E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischemic diabetic foot ulcers |
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E.1.1.1 | Medical condition in easily understood language |
Wounds on the foot or leg of diabetic patients that also have decreased blood flow to that leg. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of the study is to confirm or refute the hypothesis that HBOT is effective as an adjunctive treatment to standard wound care for patients with an ischemic DFU to prevent major amputations and to establish the cost-effectiveness and the optimal number of sessions to obtain this effect. |
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E.2.2 | Secondary objectives of the trial |
- Cost-effectiveness and budget impact - Complete wound healing - Health-related quality of life - Pain scores - Need for additional (vascular) interventions - TcpO2 before, during and after HBOT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Type I or II diabetes 2. Meggitt-Wagner 3 or 4 lower extremity ulcer(s), present for at least 4 weeks or after a minor amputation because of a previously existing ischemic DFU. In case more than one ulcer is present, the largest will be observed as target ulcer 3. Leg ischemia, 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. Adults 6. Written informed consent |
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E.4 | Principal 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. Pregnancy 7. Insufficient proficiency of local language/English, or inability to complete the questionnaires |
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E.5 End points |
E.5.1 | Primary end point(s) |
Major amputation rate (above ankle) and (major) amputation-free survival after 12 months of follow-up |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
o Complete wound healing o Time to reach complete wound healing o Freedom from minor amputation (below ankle) o Pain score (VAS) o Health-related quality of life scores (EQ-5D-5L, SF-12, Vascuqol-6) o Costs related to HBOT and conventional therapy during follow-up period o Patients' out of pocket expenses related to disease or treatment (travel expenses etc.) o Mortality o Forefoot TcpO2 before, during and after (HBOT) treatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 months, 1 year and 3 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Multi-arm, multi-stage design |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |