Peripheral Vascular DiseasePhase 4DIONYSIUSNCT05804097
Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?
A Phase 4 study testing Hyperbaric oxygen in people with Peripheral Vascular Disease and Diabetic Foot Ulcer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
The goal of this multicenter, multi-national, multi-arm, multi-stage, randomized controlled trial, is to determine the added benefit of hyperbaric oxygen treatment (HBOT) in patients with diabetic foot ulcers and peripheral vascular disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Vascular Disease, Diabetic Foot Ulcer, Amputation
- What is being tested?
- Hyperbaric oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 8 Oct 2021to 1 May 2025
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type I or II diabetes
- One or more deep and clinically infected lower extremity ulcers, classified as Meggitt-Wagner class 3 or 4, Texas class 2C, 3C, 2D or 3D, or WIfI class W>1, I>1 and fI>0), present for at least 4 weeks or after a minor amputation because of a previously existing ischaemic DFU on a toe or forefoot. In case more than one ulcer is present, the largest will be observed as target ulcer
- Leg ischaemia, characterized by a highest ankle systolic blood pressure < 70 mmHg, or a toe systolic pressure < 50 mmHg or a TcpO2 < 40 mmHg
- Complete assessment of peripheral arterial lesions from the aorta to the pedal arteries with duplex ultrasonography, magnetic resonance angiography, computed tomography angiography and/or intraarterial digital subtraction angiography of the ipsilateral leg
- Patients have to be discussed in, and included after a multidisciplinary consultation.
- Adults
- Written informed consent
Who cannot join
- Chronic Obstructive Pulmonary Disease (COPD) GOLD IV
- Treatment with chemotherapy, immunosuppressive drugs or systemic corticosteroids within last 3 months, as this interferes with normal wound healing
- End-stage renal disease requiring dialysis
- Metastasized malignancy
- Left ventricular failure with ejection fraction (EF) <20% or external pacemaker
- Recent thoracic surgery or middle ear surgery
Show all 10Show fewer
- Severe epilepsy
- Uncontrollable high fever
- Pregnancy
- Insufficient proficiency of local language/English, or inability to complete the questionnaires
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this multicenter, multi-national, multi-arm, multi-stage, randomized controlled trial, is to determine the added benefit of hyperbaric oxygen treatment (HBOT) in patients with diabetic foot ulcers and peripheral vascular disease. The main question is:
- What is the difference is the major amputation rate between the study arms?
Participants will be randomized to 20, 30 or 40 sessions of HBOT or a control group.
Read the detailed description
Objective: The primary objective is to assess the (cost-) effectiveness of HBOT in addition to standard wound care and vascular surgical treatment for patients with a DFU and leg ischaemia.
Study design: An international, multi-arm multi-stage (MAMS) design is chosen to conduct an efficient randomised clinical trial. At a planned interim analysis the best performing study arm(s) will be chosen to continue.
Study population: We need up to 544 patients with a Meggitt-Wagner stage 3 or 4 DFU and proven peripheral ischaemia.
Intervention: Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will compromise 90-120 minutes of HBOT at a pressure of 2.2-2.5 ATA according to international standards.
Main study parameters/endpoints: The primary endpoint is major amputation rate after 12 months. Secondary objectives are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness of the interventions.
- Conditions
- Peripheral Vascular Disease, Diabetic Foot Ulcer, Amputation
- Being tested
- Hyperbaric oxygen
- Keywords
- Diabetic Foot Ulcer, Hyperbaric Oxygen, Peripheral Vascular Disease, HBOT, DFU, Major amputation, Diabetes, Ischemia
- Medical subject headings
- Peripheral Vascular Diseases, Diabetic Foot, Diabetes Mellitus, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbaric oxygenDrug
90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Control group |
| HBOT 20 | Experimental | Patients receiving 20 sessions of concurrent Hyperbaric oxygen treatment Receives: Drug: Hyperbaric oxygen |
| HBOT 30 | Experimental | Patients receiving 30 sessions of concurrent Hyperbaric oxygen treatment Receives: Drug: Hyperbaric oxygen |
| HBOT 40 | Experimental | Patients receiving at least 40 sessions of concurrent Hyperbaric oxygen treatment Receives: Drug: Hyperbaric oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Amputations
Major amputations, defined as below the knee or above the knee amputations
Measured: 12 months after inclusion
Secondary outcomes (9)
Amputation-free survival
Time without amputation
Measured: Complete follow-up (up to 3 years)
Health-related quality of life
Quality of life based on various questionnaires (objective)
Measured: Complete follow-up (up to 3 years)
Complete wound healing
Complete wound healing
Measured: 12 months after inclusion
Pain scores
Pain scores taken by VAS questionnaire
Measured: 12 months after inclusion
Need for additional (vascular) interventions
Vascular interventions performed during time of inclusion
Measured: Complete follow-up (up to 3 years)
Cost-effectiveness and budget impact
Costs of healthcare resources, including HBOT, related to the total number of eligible patients for HBOT per year.
QALYs, based on EQ-5D-5L
Measured: Complete follow-up (up to 3 years)
Mortality
Mortality
Measured: Complete follow-up (up to 3 years)
Patients perception of improvement
Quality of life based on various questionnaires (subjective)
Measured: Complete follow-up (up to 3 years)
TcpO2 before, during and after HBOT
Measurements of TcpO2 surrounding HBOT treatment
Measured: During intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2023
- Study start8 Oct 2021
- Primary completion1 May 2025 (estimated)
- Study completion1 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Vascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized clinical trial
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, Dirk T. Ubbink, Amsterdam UMC, location AMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05804097
- Sponsor's protocol ID
- NL72855.018.20
- Acronym
- DIONYSIUS
- Status last verified
- Nov 2024
- First submitted
- 24 Mar 2023
- Last updated
- 8 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article after deidentification (text, tables, figures and appendices).
