Therapeutic equivalence of two dosage forms of a micronized flavonoid fraction in patients with chronic venous insufficiency

This study was designed to demonstrate the therapeutic equivalence of the conventional form (S 5682) of a micronized flavonoid fraction (one 500-mg tablet twice daily) and a new dosage form (S 5684) (one 1000-mg packet of effervescent granules for oral solution per day) in patients with organic or functional chronic venous insufficiency after 60 days of treatment, A total of 934 outpatients were involved in this multicenter, double-masked, randomized trial, with 471 patients receiving S 5682 and 463 receiving S 5684, Efficacy equivalence between S 5682 and S 5684 was demonstrated for the three main criteria selected, The 90% confidence intervals of the differences between the two groups of the per-protocol population (0.93 to 5.90 mm for intensity of functional discomfort measured on a 100-mm visual analog scale; -6.87% to 3.67% and -4.29% to 5.98% for the percentage of improved patients with respect to heaviness and leg pain, respectively) were within the clinical equivalence intervals defined a priori (-6 to +6 mm for intensity of functional discomfort and -10 to +10% for the percentage of improved patients with respect to heaviness and pain). Efficacy equivalence between the groups was confirmed using the intent-to-treat population, Although the evolution of symptoms during treatment did not differ significantly between groups (time x group interaction), the progressive decrease in functional discomfort, pain, heaviness, and nighttime cramping scores was highly significant. At the end of treatment the reductions reached about 50% for functional discomfort and heaviness, about 60% for pain, and about 70% for cramping, No relevant difference between the two dosage forms was observed in treatment acceptability.