Objective: To investigate the efficacy and safety of hyaluronic acid in the local treatment of leg ulcers of venous or mixed aetiology, compared with a neutral vehicle.
Method: A 60-day double-blind, randomised, multicentre, controlled superiority trial. The primary endpoint was the percentage wound size reduction after 45 days of treatment. Secondary endpoints included pain intensity, rate of complete ulcer healing, and aspect of the wound (percentage of necrotic, fibrinous or granulation tissue) and of the peri-ulcer skin.
Results: A total of 101 patients were randomised and analysed in the intention-to-treat (ITT) population (50 in the hyaluronic acid; 51 in the control group). Seventy-five patients were considered in the per protocol (PP) population (38 vs 37, respectively). At day 45, the percentage of ulcer surface reduction was significantly greater in the hyaluronic acid treatment group (39 ± 6%) compared with the neutral vehicle (control) group (5 ± 9%) (p=0.002). A similar result was obtained at day 15, day 30 and day 60. From day 0 to day 45, pain intensity (VA S) decreased by mean 9.8 ± 3.5mm in the hyaluronic acid group, but slightly increased by 0.8 ± 3.2mm in the control group (p=0.029). Burden of pain, as estimated by the area under the curve of daily pain (from day 0 to day 60), was significantly lower in the hyaluronic acid group (121.9 ± 20.7mm2) than in the control group (207.4 ± 32.9mm2; p=0.028). Other secondary endpoints (rate of complete healing, characteristics of the wound and peri-ulcer skin) were not significantly different between the two groups. Treatments were well tolerated and adverse events were comparable between the two groups in terms of their frequency, relationship to treatment and severity.
Conclusion: Hyaluronic acid cream was significantly more effective than the neutral vehicle in the local treatment of leg ulcers of venous or mixed aetiology, in terms of wound size reduction and reducing the burden of pain, with a good safety profile.