Clinical trial NCT05804097: Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?
Official title: Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Peripheral Vascular Disease
Diabetic Foot Ulcer
Amputation
Keywords: Diabetic Foot Ulcer
Hyperbaric Oxygen
Peripheral Vascular Disease
HBOT
DFU
Major amputation
Diabetes
Ischemia
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2023-04-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized clinical trial
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Major Amputations
timeFrame: 12 months after inclusion
Secondary outcomes:
measure: Amputation-free survival
timeFrame: Complete follow-up (up to 3 years)
measure: Health-related quality of life
timeFrame: Complete follow-up (up to 3 years)
measure: Complete wound healing
timeFrame: 12 months after inclusion
measure: Pain scores
timeFrame: 12 months after inclusion
measure: Need for additional (vascular) interventions
timeFrame: Complete follow-up (up to 3 years)
measure: Cost-effectiveness and budget impact
timeFrame: Complete follow-up (up to 3 years)
measure: Mortality
timeFrame: Complete follow-up (up to 3 years)
measure: Patients perception of improvement
timeFrame: Complete follow-up (up to 3 years)
measure: TcpO2 before, during and after HBOT
timeFrame: During intervention period
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Hollad
Study officials:
References: