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

  • End date
    Jan 24, 2026
  • participants needed
  • sponsor
    University Hospital Inselspital, Berne
Updated on 4 October 2022
foot ulcer


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


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

Condition Diabetic Foot Ulcer
Treatment Revascularization, Standard Wound Care
Clinical Study IdentifierNCT04939038
SponsorUniversity Hospital Inselspital, Berne
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

Informed consent as documented by signature
Patients that are at least 18 years old
Patients that have at least one and no more than two diabetic foot ulcers (DFU) of ≥ 0.5 cm2 and < 5 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 will be defined as index ulcer and the corresponding extremity as index limb (in case of two equally sized ulcers the following rules will apply: If on different feet, the dominant side and if on same foot, the more peripheral one will be the index ulcer)
Patients that have non-critical LEAD, defined by a single non-invasive examination at
Ankle brachial index (ABI) ≥ 0.5 and ≤ 0.9 AND absolute ankle pressure > 50 mmHg AND toe pressure > 30 mmHg OR
ABI ≥ 1.4 AND 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
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 defined as ABI < 0.4 (or ankle pressure < 50 mmHg or toe pressure < 30 mmHg)
No option to assess for toe pressure due to any reason at baseline
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 6 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 investigational 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 days after randomization
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