Effect of Ozonated Gel Phonophoresis on Chronic Venous Ulcer Healing

Background and Rationale Venous leg ulcers are the most common type of chronic lower-limb wound, accounting for approximately 70% of all leg ulcers, and they arise from venous hypertension caused by valve dysfunction, venous obstruction, or impaired calf muscle pump function. Their prevalence increases with age, reaching up to 5% in individuals over 65. These ulcers are frequently recurrent and are associated with pain, reduced mobility, sleep disturbance, and diminished quality of life.

Phonophoresis uses ultrasound to enhance the transdermal delivery of topically applied agents into deeper tissue layers. Ozone, applied topically in gel form, has documented antibacterial, anti-inflammatory, antioxidant, and tissue-regenerative properties, and has shown benefit in other chronic wound applications. This study is designed to address a gap in the literature regarding the specific effect of ozonated gel delivered via phonophoresis on venous ulcer healing.

Design

This is a randomized controlled trial with four parallel groups (20 participants each):

Group A: Ozonated gel phonophoresis (ultrasound at 0.5 W/cm², 1 MHz, pulsed mode with 20% duty cycle, applied for 5-10 minutes depending on ulcer size, with ozonated gel as the coupling medium) plus conventional wound care Group B: Ultrasound therapy followed by separate topical application of ozonated gel, plus conventional wound care Group C: Ultrasound therapy alone (0.5 W/cm², 1 MHz, pulsed mode), plus conventional wound care Group D: Topical ozonated gel alone

All participants receive treatment three sessions per week for six weeks, alongside conventional medical wound care (cleansing, dressing, compression, repositioning, use of support surfaces, exercise, and medication) as applicable to their group.

Outcome Assessments

Measurements are taken at baseline (pre-treatment) and after six weeks (post-treatment):

Wound surface area and dimensions, assessed using the ImitoMeasure smartphone-based digital planimetry application Wound volume, assessed using a sterile saline-injection technique Quality of life, assessed using the Arabic version of the Wound Quality of Life (Wound-QoL) questionnaire, a 17-item tool covering body, psychological, and everyday-life subscales

Statistical Analysis Sample size (N = 80) was calculated using G*Power (version 3.1.9.2) based on wound surface area data from prior published work, to achieve 80% power at α = 0.05 with an effect size of 0.4. Descriptive statistics and one-way MANOVA will be used to compare baseline characteristics (age, weight, height, BMI) and outcome measures across groups; chi-squared testing will compare sex distribution; paired t-tests will compare pre- and post-treatment values within each group. Significance is set at p < 0.05.

Inclusion criteria

• Age range between 40 and 65 years
• Male and female patients
• Diagnosed with venous ulceration based on clinical investigation
• Venous ulcer presenting for more than 6 weeks
• Willing and able to provide informed consent
• Available for pre-treatment and post-treatment assessment

Exclusion criteria

• - Ulcer caused by conditions such as arterial disease
• Diabetes mellitus
• Active malignancy
• Psychological instability
• Skin diseases such as eczema
• Life-threatening disorders, including renal failure, myocardial infarction, and autoimmune diseases