A Comparative Study of Topical Treatments for the Management of Chronic Leg Ulcers in a Multi-Center Cohort.

Background Chronic leg ulcers represent a significant clinical and economic burden due to prolonged healing times, frequent outpatient visits, and high recurrence rates. Topical wound care is widely used; however, comparative evidence supporting specific topical agents remains limited, and inappropriate or prolonged use may delay healing or increase complications. This multi-center study aimed to compare the effectiveness of three commonly used topical treatment strategies in the management of chronic leg ulcers. Methods A total of 125 patients with chronic leg ulcers of more than four weeks' duration were enrolled across multiple centers between July 1, 2025, and December 30, 2025. Two patients withdrew early and were excluded, leaving 123 patients for final analysis. Patients were allocated into three treatment groups: 22 patients received antimicrobial topical therapy, 33 patients received hyaluronic acid-based therapy, and 68 patients received a combined enzymatic topical formulation. The primary endpoint was complete ulcer healing within four months, defined as full epithelialization without discharge. Results Complete healing occurred in 45.45% of patients in the antimicrobial group, 75.76% in the hyaluronic acid group, and 94% in the combined formulation group. Mean healing time was 9.73 ± 0.09 weeks, 9.11 ± 1.02 weeks, and 5.8 ± 0.12 weeks, respectively. Logistic regression demonstrated significantly higher odds of complete healing in the hyaluronic acid group (OR 3.75, p = 0.022) and the combined formulation group (OR 4.63, p = 0.002) compared with antimicrobial therapy alone. Conclusion The choice of topical dressing significantly influences healing outcomes in patients with chronic leg ulcers. A combined enzymatic, antimicrobial, and moisture-retentive formulation was associated with faster healing and higher rates of complete ulcer closure compared with antimicrobial or hyaluronic acid therapy alone. These findings support a more individualized, evidence-based approach to topical wound care as part of comprehensive chronic leg ulcer management.