Amputation, Diabetic Foot Ulcer, Peripheral Vascular Disease
Conditions
Keywords
Diabetic Foot Ulcer, Hyperbaric Oxygen, Peripheral Vascular Disease, HBOT, DFU, Major amputation, Diabetes, Ischemia
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.
Interventions
DRUGHyperbaric oxygen
90-120 min sessions of hyperbaric oxygen treatment of 2.2-2.5 ATA
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Amputations | 12 months after inclusion | Major amputations, defined as below the knee or above the knee amputations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Amputation-free survival | Complete follow-up (up to 3 years) | Time without amputation |
| 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 |
| 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 |
Countries
Netherlands
Outcome results
None listed