale for Fatigue (F-VRS)	Fatigue will be assessed using the Verbal Rating Scale for Fatigue (F-VRS). This scale, ranging from 0 to 4, measures fatigue in hip fracture patients, where 0 indicates no fatigue and 4 represents extreme fatigue.	Measured at baseline, 4, 6 and 12 weeks after intervention.
Quality of life with EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L )	The EQ-5D-5L questionnaire measures health-related quality of life across five dimensions, with scores ranging from 1 (no problems) to 5 (extreme problems). Higher scores indicate worse outcomes, reflecting greater health issues.	Measured as a retrograde baseline the weeks prior to admission and at 6 and 12 weeks after intervention
EuroQol Visual Analogue Scale (EQ VAS 0-100)	The EQ VAS 0-100 (range) is a visual analogue scale where 0 represents the worst imaginable health state and 100 represents the best. Higher scores on the EQ VAS indicate a better health outcome.	Measured as a retrograde baseline the weeks prior to admission and at 6 and 12 weeks after intervention
Fear of falls measured with, Short Falls Efficacy Scale International (Short-FES-I)	Short Falls Efficacy Scale International (Short-FES-I) measures concern about falling during various activities, with scores ranging from 7 (no concern about falling) to 28 (severe concern about falling). Higher scores indicate greater concern about falling.	Measured at baseline and at 6 and 12 weeks after intervention.
30 second Sit-to-Stand-Test (STS)	Participants are encouraged to stand and fully sit as many times as possible within 30 seconds, with correct form monitored by the tester. If a participant uses their arms, they score a 0, and only correctly executed stands are counted. This test assesses a wide range of ability levels. Lower score indicates worse outcome.	Measured at baseline, 6 and 12 weeks
Activity of daily living, asessed with Barthel Index 20	Barthel 20 Index measures a patient's level of independence in daily activities, with scores ranging from 0 (complete dependence) to 20 (complete independence). Higher scores indicate a better outcome, reflecting greater independence.	Measured as a retrograde baseline and at 6 and 12 weeks after intervention
Pain, assessed using the Verbal Rating Scale for pain	Hip fracture-related pain will be assessed using the Verbal Rating Scale for Pain, which ranges from 0 to 4. A score of 0 indicates no pain, while a score of 4 represents unbearable or the worst imaginable pain	Measured at baseline and at 6 and 12 weeks after intervention
Days alive and at home up to 30 (DAH30)	The DAH30 is determined using a combination of electronic medical records (obtaining length of stay) and direct participant inquiries at the 6 week follow up	Measured at 6 weeks after intervention.
Serious adverse event (SAE)	SAE defined following the ICH - GCP guidelines	Will be assessed up to the 6 weeks follow up
Mortality	The time of death is determined using validated registry-based data, from which survival rates, as well as 30-day and 90-day mortality rates, are calculated.	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
A. Cost-effectiveness analysis	Explorative outcome A: Cost-effectiveness analysis will be made from a societal perspective including cost of FDI, hospital bed days, readmissions, outpatient visits and costs related to lost productivity of the patients (production loss). The analysis will be done according to the guidelines for health economic evaluation. The analysis will be based on data from the electronic patient records and data on the duration of patient's sick leave and absence from work from patient surveys. The main results from the analysis will be a comparison of the mean costs per patient in the intervention and the control group, the mean change in Quality Adjusted Life Years gained in the two groups (based on EQ5D) and the incremental cost-effectives ratio.	90 days post intervention
B. Physical Activity	Explorative outcome B: This outcome focuses on evaluating the effect of intravenous iron on 24-hour physical activity of patients. Physical activity will be measured using the SENS motion activity monitor. Each participant will wear the monitor for 10 days starting at the 6-week follow-up, measuring their time spent lying, sitting, standing, walking, and transitioning between these states. After 10 days, the monitor will be collected, and data will be analyzed to compare the combined amount of time spent standing and walking between the two groups. This outcome will be measured on the participants enrolled at Bispebjerg Hospital.	SENS motion activity monitor measurements will be collected 10 days after the 6-week follow-up.
C. Hand Grip Strength	Explorative outcome C: Hand grip strength will be assessed using a dynamometer measured in kilograms with a higher score representing better hand grip strength. Measured on participants enrolled at Bispebjerg Hospital. This outcome aims to determine how intravenous iron therapy influences hand grip strength, comparing the changes between the two groups.	Hand grip strength will be measured at baseline and again at the 6- and 12-week follow-ups.
D. Knee Extension Strength	Explorative outcome D: Knee extension strength will be measured using a dynamometer, measured in Nm/Kg with a higher score representing better Knee extension strength. Measured on participants enrolled at Bispebjerg Hospital. The goal is to examine the effect of intravenous iron therapy on knee extension strength between the two groups at these key points.	Knee extension strength will be measured at baseline and at 6- and 12-week follow-ups.
E. Cognition assessed using, Orientation-Memory-Concentration test (OMC)	Exploratory Outcome E: Cognition will be assessed using the Orientation-Memory-Concentration (OMC) test to examine potential differences between the groups. The OMC test range from 0-28 points, with a score of 25-27 indicating no or minimal cognitive impairment, and a score of 0-7 indicating severe impairment.	Measured at baseline, week 6 and 12 post-intervention.
F. Ferritin Levels as a Measure of Iron Status	Exploratory Outcome F: This outcome focuses on assessing the ferritin levels in both the intervention and placebo groups. Ferritin will be measured in ng/mL. The aim is to determine how intravenous iron therapy affects ferritin levels in comparison to the placebo group.	Measured at baseline and week 6 and 12 post intervention.
G: Transferrin Saturation as a Measure of Iron Status	Explorative outcome G: Transferrin saturation, measured as a percentage, will be assessed in both the intervention and placebo groups. This outcome will evaluate how transferrin saturation is affected by intravenous iron therapy compared with placebo.	Transferrin saturation will be measured at baseline, and at the 6- and 12-week follow-ups.

Collaborators and Investigators

• Sponsor: Soren Overgaard
• Collaborators: Odense University Hospital; Copenhagen University Hospital at Herlev; University Hospital Bispebjerg and Frederiksberg; Svendborg Hospital; Musculoskeletal Statistics Unit, The Parker Institute
• Investigators: Principal Investigator: Nicolas Tekin Jones, MD, Copenhagen University Hospital Bispebjerg, Department of Orthopaedic Surgery and Traumatology

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 14, 2027

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; Randomized Controlled Trial; Mobility; Hip fracture; IV Iron; Perioperative optimisation
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Hematologic Diseases; Fractures, Bone; Femoral Fractures; Hip Injuries; Hemic and Lymphatic Diseases; Hip Fractures; Anemia; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; ferric derisomaltose; Sodium Chloride
• Other Study ID Numbers: IronHip Trial; 2024-515116-42-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), will be provided to anyone who wishes to access the data.
• IPD Sharing Time Frame: Immediately following publication, no end date.
• IPD Sharing Access Criteria: Any researcher, affiliated to an established institution
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No