Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Authorised, recruiting
Participants planned
1,480
Countries
5
Sites
8
Necrotizing soft-tissue infection
In effort of evaluating the efficacy of HBO2 treatment as an adjunctive treatment for patients with NSTI, we have initiated and designed the HOT-NSTI trial that will become the first randomized clinical trial assessing this objective. The purpose of the HOT-NSTI trial is to investigate the effect of adjunctive hyperbar…
Key facts
- Sponsor
- Rigshospitalet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 27 Mar 2026 → ongoing
- Decision date (initial)
- 2025-07-01
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
In effort of evaluating the efficacy of HBO2 treatment as an adjunctive treatment for patients with NSTI, we have initiated and designed the HOT-NSTI trial that will become the first randomized clinical trial assessing this objective. The purpose of the HOT-NSTI trial is to investigate the effect of adjunctive hyperbaric oxygen treatment on 30-day all-cause mortality in patients with NSTI.
Conditions and MedDRA coding
Necrotizing soft-tissue infection
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- 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 6
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 30-day all-cause mortality post-randomization
Secondary endpoints 8
- 90-day all-cause mortality post-randomization
- Amputation (y/n) within 7 days post-randomization
- Quality of life at Day 90 evaluated with the 5Q-5D-5L
- Quality of life at Day 90 evaluated with the WHO-DAS questionnaire
- Days alive and out of hospital in the 90-day period
- Ventilator-free days within 7 days post-randomization
- Need for renal-replacement therapy (y/n) within 7 days
- Number of subjects with one or more serious adverse events up to 24 hours after last treatment
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD337528 · Product
- Active substance
- Oxygen
- Pharmaceutical form
- MEDICINAL GAS, CRYOGENIC
- Route of administration
- INHALATION
- Max daily dose
- 2 d day
- Max total dose
- 5 d day
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- V03AN01 — -
- Marketing authorisation
- PL15929/0009
- MA holder
- AIR LIQUIDE LTD
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Rigshospitalet
- Sponsor organisation
- Rigshospitalet
- Address
- Blegdamsvej 9
- City
- Copenhagen Oe
- Postcode
- 2100
- Country
- Denmark
Scientific contact point
- Organisation
- Rigshospitalet
- Contact name
- Ole Hyldegaard
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Ole Hyldegaard
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
Locations
5 EU/EEA countries · 8 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 125 | 3 |
| Denmark | Authorised, recruitment pending | 525 | 1 |
| Finland | Authorised, recruitment pending | 80 | 1 |
| Norway | Authorised, recruitment pending | 150 | 2 |
| Sweden | Authorised, recruitment pending | 100 | 1 |
| Rest of world
Canada, Australia
|
— | 500 | — |
Investigational sites
AZ Sint-Jan Brugge-Oostende AV
Department of Intensive Care, Ruddershove 10, Belgium
Ziekenhuis Oost-Limburg
Department of Critical Care, Ziekenhuis Oost-Limburg, Synaps Park 1, Genk
University Hospital Antwerp
Department of Intensive Care, Drie Eikenstraat 655, 2650, Edegem
Rigshospitalet
Department of Anaesthesia, Hyperbaric Unit, Blegdamsvej 9, 2100, Copenhagen Oe
Turku University Hospital
Perioperative Services, Intensive Care Medicine and Pain Management, Kiinamyllynkatu 4-8, 20520, Turku
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2026-03-27 | 2026-04-03 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 64 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Appendix_HOT-NSTI_2025-521368-37- | 1 |
| Protocol (for publication) | D1_Protocol_HOT-NSTI_CLEAN_2025-521368-37- | 2.7 |
| Protocol (for publication) | D1_Protocol_HOT-NSTI_TrackChanges_2025-521368-37- | 2.7 |
| Protocol (for publication) | D4_EQ-5D-5L_DK | 1 |
| Protocol (for publication) | D4_EQ-5D-5L_English_BE | 1 |
| Protocol (for publication) | D4_EQ-5D-5L_FI | 1 |
| Protocol (for publication) | D4_EQ-5D-5L_Flemish_BE | 1 |
| Protocol (for publication) | D4_EQ-5D-5L_French_BE | 1 |
| Protocol (for publication) | D4_EQ-5D-5L_NO | 1 |
| Protocol (for publication) | D4_EQ-5D-5L_SE | 1 |
| Protocol (for publication) | D4_WHODAS_36_DK | 1 |
| Protocol (for publication) | D4_WHODAS_36_English_BE | 1 |
| Protocol (for publication) | D4_WHODAS_36_FI | 1 |
| Protocol (for publication) | D4_WHODAS_36_Flemish_BE | 1 |
| Protocol (for publication) | D4_WHODAS_36_French_BE | 1 |
| Protocol (for publication) | D4_WHODAS_36_NO | 1 |
| Protocol (for publication) | D4_WHODAS_36_SE | 1 |
| Recruitment arrangements (for publication) | K1_forfarande-for-rekrytering-och-samtyckesprocess - recruitment arragements_SE | R2 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_Antwerp_BE | 1 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_Brugge_BE | 1 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_DK | 1 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_en_Turku_Finnish_V4 clean | 4 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_en_Turku_Finnish_V4 edited | 4 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_Genk_BE | 1 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_NORWAY_with_trackchanges | 1 |
