Objective: To assess the chronobiological effect on therapeutic activi
ty of Daflon 500 mg and to determine the optimum method of administrat
ion. Design: Multicentre, randomized, double-blind, controlled trial.
Setting: Hospital outpatient clinics for vascular diseases in Hungary.
Patients: Three hundred and twenty ambulatory patients with symptoms
of chronic venous insufficiency randomized to three groups. Interventi
ons: Oral administration daily of 1000 mg of Daflon 500 mg for 2 month
s in three different ways (morning or evening or morning and evening).
Main outcome measures: Symptoms and clinical signs of chronic venous
insufficiency. Results: In each group, a statistically significant imp
rove ment was observed between the first (DO) and the last visit (D60)
concerning all symptoms. Oedema disappeared in a mean percentage of p
atients ranging between 26% and 43%, according to the group and the si
de affected (p <0.001). For the most affected leg, a significant decre
ase (p <0.001) of ankle and calf circumferences was observed in each g
roup. The first significant improvement, in comparison to D0, occurred
between D15 and D30 for all symptoms and ankle circumference. The com
parison between the groups did not disclose any difference concerning
the improvement of symptoms and signs. Conclusion: In this study, Dafl
on 500 mg demonstrated its therapeutic activity in chronic venous insu
fficiency, irrespective of the daily drug administration schedule.