EVALUATION OF CLINICAL EFFICACY OF A VENO TONIC DRUG - A TRIAL ON HEMISYNTHESIS DIOSMINE IN PATIENTS WITH HEAVY LEG SYNDROME

Venous-type symptoms, i.e. painful sensation of heavy, swollen or rest less legs, influenced by orthostatism and warm environment, significan tly alters quality of life of a large proportion of women. Although th e condition is frequently associated with chronic venous insufficiency , no demonstrable hemodynamic abnormality of the superficial as well a s deep venous systems of the lower limbs can be found in many patients . The pathogenesis of this syndrome remains unknown, and there is no o bjective measurement of any biological nor hemodynamic parameters that can be used for its assessment. Diosmine and other flavane derivative s have been shown beneficial in this condition using various discomfor t indexes. The aim of this work was to compare the therapeutic efficac y of two formulations of the same compound diosmine. In the analysis, particular attention was paid to the signification and usefulness of d iscomfort scales. This study was a double-blind, placebo-controlled th erapeutic trial, comparing the efficacy of a new formulation, hemisynt hesis diosmine 600 mg, one tablet per day taken in the morning, versus the usual tablet formulation of 300 mg taken twice a day (morning and evening). Treatment blindness was assured by the double placebo metho d. Two parallel groups were treated 28 days with one or the other trea tment. Randomization was performed with stratification by center. The main evaluation criteria were a composite scale of venous type symptom s (i.e. the sum of individual score 0-4 of each symptom), and a visual analog auto-evaluation scale quoted each week by the patient. The glo bal opinion of the physician on treatment adequacy to the clinical sit uation, and the degree of patient satisfaction (four grade scales) wer e used as subsidiary criteria. In order to increase the homogeneity of the study sample, inclusion was restricted to non-menopaused women ag ed 18 years and over, having given written informed consent, complaini ng of distressing sensation of heavy legs, without history of venous t hrombosis, varicose veins, superficial or deep venous reflux at the du plex-scan examination. Patients with other causes of pain in the lower limbs, taking analgesic medications or requiring elastic stocking wer e not included. 255 patients participated in the trial. Eighteen withd rew, equally distributed in both groups (6 lost. 5 interfering disease s, and two dropouts for side effects, namely headache and gastric pain ). Twenty additional patients complained of detrimental events not req uiring treatment withdrawal, equally distributed between both groups, and mainly involving digestive functions. The results confirmed a simi lar efficacy of the two drug regimens, and a small but significantly b etter improvement of the patients' auto-evaluation of their discomfort on the analogic scale (p = 0.021) for hemisynthesis diosmine 600 mg, mainly during the first two weeks; for all four criteria, the gamma ri sk showed that the once-a-day 600 mg preparation at least as effective as 300 mg twice daily (p < 0.001). On a methodological point of view, the comparison of evaluation criteria showed that the composite scale , although giving the feeling of a comprehensive and quantitative appr aisal of the discomfort in the legs, was almost equivalent to a standa rd four grade rating of heaviness, which appeared as the central sympt om of this condition. Auto-evaluation through an analogic scale proved to be more informative, more sensitive, less influenced by the physic ian's feelings and allow easier assessment of the time-course of the d rug's effects. Global evaluations by the patient and the physician did not give additional information but could be used as quality criteria , assessing the coherence of the results obtained with the scales. Thi s study demonstrated a similar efficacy of the two drug regimens, with a more rapid effectiveness of the 600 mg preparation taken once a day . Auto-evaluation on the analog scale proved to be the most informativ e and effective evaluation criteria. Also, the sensation of heavy legs were found to be the central complaint in venous type symptoms, consi stent with the denomination of ''heavy leg syndrome''.