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

Universidad Complutense de Madrid51 enrolled

Overview

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.

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.

Conditions

Diabetic Foot Ulcer

Interventions

Ultrasound groupPROCEDURE

Every week during a six-week treatment period

Surgical groupPROCEDURE

Every week during a six-week treatment period

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Fancisco Javier Álvaro Afonso

Madrid, Spain

José Luis Lázaro Martínez

Madrid, Spain

Outcomes

Primary Outcomes

Change From Baseline Neo-angiogenesis (Microvessel Density) at 6 Weeks

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

Time frame: At week zero and week 6

Change From Baseline Collagen Formation (Collagen Content ) at 6 Weeks

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.

Time frame: At week zero and week 6

Change From Baseline Myofibroblasts Formation (Myofibroblasts Content) at 6 Weeks

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)

Time frame: At week zero and week 6

Secondary Outcomes

Comparison of Quantitative Microbiological Analysis (Bacterial Counts Expressed Colony-forming Units Per Gram of Tissue) (CFU/g)

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 .

Data from ClinicalTrials.gov

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