Double-blind, double-dummy, randomized, multi-centre clinical assessment of the efficacy, tolerability and dose-effect relationship of sulodexide in chronic venous insufficiency.

A multi-centre study was carried out in 476 patients with chronic venous insufficiency to compare the efficacy, tolerability and dose-effect relationship of sulodexide given orally as either capsules or as a new, enteric-coated tablet formulation. Three comparable groups of patients each with chronic venous insufficiency of thrombotic or varicose aetiology received during 60 consecutive days either sulodexide 250 LRU (= 25 mg) capsules twice daily, 50 mg sulodexide enteric-coated tablets twice daily or 100 mg sulodexide enteric-coated tablets once daily, according to a double-blind, double-dummy, randomized design. Doppler and echoduplex examinations, supine and standing peripheral venous pressure, specific symptoms and signs, peripheral haemodynamics and safety haematology and haematochemistry were monitored monthly. The results showed that peripheral venous pressure improved to a clinically relevant and statistically significant extent in all groups and symptoms and signs were rapidly and significantly relieved. These effects were dose-related, as in both cases the recovery was faster and greater with the 100 mg per day dose however administered. Both the thrombotic and varicose aetiologic sub-groups benefited from treatment to approximately the same extent. Mild to moderate gastro-intestinal adverse experiences occurred in 48 patients evenly split between groups but spontaneously disappeared within 72 hours, none leading to treatment withdrawal. No clinically relevant modifications of peripheral haemodynamics or of safety haematology and haematochemistry was observed. The haemocoagulation parameters failed to exhibit appreciable variations. While the known clinical usefulness of sulodexide 250 LRU (= 25 mg) capsules twice daily was confirmed in this trial, the enteric-coated tablets, 50 mg twice daily or 100 mg once daily, were shown to have greater efficacy and similar tolerability to the standard formulation and dose.