Timing of Revascularization in Patients With Diabetic Foot Ulcer and Non-critical Peripheral Artery Disease

Diabetic Foot Ulcer Clinical Trial

— DIFU  

Official title:

Timing of Revascularization in Patients With Diabetic Foot Ulcer and Non-critical Peripheral Artery Disease: a Randomized, Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04939038
• Other study ID #: 1495 DIFU
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 25, 2022
• Est. completion date: January 24, 2026

Study information

• Verified date: October 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study investigates whether, compared to standard treatment, immediate restoration of blood flow (revascularization) can reduce complications and improve diabetic foot ulcer healing.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: January 24, 2026
• Est. primary completion date: January 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Ulcer
• Foot Ulcer
• Peripheral Arterial Disease
• Ulcer

Intervention

Procedure:
• Revascularization
Depending on the condition of the patients, patients will have either endovascular or surgical revascularization
• Standard wound care
Standard wound care according to guidelines

Locations

Country	Name	City	State
Switzerland	Clinic for Angiology, University of Basel	Basel
Switzerland	University Clinic for Angiology, University Hospital Inselspital, Berne	Bern
Switzerland	Angiologie, Luzerner Kantonsspital	Lucerne
Switzerland	Clinic for Vascular Surgery, Kantonsspital St. Gallen	Saint Gallen

Sponsors (3)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern	Swiss National Science Foundation, University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Infection of the index ulcer		up to 12 months after randomization
Other	Severity of infection	defined according to Infectious Diseases Society of America (IDSA) classification	up to 12 months after randomization
Other	Index diabetic foot ulcer healing time	days after randomization	up to 12 months after randomization
Other	Change in area of the index ulcer		Compare at baseline and on 45 days, 90 days, 180 days, and 12 months after randomization
Other	Number of patients with major adverse limb events	o Acute limb ischemia (ALI) requiring hospitalization and/ or major repeat revascularization (new bypass graft, jump/interposition graft revision, or thrombectomy / thrombolysis)	up to 12 months after randomization
Other	Number of patients with procedure related serious adverse events		up to 12 months after randomization
Other	Number of patients with major bleeding	as defined by Thrombolysis in Myocardial Infarction (TIMI) Score	up to 12 months after randomization
Other	Number of serious adverse events		up to 12 months after randomization
Primary	Number of patients with cardiovascular death		up to 12 months
Primary	Number of patients with non-fatal myocardial infarction or all-cause stroke		up to 12 months after randomization
Primary	Number of patients with major amputation		up to 12 months after randomization
Primary	Number of patients with Minor amputation		up to 12 months after randomization
Primary	Number of patients with missed diabetic foot ulcer healing	i.e. Incomplete epithelization of the index ulcer at 90 days	90 days after randomization
Primary	Number of patients with delayed diabetic foot ulcer healing	Reduction of wound size of less than 50% at 45 days	45 days after randomization
Secondary	Number of patients with new ulcer of the index foot		up to 12 months after randomization
Secondary	Number of patients with all clinically-driven revascularizations at the index limb	excluding primary revascularization in the immediate re-vascularization group	up to 12 months after randomization
Secondary	Each component of the primary outcome individually	Primary outcome 1 to 6	up to 12 months after randomization
Secondary	Number of in-hospital days and costs	(based on Disease-Related Group codes) as a measure of health service utilization	up to 12 months after randomization
Secondary	Change in quality of life (QoL) assessed by the Cardiff Wound Impact Schedule questionnaire	Scores are transformed onto a scale of 0 - 100, a high score represents a 'good' QoL and a low score represent a 'poor' QoL	from baseline to 90 days and 12 months after randomization
Secondary	Number of patients with major amputation-free survival	death of any cause or major amputation	up to 12 months after randomization
Secondary	Number of patients with all-cause death		up to 12 months after randomization