Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?

Diabetic Foot Ulcer Clinical Trial

— DIONYSIUS  

Official title:

Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05804097
• Other study ID #: NL72855.018.20
• Status: Recruiting
• Phase: Phase 4
• Start date: October 8, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2023
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Joost R Meijering, MD
• Phone: 0031627163204
• Email: dionysius[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 544
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Type I or II diabetes

2. 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

3. Leg ischaemia, characterized by a highest ankle systolic blood pressure < 70 mmHg, or a toe systolic pressure < 50 mmHg or a TcpO2 < 40 mmHg

4. 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

5. Patients have to be discussed in, and included after a multidisciplinary consultation.

6. Adults

7. Written informed consent

Exclusion Criteria:

1. Chronic Obstructive Pulmonary Disease (COPD) GOLD IV

2. Treatment with chemotherapy, immunosuppressive drugs or systemic corticosteroids within last 3 months, as this interferes with normal wound healing

3. End-stage renal disease requiring dialysis

4. Metastasized malignancy

5. Left ventricular failure with ejection fraction (EF) <20% or external pacemaker

6. Recent thoracic surgery or middle ear surgery

7. Severe epilepsy

8. Uncontrollable high fever

9. Pregnancy

10. Insufficient proficiency of local language/English, or inability to complete the questionnaires

Related Conditions & MeSH terms

• Amputation
• Diabetic Foot
• Diabetic Foot Ulcer
• Foot Ulcer
• Peripheral Arterial Disease
• Peripheral Vascular Disease
• Peripheral Vascular Diseases
• Ulcer
• Vascular Diseases

Intervention

Drug:
• Hyperbaric oxygen
90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam	Noord-Hollad

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Amputations	Major amputations, defined as below the knee or above the knee amputations	12 months after inclusion
Secondary	Amputation-free survival	Time without amputation	Complete follow-up (up to 3 years)
Secondary	Health-related quality of life	Quality of life based on various questionnaires (objective)	Complete follow-up (up to 3 years)
Secondary	Complete wound healing	Complete wound healing	12 months after inclusion
Secondary	Pain scores	Pain scores taken by VAS questionnaire	12 months after inclusion
Secondary	Need for additional (vascular) interventions	Vascular interventions performed during time of inclusion	Complete follow-up (up to 3 years)
Secondary	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	Complete follow-up (up to 3 years)
Secondary	Mortality	Mortality	Complete follow-up (up to 3 years)
Secondary	Patients perception of improvement	Quality of life based on various questionnaires (subjective)	Complete follow-up (up to 3 years)
Secondary	TcpO2 before, during and after HBOT	Measurements of TcpO2 surrounding HBOT treatment	During intervention period