Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: A pilot study

Background: International guidelines recommend the long-acting anticholinergic, tiotropium, or long-acting beta(2)-agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting beta(2)-agonists combined with inhaled corticosteroids (ICS) ill the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium With the combination of a long-acting beta(2)-agonist and an ICS are lacking. Methods: This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 mu g once daily (it = 56) vs. the combination of salmeterol 50 mu g Plus fluticasone 250 mu g twice daily (It = 51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12 It after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12h (AUC(0-12h)) on Day 43. Results: Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current snickers. duration of COPD, FEV1, forced vital capacity (FVC) and reversibility. Mean +/- SD FEV1 was 1.31 +/- 0.471 in the tiotropium group vs. 1.46 +/- 0.531 in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 rill acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted ill comparable bronchodilation compared with salmeterol Plus fluticasone. as measured by all the spirometric parameters at the end of the 6-week study period. FEV1 AUC(0-12h) was 1.55 +/- 0.031 in the tiotropium group vs. 1.57 +/- 0.041 in the salmeterol plus fluticasone groups (p = 0.63). Trough (predose) FEV1 was 1.54 +/- 0.031 in the tiotropium group vs. 1.46 +/- 0.031 in the combination group (p = 0.07), and peak FEV1 was 1.68 +/- 0.041 vs. 1.66 +/- 0.041, respectively, (p = 0.77). FVC A UC0-12h, trough and peak were also comparable between groups at study end (p > 0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated. Conclusions: Six weeks of treatment with tiotropium resulted ill comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies. (C ) 2006 Elsevier Ltd. All rights reserved.