Extrafine beclomethasone/formoterol compared to fluticasone/salmeterol combination therapy in COPD

Dave Singh, Gabriele Nicolini, Eddi Bindi, Massimo Corradi, Daniele Guastalla, Jorg Kampschulte, Władysław Pierzchała, Abdullah Sayiner, Mária Szilasi, Claudio Terzano, Jørgen Vestbo, FUTURE (Foster Upgrades TherapeUtic care in REspiratory disease) study group, Dave Singh, Gabriele Nicolini, Eddi Bindi, Massimo Corradi, Daniele Guastalla, Jorg Kampschulte, Władysław Pierzchała, Abdullah Sayiner, Mária Szilasi, Claudio Terzano, Jørgen Vestbo, FUTURE (Foster Upgrades TherapeUtic care in REspiratory disease) study group

Abstract

Background: The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients.

Methods: The trial was a 12-week multicentre, randomised, double-blind, double dummy study; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 μg or FP/S 500/50 μg twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre-dose in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations.

Results: BDP/FF was equivalent to FP/S in terms of TDI score and superior in terms of FEV1 change from pre-dose (p < 0.001). There were no significant differences between treatments in secondary outcome measures, confirming overall comparability in terms of efficacy and tolerability. Moreover, a clinically relevant improvement (>4 units) in SGRQ was detected in the BDP/FF group only.

Conclusion: BDP/FF extrafine combination provides COPD patients with an equivalent improvement of dyspnoea and a faster bronchodilation in comparison to FP/S.

Trial registration: ClinicalTrials.gov: NCT01245569.

Figures

Figure 1
Figure 1
Patient flow. SF: screening failure due to ineligibility; CW: consent withdrawn; EC: development of exclusion criteria; AEs: adverse events; LF: lost to follow-up; PV: protocol violations; OR: other reasons; TF: treatment failure. For some AEs (1 in the BDP/FF group and 2 in the FP/S group) the cause of withdrawn was reported as EC, as stated in the Study Termination Form of the e-CRF.
Figure 2
Figure 2
Transition dyspnoea index (TDI) score at week 12. BDP/FF, beclomethasone dipropionate/formoterol fumarate; FP/S, fluticasone propionate/salmeterol. There were no differences (p > 0.05) between BDP/FF and FP/S. The threshold for clinical relevance only applies to the TDI total domain score.
Figure 3
Figure 3
Change in FEV1. (a) Change from pre-dose in FEV1 (L) measured at baseline; (b) Change from pre-dose in FEV1 (L) measured at week 12. FEV1, forced expiratory volume in the first second; BDP/FF, beclomethasone dipropionate/formoterol fumarate; FP/S, fluticasone propionate/salmeterol. p < 0.001 at each time point compared to baseline pre-dose for both treatments and at each visit. ***p < 0.001 between treatments.
Figure 4
Figure 4
Change in SGRQ. (a) Change from baseline in SGRQ total score; (b) Change from baseline in SGRQ total score in the ITT population with FEV1 < 50% of predicted normal value. SGRQ, St. George Respiratory Questionnaire; BDP/FF, beclomethasone dipropionate/formoterol fumarate; FP/S, fluticasone propionate/salmeterol. p > 0.05 (not significant) for differences between BDP/FF and FP/S both in the general and in the FEV1 < 50% of predicted normal value population. P values shown refer to change from baseline: ***p < 0.001, and *p = 0.01.

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