Publications
Brouwer R, van der Peet R, Hoencamp R, Koelemay M, van Dieren S, van Hulst R, Ubbink D. DIONYSIUS trial: "Does increasing oxygen nurture your symptomatic ischaemic ulcer sufficiently?" Study protocol for an international multicentre randomised trial. BMJ Open. 2023 May 25;13(5):e063503. doi: 10.1136/bmjopen-2022-063503.
PubMed 37230523
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?
- ClinicalTrials.gov ID
- NCT05804097
- Acronym / sponsor ID
- DIONYSIUS / NL72855.018.20
- Conditions
- Peripheral Vascular Disease, Diabetic Foot Ulcer, Amputation
- Keywords
- Diabetic Foot Ulcer, Hyperbaric Oxygen, Peripheral Vascular Disease, HBOT, DFU, Major amputation, Diabetes, Ischemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 8 Oct 2021 (actual)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 May 2025 (estimated)
- First posted
- 7 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this multicenter, multi-national, multi-arm, multi-stage, randomized controlled trial, is to determine the added benefit of hyperbaric oxygen treatment (HBOT) in patients with diabetic foot ulcers and peripheral vascular disease. The main question is:
- What is the difference is the major amputation rate between the study arms?
Participants will be randomized to 20, 30 or 40 sessions of HBOT or a control group.
Detailed description
Objective: The primary objective is to assess the (cost-) effectiveness of HBOT in addition to standard wound care and vascular surgical treatment for patients with a DFU and leg ischaemia.
Study design: An international, multi-arm multi-stage (MAMS) design is chosen to conduct an efficient randomised clinical trial. At a planned interim analysis the best performing study arm(s) will be chosen to continue.
Study population: We need up to 544 patients with a Meggitt-Wagner stage 3 or 4 DFU and proven peripheral ischaemia.
Intervention: Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will compromise 90-120 minutes of HBOT at a pressure of 2.2-2.5 ATA according to international standards.
Main study parameters/endpoints: The primary endpoint is major amputation rate after 12 months. Secondary objectives are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness of the interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Control group |
| HBOT 20 | Experimental | Drug: Hyperbaric oxygenPatients receiving 20 sessions of concurrent Hyperbaric oxygen treatment |
| HBOT 30 | Experimental | Drug: Hyperbaric oxygenPatients receiving 30 sessions of concurrent Hyperbaric oxygen treatment |
| HBOT 40 | Experimental | Drug: Hyperbaric oxygenPatients receiving at least 40 sessions of concurrent Hyperbaric oxygen treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Type I or II diabetes
- One or more deep and clinically infected lower extremity ulcers, classified as Meggitt-Wagner class 3 or 4, Texas class 2C, 3C, 2D or 3D, or WIfI class W>1, I>1 and fI>0), present for at least 4 weeks or after a minor amputation because of a previously existing ischaemic DFU on a toe or forefoot. In case more than one ulcer is present, the largest will be observed as target ulcer
- Leg ischaemia, characterized by a highest ankle systolic blood pressure < 70 mmHg, or a toe systolic pressure < 50 mmHg or a TcpO2 < 40 mmHg
- Complete assessment of peripheral arterial lesions from the aorta to the pedal arteries with duplex ultrasonography, magnetic resonance angiography, computed tomography angiography and/or intraarterial digital subtraction angiography of the ipsilateral leg
- Patients have to be discussed in, and included after a multidisciplinary consultation.
Key exclusion criteria (10 listed)
- Chronic Obstructive Pulmonary Disease (COPD) GOLD IV
- Treatment with chemotherapy, immunosuppressive drugs or systemic corticosteroids within last 3 months, as this interferes with normal wound healing
- End-stage renal disease requiring dialysis
- Metastasized malignancy
- Left ventricular failure with ejection fraction (EF) <20% or external pacemaker
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbaric oxygen90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA | Drug | HBOT 20, HBOT 30, HBOT 40 |
Primary outcome
Major Amputations
Time frame: 12 months after inclusion
Major amputations, defined as below the knee or above the knee amputations
9 secondary outcomes
Amputation-free survival
Time frame: Complete follow-up (up to 3 years)
Health-related quality of life
Time frame: Complete follow-up (up to 3 years)
Complete wound healing
Time frame: 12 months after inclusion
Pain scores
Time frame: 12 months after inclusion
Need for additional (vascular) interventions
Time frame: Complete follow-up (up to 3 years)
Cost-effectiveness and budget impact
Time frame: Complete follow-up (up to 3 years)
Mortality
Time frame: Complete follow-up (up to 3 years)
Patients perception of improvement
Time frame: Complete follow-up (up to 3 years)
TcpO2 before, during and after HBOT
Time frame: During intervention period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2024.
- Derived from this study: PubMed 37230523Brouwer R, van der Peet R, Hoencamp R, Koelemay M, van Dieren S, van Hulst R, Ubbink D. DIONYSIUS trial: "Does increasing oxygen nurture your symptomatic ischaemic ulcer sufficiently?" Study protocol for an international multicentre randomised trial. BMJ Open. 2023 May 25;13(5):e063503. doi: 10.1136/bmjopen-2022-063503.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article after deidentification (text, tables, figures and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hyperbaric oxygen in people with Peripheral Vascular Disease and Diabetic Foot Ulcer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Amputations (time frame: 12 months after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05804097, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2024.