DIONYSIUS: Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)

Overall Status

Recruiting

CT.gov ID

NCT05804097

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other)

544

Enrollment

Location

Arms

62.8

Anticipated Duration (Months)

8.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Vascular Disease Diabetic Foot Ulcer Amputation	Drug: Hyperbaric oxygen	Phase 4

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

Study Type:

Interventional

Anticipated Enrollment :

544 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized controlled trialRandomized controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?

Actual Study Start Date :

Oct 8, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Control group
Experimental: HBOT 20 Patients receiving 20 sessions of concurrent Hyperbaric oxygen treatment	Drug: Hyperbaric oxygen 90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA
Experimental: HBOT 30 Patients receiving 30 sessions of concurrent Hyperbaric oxygen treatment	Drug: Hyperbaric oxygen 90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA
Experimental: HBOT 40 Patients receiving at least 40 sessions of concurrent Hyperbaric oxygen treatment	Drug: Hyperbaric oxygen 90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA

Outcome Measures

Primary Outcome Measures

Major Amputations [12 months after inclusion]
Major amputations, defined as below the knee or above the knee amputations

Secondary Outcome Measures

Amputation-free survival [Complete follow-up (up to 3 years)]
Time without amputation
Health-related quality of life [Complete follow-up (up to 3 years)]
Quality of life based on various questionnaires (objective)
Complete wound healing [12 months after inclusion]
Complete wound healing
Pain scores [12 months after inclusion]
Pain scores taken by VAS questionnaire
Need for additional (vascular) interventions [Complete follow-up (up to 3 years)]
Vascular interventions performed during time of inclusion
Cost-effectiveness and budget impact [Complete follow-up (up to 3 years)]
Costs of healthcare resources, including HBOT, related to the total number of eligible patients for HBOT per year. QALYs, based on EQ-5D-5L
Mortality [Complete follow-up (up to 3 years)]
Mortality
Patients perception of improvement [Complete follow-up (up to 3 years)]
Quality of life based on various questionnaires (subjective)
TcpO2 before, during and after HBOT [During intervention period]
Measurements of TcpO2 surrounding HBOT treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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
Severe epilepsy
Uncontrollable high fever
Pregnancy
Insufficient proficiency of local language/English, or inability to complete the questionnaires