| Recruitment arrangements (for publication) | K1_informedconsent_patientrecruitmentprocedure_NORWAY_without_trackchanges | 1 |
| Subject information and informed consent form (for publication) | L1_Deltagerinformation_dansk_HOT-NSTI_DK | 1.1 |
| Subject information and informed consent form (for publication) | L1_Deltagerinformation_dansk_HOT-NSTI_DK_TRACKCHANGES | 1.1 |
| Subject information and informed consent form (for publication) | L1_Dine rettigheder som forsgsperson i forsg med medicin_DK | 1 |
| Subject information and informed consent form (for publication) | L1_Dutch_Participant_Information_BE | 1 |
| Subject information and informed consent form (for publication) | L1_Dutch_Relative_Information_BE | 1 |
| Subject information and informed consent form (for publication) | L1_HOT-NSTI Anhoriginformation Muntlig_SE | 3 |
| Subject information and informed consent form (for publication) | L1_HOT-NSTI Anhoriginformation_SE | 3 |
| Subject information and informed consent form (for publication) | L1_HOT-NSTI Forskningspersonsinformation_SE | 3 |
| Subject information and informed consent form (for publication) | L1_ICF HOT-NSTI_BE | 2 |
| Subject information and informed consent form (for publication) | L1_ICF HOT-NSTI_BE_ENGLISH | 1 |
| Subject information and informed consent form (for publication) | L1_ICF HOT-NSTI_BE_FRENCH | 1 |
| Subject information and informed consent form (for publication) | L1_LetterOfConsent_Patient_TEMPLATE_NL_BE | 1 |
| Subject information and informed consent form (for publication) | L1_LetterOfConsent_Relative_TEMPLATE_NL_BE | 1 |
| Subject information and informed consent form (for publication) | L1_Meddelande anhoriga HOT-NSTI svenska_FI_CLEAN | 2 |
| Subject information and informed consent form (for publication) | L1_Meddelande anhoriga HOT-NSTI svenska_FI_TRACKCHANGES | 2 |
| Subject information and informed consent form (for publication) | L1_Norwegian information to next of kind HOT NSTI_NO | 1 |
| Subject information and informed consent form (for publication) | L1_Norwegian information to patient HOT NSTI_NO | 1 |
| Subject information and informed consent form (for publication) | L1_Omaisen suostumus_FI | 2 |
| Subject information and informed consent form (for publication) | L1_Parrendeinformation_dansk_HOT-NSTI_DK | 1.1 |
| Subject information and informed consent form (for publication) | L1_Parrendeinformation_dansk_HOT-NSTI_DK_TRACKCHANGES | 1.1 |
| Subject information and informed consent form (for publication) | L1_Patientens Samtycke HOT-NSTI svenska_FI | 2 |
| Subject information and informed consent form (for publication) | L1_Patientinformation HOT-NSTI svenska_FI | 2 |
| Subject information and informed consent form (for publication) | L1_Potilaan suostumus_FI | 2 |
| Subject information and informed consent form (for publication) | L1_Samtycke anhoriga HOT-NSTI svenska_FI | 2 |
| Subject information and informed consent form (for publication) | L1_Samtykkeerklring_PARRENDE_DANSK_HOT-NSTI_DK | 1.0 |
| Subject information and informed consent form (for publication) | L1_Samtykkeerklring_PATIENT_DANSK_HOT-NSTI_DK | 1.0 |
| Subject information and informed consent form (for publication) | L1_Tiedote omaiselle HOT-NSTI_FI_CLEAN | 2 |
| Subject information and informed consent form (for publication) | L1_Tiedote omaiselle HOT-NSTI_FI_TRACKCHANGES | 2 |
| Subject information and informed consent form (for publication) | L1_Tiedote potilaalle HOT-NSTI_FI_CLEAN | 2 |
| Subject information and informed consent form (for publication) | L1_Tiedote potilaalle HOT-NSTI_FI_TRACKCHANGES | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Oxygen | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis HOT-NSTI_FI_2025-521368-37- | 1.1 |
| Synopsis of the protocol (for publication) | D1_ProtocolSynopsis_HOT-NSTI_BE_2025-521368-37- | 1.1 |
| Synopsis of the protocol (for publication) | D1_ProtocolSynopsis_HOT-NSTI_Deutch_BE_2025-521368-37- | 1.1 |
| Synopsis of the protocol (for publication) | D1_ProtocolSynopsis_HOT-NSTI_DK_2025-521368-37- | 1.1 |
| Synopsis of the protocol (for publication) | D1_ProtocolSynopsis_HOT-NSTI_French_BE_2025-521368-37- | 1.1 |
| Synopsis of the protocol (for publication) | D1_ProtocolSynopsis_Hot-NSTI_NO_2025-521368-37- | 1.1 |
| Synopsis of the protocol (for publication) | D1_ProtocolSynopsis_HOT-NSTI_SE_2025-521368-37 | 1.1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-03-18 | Denmark | Acceptable with conditions 2025-06-30
|
2025-06-30 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-07-07 | Acceptable with conditions 2025-06-30
|
2025-07-07 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-08-12 | Denmark | Acceptable 2025-09-02
|
2025-09-02 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2026-05-22 | Acceptable 2025-09-02
|
2026-05-22 |