Adjunctive Hyperbaric Oxygen Treatment for Patients With Necrotizing Soft-Tissue Infection (HOT-NSTI Trial). (HOT-NSTI)

Adjunctive Hyperbaric Oxygen Treatment for Patients With Necrotizing Soft-Tissue Infection (HOT-NSTI Trial)

Necrotizing soft-tissue infection (NSTI) is a rare, severe, fast-progressing bacterial infection within the soft tissue compartment. The NSTI mortality rate remain high and largely unaltered in the last decades. The standard of care in NSTI is multidisciplinary and includes surgery, intensive care, and broad-spectrum antibiotics. Hyperbaric oxygen (HBO2) treatment is an adjunctive treatment potentially improving survival, but is not standard of care in many centres, presumably as no evidence of its benefit from randomized clinical trial exists.

The primary objective of this trial, HOT-NSTI, is to investigate the effect of adjunctive HBO2 treatment on 30-day all-cause mortality in patients with NSTI.

Study Overview

• Status: Recruiting
• Conditions: Necrotizing Soft Tissue Infection
• Intervention / Treatment: Other: Standard of Care (Investigator Choice); Drug: Hyperbaric oxygen treatment

• Study Type: Interventional
• Enrollment (Estimated): 1480
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Edegem
    • Antwerp, Edegem, Belgium, 2650
      • Recruiting
      • University Hospital Antwerpen
      • Contact: Symen Ligthart, MD, PhD; Phone Number: +32 489521716; Email: symen.ligthart@uza.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults (age ≥18 years)
• Surgical confirmed NSTI (defined by perioperative tissue characteristics observed by the surgeon. The diagnosis is based on sign as necrotic or deliquescent soft tissue with widespread undermining of the surrounding tissue)

Exclusion Criteria:

• Contraindications for HBO2 treatment according to local protocol (e.g., undrained pneumothorax)
• Confirmed pregnancy
• Referred to palliative care
• Previously randomized into the HOT-NSTI trial
• Known objection by the patient to participate in the trial
• Allergy against study drug

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
Active Comparator: Standard of care; standard of care (e.g. intensive care, surgery, antibiotics)	Other: Standard of Care (Investigator Choice); Standard of care (e.g. intensive care, surgery, antibiotics)
Experimental: Standard of care + hyperbaric oxygen treatment; standard of care (e.g. intensive care, surgery, antibiotics) + hyperbaric oxygen treatment	Other: Standard of Care (Investigator Choice); Standard of care (e.g. intensive care, surgery, antibiotics); Drug: Hyperbaric oxygen treatment; Patients will be randomized to either standard of care or standard of care + adjunctive sessions of HBO2 treatment consisting of 60-90 minutes (according to local protocols) 2.8ATA (284 kPa (≈18 m' seawater equivalent)) 100% oxygen breathing. The first session will be performed as soon as possible after randomization at the trial site, and at least within 12 hours from randomization. A minimum of three sessions will be performed within 48 hours after randomization. If the patient is considered clinical unstable after the initial three sessions (e.g. ongoing progression of the necrotising process or requiring intravenous blood pressure support in a dosage considered not related to sedation agents) additional sessions must be administered at a rate of one per approximately 24 hours, up to a maximum of five treatments. All sessions must be completed within a total timeframe of 96 hours from randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	30-day all-cause mortality post-randomization	30-day post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	90-day all-cause mortality post-randomization	90-day post-randomization
Amputations	Amputation (y/n) within 7 days post-randomization	7 days post-randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life questionaire	Quality of life at Day 90 evaluated with the 5Q-5D-5L and WHO-DAS questionaire	90 days post-randomization
Days alive and out of hospital	Days alive and out of hospital in the 90-day period	90 days post-randomization
Ventilator-free days	Ventilator-free days within 7 days post-randomization	7 days post-randomization
Renal-replacement therapy	Need for renal-replacement therapy (y/n) within 7 days	7 days post-randomization
Safety - serious adverse events	Number of patients with one or more serious adverse events up to 24 hours after last treatment	24 hours after last treatment

Collaborators and Investigators

• Sponsor: Ole Hyldegaard
• Collaborators: Karolinska University Hospital; Turku University Hospital; Oslo University Hospital; Rigshospitalet, Denmark; Haukeland University Hospital; University Hospital, Antwerp; Ziekenhuis Oost-Limburg; AZ Sint-Lucas Brugge; Københavns Universitet

Publications and helpful links

Helpful Links

• Official trial website

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2026
• Primary Completion (Estimated): April 30, 2033
• Study Completion (Estimated): June 30, 2033

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: clinical trial; Sepsis; Hyperbaric Oxygen Therapy; Hyperbaric Oxygen Treatment; NSTI; Necrotizing soft tissue infection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: 2025-521368-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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