Is Nonmicronized Diosmin 600?mg as Effective as Micronized Diosmin 900?mg plus Hesperidin 100?mg on Chronic Venous Disease Symptoms? Results of a Noninferiority Study

摘要

Background. Phlebotonics have beneficial effects on some symptoms related to chronic venous disease (CVD) of the lower limbs. The most commonly used one is diosmin, available in a pure semisynthetic form or as a micronized purified flavonoid fraction. Patients and Methods. The primary objective of this single-blind, randomized, parallel-group, prospective study was to assess the clinical noninferiority of nonmicronized diosmin 600?mg once daily (D-group) compared to micronized diosmin 900?mg plus hesperidin 100?mg once daily (D/H-group) over a 6-month treatment period. Adult patients with a symptomatic CVD of the lower limbs (C0-C3 grade; 20-60?mm on a 100?mm visual analog scale (VAS)) were included. The primary endpoint was the change (from baseline to last postbaseline value) of the intensity of the lower-limb symptoms on VAS. Results. 114 patients (mean age, 44.4 years; women, 90.4%) were randomized in the per-protocol analysis (D-group, n=57; D/H-group, n=57). Symptoms significantly improved in both groups with adjusted mean VAS changes of -24.9?mm (p0.0001) in the D-group and -22.8?mm (p0.0001) in the D/H-group, corresponding to approximately 50% reduction in basal symptom intensity. The difference between groups was -2.1?mm with an upper limit of one-sided 90% confidence interval equal to 1.0?mm for a noninferiority margin set at 20?mm (noninferiority demonstrated). Intent-to-treat analysis confirmed per-protocol analysis. Difficulty in swallowing the tablets (VAS) was significantly lower in the D-group compared to the D/H-group (9.4?mm and 54.7?mm at 6 months, respectively; p0.0001). The overall safety of both study drugs was good. Conclusion. Nonmicronized diosmin 600?mg was proven to have a noninferior efficacy compared to micronized diosmin 900?mg plus hesperidin 100?mg, associated with greater ease in swallowing the tablet.