EVALUATION OF EFFICACY AND SAFETY OF ERDOSTEINE IN PATIENTS AFFECTED BY CHRONIC-BRONCHITIS DURING AN INFECTIVE EXACERBATION PHASE AND RECEIVING AMOXICILLIN AS BASIC TREATMENT (ECOBES, EUROPEAN CHRONIC OBSTRUCTIVE BRONCHITIS ERDOSTEINE STUDY)

An international multicentric study was conducted with the aim of demo nstrating that erdosteine improves the efficacy of amoxycillin in the treatment of infective exacerbation of chronic bronchitis mainly on th e clinical symptomatology (primary objective), on spirometric tests an d body temperature, without negatively influencing the tolerance (seco ndary objectives). The study was conducted as a prospective evaluation , with 2 comparative groups treated with erdosteine (300 mg x 2/day) o r placebo in association with amoxycillin (1500 mg/day) for a maximum of 10 days. The design of the trial was double-blind and parallel grou p with 2 subgroups. The treatments have been assigned randomly to a po pulation of chronic bronchitic patients in exacerbation phase of n = 2 37 subjects. The study was conducted according to to to the principles of the Declaration of Helsinki and its amendments (Hong Kong, Septemb er 1989). The primary end-point used to determine effectiveness in thi s study was the global clinical assessment (GCA) which was choosen as a general indication of activity with objective/subjective evaluation of the clinical picture. Secondary endpoints of efficacy are sputum pa rameters, functional signs of chronic obstructive bronchitis, spiromet ric tests and overall judgement of efficacy. Safety was evaluated with adverse drug reactions reporting, arterial blood pressure, heart rate and laboratory tests monitoring. The obtained values have been analyz ed with two-way and factorial ANOVA, Least Squares Catmod-SAS, Wilcoxo n and Chi-square tests. The number of patients included in the effecti veness analysis is of n = 226 subjects, due to the fact that 11 patien ts were lost due to different reasons. In term of results as far as th e primary objective of the study was concerned, erdosteine resulted mo re active than placebo. The analysis evidenced a very significative di fference for treatment, time and interaction time x treatment. No diff erence on the contrary was observed for center and the interaction cen ter x treatment. Sputum volume, body temperature and spirometric param eters were not significantly influenced by both treatments. Viscosity, appearance as well as functional signs evidenced a modification over time in favour of erdosteine. As safety is concerned the majority of a dverse events, both in the erdosteine and in the placebo group, were r elated to the gastrointestinal area. For erdosteine, of 9/17 side-effe cts, 3 were epigastralgias, 3 nauseas, 1 diarrhoea, 1 taste loss, 1 he morrhoids. For placebo of 13/17 related events 3 were epigastralgias, 4 nauseas, 4 diarrhoeas, 1 pyrosis, 1 dry mouth. In terms of severity they have been all defined as mild or moderate degree. Also from a qua litative perspective it is clear that there are no relevant difference s between the 2 treatments under evaluation, concerning safety. In con clusion of particular interest is the datum arising from the efficacy/ safety evaluation, which indicates that the clinical picture is modifi ed earlier and at deeper degree by the synergistic activity of erdoste ine and of the antibiotic without the risk of an augmentation of side- effects incidence.