Clinical trial NCT04939038: Timing of Revascularization in Patients With Diabetic Foot Ulcer and Non-critical Peripheral Artery Disease
Official title: Timing of Revascularization in Patients With Diabetic Foot Ulcer and Non-critical Peripheral Artery Disease: a Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetic Foot Ulcer
Keywords: Revascularization
Lower extremity arterial disease
Non-critical peripheral artery disease
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Bern
name: Swiss National Science Foundation
First posted: 2021-06-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with cardiovascular death
timeFrame: up to 12 months
measure: Number of patients with non-fatal myocardial infarction or all-cause stroke
timeFrame: up to 12 months after randomization
measure: Number of patients with major amputation
timeFrame: up to 12 months after randomization
measure: Number of patients with Minor amputation
timeFrame: up to 12 months after randomization
measure: Number of patients with missed diabetic foot ulcer healing
timeFrame: 90 days after randomization
measure: Number of patients with delayed diabetic foot ulcer healing
timeFrame: 45 days after randomization
Secondary outcomes:
measure: Number of patients with new ulcer of the index foot
timeFrame: up to 12 months after randomization
measure: Number of patients with all clinically-driven revascularizations at the index limb
timeFrame: up to 12 months after randomization
measure: Each component of the primary outcome individually
timeFrame: up to 12 months after randomization
measure: Number of in-hospital days and costs
timeFrame: up to 12 months after randomization
measure: Change in quality of life (QoL) assessed by the Cardiff Wound Impact Schedule questionnaire
timeFrame: from baseline to 90 days and 12 months after randomization
measure: Number of patients with major amputation-free survival
timeFrame: up to 12 months after randomization
measure: Number of patients with all-cause death
timeFrame: up to 12 months after randomization
Other outcomes:
measure: Infection of the index ulcer
timeFrame: up to 12 months after randomization
measure: Severity of infection
timeFrame: up to 12 months after randomization
measure: Index diabetic foot ulcer healing time
timeFrame: up to 12 months after randomization
measure: Change in area of the index ulcer
timeFrame: Compare at baseline and on 45 days, 90 days, 180 days, and 12 months after randomization
measure: Number of patients with major adverse limb events
timeFrame: up to 12 months after randomization
measure: Number of patients with procedure related serious adverse events
timeFrame: up to 12 months after randomization
measure: Number of patients with major bleeding
timeFrame: up to 12 months after randomization
measure: Number of serious adverse events
timeFrame: up to 12 months after randomization
Locations:
city: Basel
country: Switzerland
facility: Clinic for Angiology, University of Basel
city: Bern
country: Switzerland
facility: University Clinic for Angiology, University Hospital Inselspital, Berne
city: Lucerne
country: Switzerland
facility: Angiologie, Luzerner Kantonsspital
city: Saint Gallen
country: Switzerland
facility: Clinic for Vascular Surgery, Kantonsspital St. Gallen
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Prof. Dr. med. Iris Baumgartner
role: PRINCIPAL_INVESTIGATOR
References: