Hyperbaric Oxygen Therapy as Adjunctive Treatment for Fracture-Related Infection (SOLDIER)

Supplementary Oxygen Therapy After Limb Debridement and Reconstruction Surgery in Infected Extremity Fractures (SOLDIER): a Pilot, Non-blinded, Randomized Controlled Trial

A fracture-related infection (FRI) is a difficult to treat condition in which a bone fracture and surrounding tissues are infected. This results in impaired healing and ongoing symptoms such as pain, wound leakage and swelling, which affects patients' functioning and quality of life. Despite adequate treatment in the form of extensive surgical debridement and long-term antibiotics, it is hard to obtain infection eradication.

This pilot, non-blinded, randomized controlled trial (RCT) will assess the feasibility of a subsequent, larger RCT, in which hyperbaric oxygen therapy (HBOT) will be investigated as potential treatment modality for FRI in adjunction to standard care. HBOT induces an increased oxygen tension in the body and thereby inhibits inflammation and the growth of several bacteria. Furthermore, it stimulates bone and blood vessel formation. Therefore, HBOT might be of added value in the treatment of FRI. Data on process-related outcomes, patient-reported outcome measures, and clinical parameters are obtained during this pilot study to determine whether a subsequent study investigating the efficacy of HBOT is viable.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperbaric Oxygenation; Fracture Related Infection
• Intervention / Treatment: Drug: Hyperbaric Oxygen Therapy

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robert P Weenink, MD PhD; Phone Number: +31205669111; Email: r.p.weenink@amsterdamumc.nl

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105AZ
      • Amsterdam UMC
      • Contact: Silke D de Wolde, MD; Email: s.d.dewolde@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Confirmed or highly suspected post-traumatic FRI of the lower limb, for which surgical intervention will be conducted

Exclusion Criteria:

• Patients with a known contraindication for HBOT: untreated pneumothorax; epilepsy; middle ear or thorax surgery in the previous 12 months; inability to equalize the ears; COPD grade 4 or other severe air trapping lung disease; presence of a device that is not known to be compatible with HBOT; severe claustrophobia; pregnancy; BMI ≥ 35; obstructive sleep apnoea syndrome or obesity hypoventilation syndrome with a chronic increased PaCO2 > 6.4 kPa
• Patients with an early (i.e. diagnosed <6 weeks post initial trauma) FRI, which is treated by DAIR-procedure (Debridement, Antibiotics, Implant Retention) without soft tissue reconstruction
• Patients with an active isolation precautions protocol which is incompatible with treatment in a hyperbaric chamber (i.e. with multiple patients in the chamber at the same time)
• Inability to understand Dutch or English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperbaric oxygen therapy (HBOT) + standard care; Subjects receive 20 HBOT sessions within 30 days in addition to standard care. The first HBOT session will be conducted within 7 days after the index surgery in the context of FRI treatment.	Drug: Hyperbaric Oxygen Therapy; Each HBOT session will be conducted in accordance with the following protocol: three 20 minute blocks and one 15 minute block of 100% oxygen breathing at 2.4 ATA, split up by 5 minutes of oxygen rest (i.e. breathing air with 21% oxygen at 2.4 ATA)
No Intervention: Standard care; Subjects receive standard care, consisting of at least surgical debridement of the FRI and administration of antibiotics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects included	The total number of subjects included at the end of the inclusion period (i.e. one year after the start of the study)	1 year
Number of HBOT sessions completed by each subject in the intervention group		Within 30 days after the first HBOT session
Amount of missing data per PROM per time point		At baseline and 6 weeks, 3 months, 6 months, and 1 year after the initial surgery in the context of FRI treatment
Number of complete questionnaires per PROM per timepoint		At baseline and 6 weeks, 3 months, 6 months, and 1 year after the initial surgery in the context of FRI treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EQ-5D-5L scores	Quality of life will be assessed using the five level version of the EuroQol Five Dimensions questionnaire (EQ-5D-5L). The index value can range between below 0 and 1. A higher score indicates a better quality of life.	At baseline and 6 weeks, 3 months, 6 months, and 1 year after the initial surgery in the context of FRI treatment
EQ-VAS scores	Quality of life will be assessed using the EuroQol Visual Analogue Scale (EQ-VAS). The questionnaire score can range between 0 and 100. A higher score indicates a better outcome.	At baseline and 6 weeks, 3 months, 6 months, and 1 year after the initial surgery in the context of FRI treatment
LIMB-Q scores	The subsets function, symptoms, physiological and work of the LIMB-Q questionnaire (a PROM validated for use in lower extremity trauma) will be assessed. The questionnaire score can range between 0 and 100. A higher scores indicates a better outcome.	At baseline and 6 weeks, 3 months, 6 months, and 1 year after the initial surgery in the context of FRI treatment
Time to return to life role	A self-designed questionnaire will be used to assess the time to return to life role for each subject. Life role is defined as executing structural (daily to weekly) activities, such as labour, informal care, or volunteer work. A longer time to return to life role implicates a longer recovery period.	From the initial surgery for FRI treatment to study completion at 1 year
Number of recurrence(s) of infection	The number of recurrence(s) of infection, defined as reappearance of a confirmatory FRI criterium after completing the initial surgical and antibiotic FRI treatment, occured during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Number of repeat surgeries	The number of repeat surgeries performed in the context of FRI treatment during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Number of soft tissue reconstruction failures	The number of soft-tissue reconstructions which have failed during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Number of amputations	The number of amputations performed (in the context of FRI treatment/obtaining infection control) during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Change in CRP levels	Laboratory findings on C-reactive protein (CRP) as collected in the context of standard care during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Change in WBC counts	Laboratory findings on white blood cell (WBC) counts as collected in the context of standard care during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Change in ESR levels	Laboratory findings on the erythrocyte sedimentation rate (ESR) as collected in the context of standard care during the follow-up period will be assessed.	From the initial surgery for FRI treatment to study completion at 1 year
Number of subjects with remission of infection	The number of subjects with remission of infection, defined as absence of all confirmatory criteria and suggestive signs for FRI and no use of antibiotics since >7 days, will be assessed.	One year after the initial surgery for FRI treatment
Number of subjects with non-union		One year after the initial surgery for FRI treatment
Number of subjects with complete wound healing		One year after the initial surgery for FRI treatment

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Stichting ZiektekostenVerzekering Krijgsmacht
• Investigators: Principal Investigator: Markus W Hollmann, MD PhD PhD Professor, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Lower extremity; Hyperbaric oxygen therapy; Feasibility studies; Fracture-related infection
• Additional Relevant MeSH Terms: Therapeutics; Respiratory Therapy; Oxygen Inhalation Therapy; Hyperbaric Oxygenation
• Other Study ID Numbers: SOLDIER-2026; 2026-525871-24-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No