Efficacy of Daflon 500 mg in venous leg ulcer healing: A double-blind, randomized, controlled versus placebo trial in 107 patients

The objective of this study was to evaluate the efficacy of Daflon(R) 500 mg (Dies)* in venous ulcers. A multicenter, double-blind, randomized, controlled versus placebo (Plac) trial was conducted, with stratification according to the size of ulcer (less than or equal to 10 cm and > 10 cm). The protocol called for a two-month treatment with Dies (one tablet = 450 mg micronized purified Diosmin) or a placebo, two tablets/day, in addition to compression therapy. Evaluations were performed every fifteen days, from D0 to D60. The primary endpoint, in accordance with Alexander House group requirements were: percentage of patients with complete ulcer healing, ie, comparison between Dies and Plac group at D60, and comparison of survival curves in each group between D0 and D60 (log rank test). Secondary endpoints included ulcer surface area assessed by computerized planimetric measurements, qualitative evaluation of ulcers, and symptoms. The patients were 105 men and women ranging in age from eighteen to eighty-five years, with standard compression stocking, who were undergoing standardized local care of ulcer and had no significant arterial disease (ankle/arm systolic pressure index > 0.8). Fifty-three patients received Dies, and 52 received Plac. The 2 groups were well matched for age (m +/- 1 SD = seventy-one +/- eleven years), gender, ulcer size, and associated disorders. Among patients with ulcer size less than or equal to 10 cm (Dios = 44, Plac = 47) a significantly larger number of patients had a complete ulcer healing at two months in the Dies group (n = 14) in comparison with the Plac group (n = 6) (32% vs 13%, P = 0.028) with a significantly shorter time duration of healing (P = 0.037). No difference was shown for the secondary criteria, except for sensation of heavy legs (P = 0.039) and a less atonic aspect of ulcer (P = 0.030) in favor of Dios. Among the 14 patients with ulcer size > 10 cm (Dios = 9, Plac = 5), subjected to a descriptive analysis only, no ulcer healed. This study showed that a two-month course of Daflon 500 mg at a daily dose of two tablets, in addition to conventional treatment, is of benefit in patients with venous ulcer less than or equal to 10 cm by accelerating complete healing.