Beclomethasone/formoterol in the management of COPD: a randomised controlled trial.
OBJECTIVE
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 (FEV(1)) 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 FEV(1) 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.
Calverley
P M A
PM
Pulmonary and Rehabilitation Research Group, Dept of Medicine, Clinical Sciences, University Hospital Aintree, Longmoor Lane, Liverpool, United Kingdom. pmacal@liverpool.ac.uk
Kuna
P
P
Monsó
E
E
Costantini
M
M
Petruzzelli
S
S
Sergio
F
F
Varoli
G
G
Papi
A
A
Brusasco
V
V
D000420:Albuterol / Q000627:therapeutic use*; D001507:Beclomethasone / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life
D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D001507:Beclomethasone; D000420:Albuterol; D000068759:Formoterol Fumarate