Effect of Photobiomodulation on Healing of Venous Leg Ulcers

Venous leg ulcers are chronic wounds associated with chronic venous disease, characterized by prolonged healing, frequent recurrence, pain, functional limitations, reduced quality of life, and substantial treatment costs. Compression therapy is the standard treatment for venous leg ulcers. Photobiomodulation may enhance tissue repair and is being investigated as an adjunct to standard wound care and compression therapy.

This is a prospective, randomized, controlled, double-blind, parallel-group clinical trial. A total of 102 participants with lower-limb venous ulcers will be randomly allocated in a 1:1 ratio to two groups. The Experimental Group (n=51) will receive active photobiomodulation combined with standard wound care and compression therapy. The Control Group (n=51) will receive sham photobiomodulation combined with the same standard wound care and compression therapy.

All ulcers will be cleansed with 0.9% saline solution at room temperature using the study site's standardized wound-care procedure. Devitalized tissue will be debrided when indicated. Hydrogel and alginate will be used as standard primary dressings, followed by sterile gauze, bandage, and adhesive tape as the secondary dressing. Participants will receive supplies and instructions to replace the primary and secondary dressings at home once daily. Compression therapy will consist of 30-mmHg compression stockings worn daily on the affected limb, removed only for bathing and sleeping. Participants will be instructed to maintain their usual nutritional intake, alternate isometric exercises with rest periods, elevate the lower limbs, and adopt healthy lifestyle habits.

Active photobiomodulation will be delivered with the e-Light IRL cluster device (DMC Equipamentos, Brazil; ANVISA registration No. 80030810174). The cluster contains eight emitters: four red emitters at 660 nm and four infrared emitters at 808 nm. Each emitter has an output power of 100 mW and delivers 6 J during a 60-second application, resulting in a total device output power of 800 mW. The applicator will be positioned perpendicular to the wound bed and applied by direct contact through a disposable transparent PVC film. The participant and treatment team will use appropriate protective eyewear.

Sham photobiomodulation will use the same device positioning and application duration, but the device will remain switched off without therapeutic light emission. Participants will wear an eye covering, and a recorded sound similar to the operating device will be reproduced to maintain participant blinding.

Participants will be treated twice weekly on Mondays and Thursdays for 16 weeks, totaling 32 active or sham sessions. Assessments will be performed at baseline and after 1, 2, and 4 months. Standardized wound photographs will be obtained before the protocol begins and after each treatment visit.

The primary outcome will be the percentage reduction in wound volume over 16 weeks. Wound volume will be estimated as wound area multiplied by wound depth. Wound area will be estimated using the modified ellipse formula (length × width × 0.785), and wound depth will be measured at the deepest point with a sterile graduated probe. Wounds with depth ≤0.1 cm will be methodologically classified as having a depth of 0 cm for volumetric analysis; for these flat wounds, the healing response will be evaluated using the percentage reduction in wound area.

Secondary outcomes will include percentage reduction in wound area, change in wound depth, complete wound healing, adverse events, wound quality assessed using the Bates-Jensen Wound Assessment Tool, pain intensity, rescue analgesic use, health-related quality of life assessed using the SF-36, clinical severity assessed using the Venous Clinical Severity Score, and direct treatment costs. Complete healing will be defined as total re-epithelialization without exudate, bleeding, or need for dressings for a continuous period of 2 weeks.

Data normality will be assessed using the Shapiro-Wilk test. Repeated continuous outcomes will be analyzed using repeated-measures analysis of variance with adjusted multiple comparisons when normally distributed, or the Friedman test with Dunn multiple comparisons and the Mann-Whitney test for between-group comparisons when non-normally distributed. Categorical outcomes will be analyzed using the chi-square test or Fisher's exact test. Time to complete healing will be analyzed using Kaplan-Meier survival curves and the log-rank test. An intention-to-treat analysis will be conducted for the main outcomes. Statistical significance will be set at p\<0.05, with 95% confidence intervals. Analyses will be performed using SPSS version 29.

• Adverse events [Срок оценки: From the first treatment session through Week 16]
• Bates-Jensen Wound Assessment Tool Score [Срок оценки: Baseline, Month 1, Month 2, and Month 4]
• Pain intensity [Срок оценки: Before and after each treatment session, twice weekly for 16 weeks]
• Health-Related Quality of Life [Срок оценки: Baseline and Month 4]
• Venous Clinical Severity Score (VCSS) [Срок оценки: Baseline, Month 1, Month 2, and Month 4]
• Wound area measurement using ImitoWound® [Срок оценки: At baseline, week 4, week 8, and week 16]
• Direct Treatment Cost [Срок оценки: Cumulative from treatment initiation through Week 16]
• Complete healing [Срок оценки: From enrollment to the end of the treatment period - Month 4]