Ultrasound Assisted Wound Debridement (UAW) Versus Standard Wound Treatment in Complicated Diabetic Foot Ulcers (DFU)

June 23, 2021 updated by: Jose Luis Lazaro Martinez, Universidad Complutense de Madrid

Cellular Proliferation, Dermal Repair, and Microbiological Effectiveness of Ultrasound Assisted Wound Debridement (UAW) Versus Standard Wound Treatment in Complicated Diabetic Foot Ulcers (DFU): A Randomized Controlled Trial

The investigators aimed to elucidate the effects of UAW debridement on cellular proliferation and dermal repair in complicated diabetic foot ulcers as compared to diabetic foot ulcers receiving surgical/sharp wound debridement. A randomized controlled trial was performed involving outpatients with complicated diabetic foot ulcers that either received surgical debridement or UAW debridement every week during a six-week treatment period.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

2. Methods

2.1. Trial design

A randomized and controlled parallel clinical trial was performed involving outpatients with complicated DFU that were admitted to specialized diabetic foot unit between November 2017 to December 2019. The study protocol received full approval from the Ethics Committee of the Hospital Clínico San Carlos, Madrid, Spain (C.P. - C.I. 16/484-P). Each patient provided written informed consent before inclusion.

2.1. Intervention

Participants were randomized and assigned to receive either surgical debridement or UAW debridement every week during a six-week treatment period.

Soft tissue punch biopsies (3mm) were taken after wound debridement sessions at week zero and week six.

2.2. Follow-up Patients were followed-up for 6 months after inclusion. During the follow-up period, the investigators recorded ulcer healing. Ulcer healing was defined as complete epithelialization without any sustained drainage up to 24 weeks after the end of the study follow-up.

2.3. Sample size The sample size was calculated using the Granmo v.12 program (Municipal Institute of Medical Research, Barcelona, Spain) (https://www.imim.cat/ofertadeserveis/software-public/granmo/ ). Therefore, we analyzed 51 patients (24 in surgical group and 27 en UAW group) with an alpha of 0.05 and a statistical power of 0.80.

2.4. Randomization A computer-generated random number table was used to carry out the randomization of the patients into the two groups by an investigator who was blinded to the identity of the participants.

2.5. Blinding None of the participants, care providers, and outcome adjudicators was blinded to the interventions after assignment.

2.6. Statistical Analysis Statistical analysis was performed using SPSS for IOs version 21.0 (SPSS, Inc. Chicago, IL, USA). The assumption of normality of all continuous variables was verified using the Kolmogorov-Smirnov test. Statistical differences between groups were calculated using the Chi-Square test and, where appropriate, Fisher's exact test for categorical variables. The Mann-Whitney U test was performed for abnormally distributed quantitative parameters, and Student's t-test was performed for quantitative variables that were distributed normally. The criteria of p < 0.05 was accepted as statistically significant with a confidence interval of 95%.

This study was conducted in accordance with the Declaration of Helsinki (2013 revision) and followed all local laws and regulations in clinical research investigations in patients.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28039
        • Fancisco Javier Álvaro Afonso
      • Madrid, Spain, 28039
        • José Luis Lázaro Martínez

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • • Male and female patients ≥18 years old

    • Type 1 or type 2 diabetes with levels of HbA1c≤85.8 mmol/mol (10%) within 30 days of the beginning of the study
    • Wound stages IB, IIB, ID, and IID according to the University of Texas Diabetic Wound Classification [11]
    • Wound duration of 1-24 months
    • Wound size between 1-30 cm2 after debridement
    • Clinical picture of wounds showing mild or moderate infection, according to the criteria of the Infectious Disease Society of America Guidelines [12] and the European Wound Management Association (EWMA) [13]
    • Ankle-brachial index (ABI) ≤0.9 and ankle systolic blood pressure (ASBP) ≥70mmHg, or toe systolic blood pressure (TSBP) ≥50mmHg, ABI>0.9, TSBP ≥50mmHg and toe-brachial index (TBI) ≤0.7

Exclusion Criteria:

  • • Chronic renal disease or dialysis

    • Non-treated osteomyelitis
    • Necrotizing soft tissue infections
    • Critical limb ischaemia patients with ABI≤0.5 and ASBP<70mmHg or <50mmHg
    • Life expectancy <6 months due to malignant DFU
    • Pregnancy and lactation
    • Patients diagnosed with hepatitis or human immunodeficiency virus (HIV)
    • Patients showing local or systemic conditions that may impair tissue repair

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ultrasound Group (UAW group)
UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern.
Procedure: Ultrasound group
Every week during a six-week treatment period
Active Comparator: Surgical group

All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience.

Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus.
Procedure: Surgical group
Every week during a six-week treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline Neo-angiogenesis (Microvessel Density) at 6 Weeks
Time Frame: At week zero and week 6

Sections of tissue were immunohistochemically-stained with the CD31 marker. Light microscopy was used to count the number of microvessels/endothelial cells in a standardized grid, with the results expressed as microvessel density (Leica DMD 800 morphometric system). Microvessel density was scored according to the following scale: 0 (absent), 1 (low, at least one microvessel), 2 (moderate) and 3 (more than two micro vessels).

Higher scores mean a better outcome
At week zero and week 6
Change From Baseline Collagen Formation (Collagen Content ) at 6 Weeks
Time Frame: At week zero and week 6
Massons's trichome staining was used to differentiate collagen content from other components, such as muscle fibrin and erythrocytes, in tissue samples. Collagen content was scored according to the following scale: 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Higher scores mean a better outcome.
At week zero and week 6
Change From Baseline Myofibroblasts Formation (Myofibroblasts Content) at 6 Weeks
Time Frame: At week zero and week 6
Actin staining was used to evaluate the presence of myofibroblasts involved in wound healing. These cells increase in number during wound healing. The number of stained cells was semi-quantitatively analyzed using a 0 - 3 scaling score (0= no myofibroblasts, 1= myofibroblasts in low quantity, 2= myofibroblasts in moderate quantity, 3= myofibroblasts in high quantity)
At week zero and week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Quantitative Microbiological Analysis (Bacterial Counts Expressed Colony-forming Units Per Gram of Tissue) (CFU/g)
Time Frame: At week zero and week 6
Tissue samples were weighed and mechanically homogenised in 0.5ml volumes of sterile phosphate buffered saline (PBS, Sigma Aldrich, St Louis, MO). Homogenates were diluted and plated onto Columbia agar (BD, Sparks, MD), Columbia agar supplemented with colistin and nalidixic acid (BD), MacConkey agar (BD), and Sabouraud dextrose agar (BD) using a spiral plater workstation (Don Whitley Scientific, Shipley, UK).The limit of detection was 10 colony-forming units (CFU). Results were expressed as CFU per gram of tissue (CFU/g). Isolated microorganisms were identified by standard criteria and the BBL Crystal identification system (BD). Susceptibility testing of Staphylococcus aureus isolates for oxacillin was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines, using a 30g cefoxitin disc and Mueller-Hinton agar .
At week zero and week 6
Wound Score at 6 Weeks
Time Frame: Six weeks
Wound bed tissue was evaluated for presence, quality, and consistency of granulation tissue using a validated wound scoring system, with scores ranging between a minimum of zero points and maximum of seven points. Higher scores mean a better outcome.
Six weeks
Wound Size
Time Frame: 6 weeks
A planimetric measurements of wound size were conducted using Visitrak (Smith & Nephew, Hull, UK), with the area of the lesion determined with an approximation of ±5mm2
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Complutense de Madrid

Collaborators

Yolanda García Álvarez
Francisco Javier Álvaro Afonso
David Sevillano Fernández
Irene Sanz Corbalan
Esther García Morales

Investigators

  • Principal Investigator: Lázaro Martinez, Professor, Complutense University of Madrid

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2017

Primary Completion (Actual)

November 1, 2018

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

October 30, 2020

First Submitted That Met QC Criteria

November 17, 2020

First Posted (Actual)

November 18, 2020

Study Record Updates

Last Update Posted (Actual)

July 14, 2021

Last Update Submitted That Met QC Criteria

June 23, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C.P. - C.I. 16/484-P

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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