search
Back to results

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

Primary Purpose

Diabetic Foot Ulcer

Status
Active
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Revascularization
Standard wound care
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Foot Ulcer focused on measuring Revascularization, Lower extremity arterial disease, Non-critical peripheral artery disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinic for Angiology, University of Basel
  • University Clinic for Angiology, University Hospital Inselspital, Berne
  • Angiologie, Luzerner Kantonsspital
  • Clinic for Vascular Surgery, Kantonsspital St. Gallen

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control Arm

Immediate revascularization

Arm Description

Standard wound care for diabetic wound ulcer

Patient will have revascularization 0 - 7 days after initial wound assessment and then receive standard wound care for diabetic wound ulcer

Outcomes

Primary Outcome Measures

Number of patients with cardiovascular death
Number of patients with non-fatal myocardial infarction or all-cause stroke
Number of patients with major amputation
Number of patients with Minor amputation
Number of patients with missed diabetic foot ulcer healing
i.e. Incomplete epithelization of the index ulcer at 90 days
Number of patients with delayed diabetic foot ulcer healing
Reduction of wound size of less than 50% at 45 days

Secondary Outcome Measures

Number of patients with new ulcer of the index foot
Number of patients with all clinically-driven revascularizations at the index limb
excluding primary revascularization in the immediate re-vascularization group
Each component of the primary outcome individually
Primary outcome 1 to 6
Number of in-hospital days and costs
(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
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
death of any cause or major amputation
Number of patients with all-cause death

Full Information

First Posted
June 23, 2021
Last Updated
October 19, 2023
Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University of Bern, Swiss National Science Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT04939038
Brief Title
Timing of Revascularization in Patients With Diabetic Foot Ulcer and Non-critical Peripheral Artery Disease
Acronym
DIFU
Official Title
Timing of Revascularization in Patients With Diabetic Foot Ulcer and Non-critical Peripheral Artery Disease: a Randomized, Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 25, 2022 (Actual)
Primary Completion Date
January 24, 2026 (Anticipated)
Study Completion Date
January 24, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University of Bern, Swiss National Science Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot Ulcer
Keywords
Revascularization, Lower extremity arterial disease, Non-critical peripheral artery disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control Arm
Arm Type
Active Comparator
Arm Description
Standard wound care for diabetic wound ulcer
Arm Title
Immediate revascularization
Arm Type
Experimental
Arm Description
Patient will have revascularization 0 - 7 days after initial wound assessment and then receive standard wound care for diabetic wound ulcer
Intervention Type
Procedure
Intervention Name(s)
Revascularization
Intervention Description
Depending on the condition of the patients, patients will have either endovascular or surgical revascularization
Intervention Type
Procedure
Intervention Name(s)
Standard wound care
Intervention Description
Standard wound care according to guidelines
Primary Outcome Measure Information:
Title
Number of patients with cardiovascular death
Time Frame
up to 12 months
Title
Number of patients with non-fatal myocardial infarction or all-cause stroke
Time Frame
up to 12 months after randomization
Title
Number of patients with major amputation
Time Frame
up to 12 months after randomization
Title
Number of patients with Minor amputation
Time Frame
up to 12 months after randomization
Title
Number of patients with missed diabetic foot ulcer healing
Description
i.e. Incomplete epithelization of the index ulcer at 90 days
Time Frame
90 days after randomization
Title
Number of patients with delayed diabetic foot ulcer healing
Description
Reduction of wound size of less than 50% at 45 days
Time Frame
45 days after randomization
Secondary Outcome Measure Information:
Title
Number of patients with new ulcer of the index foot
Time Frame
up to 12 months after randomization
Title
Number of patients with all clinically-driven revascularizations at the index limb
Description
excluding primary revascularization in the immediate re-vascularization group
Time Frame
up to 12 months after randomization
Title
Each component of the primary outcome individually
Description
Primary outcome 1 to 6
Time Frame
up to 12 months after randomization
Title
Number of in-hospital days and costs
Description
(based on Disease-Related Group codes) as a measure of health service utilization
Time Frame
up to 12 months after randomization
Title
Change in quality of life (QoL) assessed by the Cardiff Wound Impact Schedule questionnaire
Description
Scores are transformed onto a scale of 0 - 100, a high score represents a 'good' QoL and a low score represent a 'poor' QoL
Time Frame
from baseline to 90 days and 12 months after randomization
Title
Number of patients with major amputation-free survival
Description
death of any cause or major amputation
Time Frame
up to 12 months after randomization
Title
Number of patients with all-cause death
Time Frame
up to 12 months after randomization
Other Pre-specified Outcome Measures:
Title
Infection of the index ulcer
Time Frame
up to 12 months after randomization
Title
Severity of infection
Description
defined according to Infectious Diseases Society of America (IDSA) classification
Time Frame
up to 12 months after randomization
Title
Index diabetic foot ulcer healing time
Description
days after randomization
Time Frame
up to 12 months after randomization
Title
Change in area of the index ulcer
Time Frame
Compare at baseline and on 45 days, 90 days, 180 days, and 12 months after randomization
Title
Number of patients with major adverse limb events
Description
o Acute limb ischemia (ALI) requiring hospitalization and/ or major repeat revascularization (new bypass graft, jump/interposition graft revision, or thrombectomy / thrombolysis)
Time Frame
up to 12 months after randomization
Title
Number of patients with procedure related serious adverse events
Time Frame
up to 12 months after randomization
Title
Number of patients with major bleeding
Description
as defined by Thrombolysis in Myocardial Infarction (TIMI) Score
Time Frame
up to 12 months after randomization
Title
Number of serious adverse events
Time Frame
up to 12 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. Dr. med. Iris Baumgartner
Organizational Affiliation
Insel Gruppe AG, University Hospital Bern
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinic for Angiology, University of Basel
City
Basel
Country
Switzerland
Facility Name
University Clinic for Angiology, University Hospital Inselspital, Berne
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Angiologie, Luzerner Kantonsspital
City
Lucerne
Country
Switzerland
Facility Name
Clinic for Vascular Surgery, Kantonsspital St. Gallen
City
Saint Gallen
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs