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

NCT07489274 — Phase 4, Recruiting, 1480 participants, Ole Hyldegaard

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

Registry	NCT07489274, acronym HOT-NSTI
Status	Recruiting
Phase	Phase 4
Study type	Interventional; randomized, parallel, masking: none, treatment
Enrollment	1480 (Estimated)
Sponsor	Ole Hyldegaard (Other); collaborators: Københavns Universitet, AZ Sint-Lucas Brugge, Ziekenhuis Oost-Limburg, University Hospital, Antwerp, Copenhagen University Hospital, Rigshospitalet, Oslo University Hospital, Haukeland University Hospital, Turku University Hospital, Karolinska University Hospital
Conditions	Necrotizing Soft Tissue Infection
Interventions	Hyperbaric oxygen treatment, Standard of Care (Investigator Choice) (Drug, other)
Dates	start 2026-04-04, primary completion 2033-04-30 (estimated), completion 2033-06-30 (estimated), first posted 2026-03-24, last updated 2026-09-04
Locations	2 sites in Belgium, Norway

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
Standard of care	Active comparator	Other: Standard of Care (Investigator Choice)	standard of care (e.g. intensive care, surgery, antibiotics)
Standard of care + hyperbaric oxygen treatment	Experimental	Drug: Hyperbaric oxygen treatment; Other: Standard of Care (Investigator Choice)	standard of care (e.g. intensive care, surgery, antibiotics) + hyperbaric oxygen treatment

Hyperbaric oxygen treatment (Drug): 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.
Standard of Care (Investigator Choice) (Other): Standard of care (e.g. intensive care, surgery, antibiotics)

+Outcome measures

Primary outcomes

Mortality [30-day post-randomization]: 30-day all-cause mortality post-randomization

Secondary outcomes

Mortality [90-day post-randomization]: 90-day all-cause mortality post-randomization
Amputations [7 days post-randomization]: Amputation (y/n) within 7 days post-randomization

Other outcomes

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

+Eligibility

Sex: All, ages: 18 Years to any

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

+Locations (2)

Facility	City	Country	Status
University Hospital Antwerpen	Antwerp, Edegem	Belgium	Recruiting
Haukeland University Hospital	Bergen	Norway	Recruiting

+Funding

NIH grants: 2025