Beclomethasone/formoterol in the management of COPD: A randomised controlled trial

• Published in: Respiratory medicine 2010-12, Vol.104 (12), p.1858-1868
• Main Authors: Calverley, P.M.A, Kuna, P, Monsó, E, Costantini, M, Petruzzelli, S, Sergio, F, Varoli, G, Papi, A, Brusasco, V
• Format: Article
• Language: English
• Subjects: Albuterol - therapeutic use; Asthma; Beclomethasone - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Bronchodilator Agents - therapeutic use; Chronic obstructive airways disease; Chronic obstructive pulmonary disease, asthma; Clinical trials; COPD; Double-Blind Method; Drug Combinations; Drug therapy; Ethanolamines - therapeutic use; Exacerbations; Female; Forced Expiratory Volume - physiology; Formoterol Fumarate; Humans; Inhaled corticosteroid; Long-acting β2-agonist; Lung function; Male; Medical sciences; Metered Dose Inhalers; Middle Aged; Pharmaceutical industry; Pharmacology. Drug treatments; Pneumology; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary/Respiratory; Quality of Life; Studies
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2010.09.008

Summary Objectives To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol (non-inferiority) and versus formoterol (superiority) in patients with severe stable chronic obstructive pulmonary disease (COPD). Methods A double-blind, double-dummy, randomised, active-controlled, parallel-group study. After 4 weeks run-in with ipratropium/salbutamol (40/200 μg, three times daily) patients were randomised to receive beclomethasone/formoterol (200/12 μg pressurised metered dose inhaler), budesonide/formoterol (400/12 μg dry powder inhaler) or formoterol (12 μg dry powder inhaler) twice daily for 48 weeks. Co-primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1 s (FEV1 ) and mean rate of COPD exacerbations. Results Of 718 patients randomised, 703 (232 beclomethasone/formoterol, 238 budesonide/formoterol, 233 formoterol) were in the ITT analysis. Improvement in pre-dose morning FEV1 was 0.077 L, 0.080 L and 0.026 L for beclomethasone/formoterol, budesonide/formoterol and formoterol respectively (LS mean from the ANCOVA model). Beclomethasone/formoterol was not inferior to budesonide/formoterol (95% CI of the difference −0.052, 0.048) and superior to formoterol ( p  = 0.046). The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments (beclomethasone/formoterol 0.414, budesonide/formoterol 0.423 and formoterol 0.431). Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased. Safety profiles were as expected and treatments well-tolerated. Conclusions Beclomethasone/formoterol (400/24 μg) treatment for 48 weeks improved pulmonary function, reduced symptoms compared to formoterol, was safe and well-tolerated in patients with severe stable COPD. Neither of the long-acting β2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population.