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.
Pulmonary and Rehabilitation Research Group, Dept of Medicine, Clinical Sciences, University Hospital Aintree, Longmoor Lane, Liverpool, United Kingdom. pmacal@liverpool.ac.uk
P M A
PM
Calverley
P
P
Kuna
E
E
Monsó
M
M
Costantini
S
S
Petruzzelli
F
F
Sergio
G
G
Varoli
A
A
Papi
V
V
Brusasco
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