Diabetic Foot Ulcer
Conditions
Keywords
Revascularization, Lower extremity arterial disease, Non-critical peripheral artery disease
Brief summary
This study investigates whether, compared to standard treatment, immediate restoration of blood flow (revascularization) can reduce complications and improve diabetic foot ulcer healing.
Detailed description
Background: In approximately 80% of diabetes-related lower extremity amputations, patients suffer from a foot ulcer, often caused by lower extremity arterial disease. Due to lower extremity arterial disease (LEAD), diabetic patients with foot ulcers often require lower limb amputation. Achieving arterial supply (revascularization) to the ulcer is the most important factor in healing the diabetic foot ulcer and reduces the risk of amputation. The current standard of care recommends revascularization after six weeks in patients with low-grade arterial disease of the lower extremities and nonhealing foot ulcer. The aim of this study is to demonstrate that in patients with low grade arterial disease of the lower extremities and diabetic foot ulcers, immediate revascularization results in fewer cardiovascular problems and amputations, as well as improved ulcer healing, compared to the current standard of care. Study procedure: After inclusion in the study, participants will be randomized into the control arm or the active arm. In the control arm standard wound care will be performed. In the active arm, revascularization will be performed on top of standard wound care within 7 days after randomization. Post-revascularization analysis on ankle- and toe pressure, laboratory analysis, and wound care team assessment and therapy will be performed 24 h post operation. Follow up will be on 45, 90, 180 and 365 day for patients of both arms, where ankle- and toe pressure, laboratory analysis, and wound care team assessment and therapy will be performed. Number of Participants: 240 participants in total, 120 per treatment arm Study duration: 4 years Study Centre(s): International multi-centre study with approximately 8-12 centres Participating countries: Switzerland, Germany
Interventions
PROCEDURERevascularization
Depending on the condition of the patients, patients will have either endovascular or surgical revascularization
PROCEDUREStandard wound care
Standard wound care according to guidelines
Sponsors
University of Bern
Swiss National Science Foundation
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent as documented by signature * Patients that are at least 18 years old * Patients that have at least one DFU(s) of ≥ 0.2 cm2 and ≤ 10 cm2 as assessed by the ruler method multiplying the greatest length and width of the ulcer after debridement to determine the surface area. The largest eligible ulcer (≤ 10 cm2) will be defined as index ulcer and the corresponding extremity as index limb (in case of multiple equally sized ulcers the following rules will apply: If on different feet, the dominant side and if on the same foot, the more peripheral one will be the index ulcer) * Patients that have non-critical LEAD of the index leg, defined by a single non-invasive examination at screening: * Ankle brachial index (ABI) ≥ 0.5 and ≤ 0.9 AND absolute ankle pressure ≥ 50 mmHg OR * ABI \> 0.9 OR incompressible ankle pressures AND toe brachial index (TBI) ≤ 0.7 AND absolute toe pressure ≥ 30 mmHg * Patients on medical treatment for glycemic control with diagnosis of diabetes mellitus that was assessed by criteria as recommended by the guideline 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Or patient without medical treatment but diagnosed with diabetes mellitus via HbA1c. * Patients with life expectancy \> 12 months and without any disabilities due to end-stage cancer, heart failure, severe chronic obstructive pulmonary disease (COPD), or dementia
Exclusion criteria
* Critical limb ischemia of the index leg defined as ABI ≤ 0.4 (or absolute ankle pressure \< 50 mmHg) * No option to assess for toe pressure due to any reason at baseline if ABI \> 0.9 or incompressible ankle pressures and patient inclusion is based on the toe pressure criteria. * Need for major amputation * Severe infection at the index foot according to IDSA classification * Patient refuses minor amputation despite strong recommendation due to severe infection, necrosis or osteomyelitis at screening assessment * Any revascularization procedure at the index leg within 3 months before randomization * Positive urine or blood pregnancy test result, breast feeding or intention to become pregnant * Non-compliance for any reason to procedures or study assessments (e.g. due to cognitive impairment or geographic distance) * Participation in another drug study within the 30 days preceding or during the present study * Untreated known antiphospholipid antibody syndrome and polycythaemia vera * Known significant bleeding risk, or known coagulation disorder (INR \> 3.0 and platelet count \< 30,000/mm3) without any option to correct within 7 calendar days after initial wound assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with Minor amputation | up to 12 months after randomization | — |
| Number of patients with major amputation | up to 12 months after randomization | — |
| Number of patients with non-fatal myocardial infarction or all-cause stroke | up to 12 months after randomization | — |
| Number of patients with cardiovascular death | up to 12 months | — |
| Number of patients with delayed diabetic foot ulcer healing | 45 days after randomization | Reduction of wound size of less than 50% at 45 days |
| Number of patients with missed diabetic foot ulcer healing | 90 days after randomization | i.e. Incomplete epithelization of the index ulcer at 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Each component of the primary outcome individually | up to 12 months after randomization | Primary outcome 1 to 6 |
| Number of patients with new ulcer of the index foot | up to 12 months after randomization | — |
| Number of patients with all clinically-driven revascularizations at the index limb | up to 12 months after randomization | excluding primary revascularization in the immediate re-vascularization group |
| Number of in-hospital days and costs | up to 12 months after randomization | (based on Disease-Related Group codes) as a measure of health service utilization |
| Change in quality of life (QoL) assessed by the Cardiff Wound Impact Schedule questionnaire | from baseline to 90 days and 12 months after randomization | Scores are transformed onto a scale of 0 - 100, a high score represents a 'good' QoL and a low score represent a 'poor' QoL |
| Number of patients with major amputation-free survival | up to 12 months after randomization | death of any cause or major amputation |
| Number of patients with all-cause death | up to 12 months after randomization | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Index diabetic foot ulcer healing time | up to 12 months after randomization | days after randomization |
| Severity of infection | up to 12 months after randomization | defined according to Infectious Diseases Society of America (IDSA) classification |
| Number of serious adverse events | up to 12 months after randomization | — |
| Number of patients with major bleeding | up to 12 months after randomization | as defined by Thrombolysis in Myocardial Infarction (TIMI) Score |
| Number of patients with procedure related serious adverse events | up to 12 months after randomization | — |
| Infection of the index ulcer | up to 12 months after randomization | — |
| Number of patients with major adverse limb events | up to 12 months after randomization | o Acute limb ischemia (ALI) requiring hospitalization and/ or major repeat revascularization (new bypass graft, jump/interposition graft revision, or thrombectomy / thrombolysis) |
| Change in area of the index ulcer | Compare at baseline and on 45 days, 90 days, 180 days, and 12 months after randomization | — |
Countries
Switzerland
Outcome results
None listed