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

الملخص EN

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 (p<0.0001) in the D-group and -22.8 mm (p<0.0001) 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; p<0.0001).

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.