title: Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).
abstract: The objective of this prospective, randomized, double-blind, placebo-controlled, multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria with value of FEV1 between > or =60 and 80% of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo. The percentage of patients free from exacerbation at 6 months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56% with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with more severe baseline symptoms, ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo: 63 vs. 38% (p=0.038). In conclusion, we did not find a significant difference between long-term ambroxol therapy and placebo, in preventing exacerbations in patients with COPD. In patients with more severe respiratory symptoms at baseline, however, we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo, suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD.
authors.affiliation: Dipartimento di Medicina Interna, 1 Divisione di Medicina, University of Brescia, Spedali Civili, p.le Spedali Civili, 25100 Brescia, Italy. malerba@master.cci.unibs.it
authors.forename: Mario
authors.initials: M
authors.lastname: Malerba
authors.forename: Antonio
authors.initials: A
authors.lastname: Ponticiello
authors.forename: Alessandro
authors.initials: A
authors.lastname: Radaeli
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Grassi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000551:Ambroxol / Q000627:therapeutic use*; D004311:Double-Blind Method; D005100:Expectorants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000145:classification / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D005100:Expectorants; D000551:Ambroxol