Tiotropium, a new long-acting anticholinergic drug is recommended as first-line bronchodilator in the management of COPD. The aim of this study was to investigate whether addition of Formoterol, a long-acting b2-agonist produces a superior bronchodilator response when compared to Tiotropium alone in subjects with moderate-to-severe stable COPD.
23 male subjects (mean age: 59.6 ± 7.6 yrs) diagnosed with COPD and no histories of exacerbation over the previous 4 weeks, were recruited into this study. Single doses of Tiotropium (18mcg) and a combination of Tiotropium plus Formoterol [18 and 12 mcg respectively) administered through a single ihaler, were given with a pMDI plus non-static spacer on two separate study days, 4-7 days apart, in a randomized, double-blind, cross-over manner. FEV1 and FVC were measured at baseline and 5min, 15min, 30min, 60min, 2hr, 3hr, 4hr, 6hr, 8hr, 12hr and 24hr following the study drug administration with a Vitalograph Gold Standard dry bellows Spirometer.
The mean baseline FEV1 value in this study population was 40.6 ± 14.1% predicted. Tiotropium plus Formoterol produced a significantly better mean difference in area under the curve change from baseline to 24 hrs for both FEV1 (p = 0.001) and FVC (p = 0.02). Also, the mean difference in trough (24 hr) values from baseline were significantly better with the combination than Tiotropium alone [(FEV1 –289.6mL vs 185.7mL; p = 0.001)(FVC –503.5mL vs 297mL; p = 0.007). The combination showed a faster onset of action for FVC, defined as an increase of at least 150mL from baseline (5.0 mins vs 12.1 mins; p = 0.02) and tended to show a longer duration of action when compared to Tiotropium alone (FEV1: p = 0.06; FVC: p = 0.05).
In patients with moderate-to-severe COPD, addition of Formoterol to Tiotropium (in a single inhaler) produces better FEV1 and FVC responses than Tiotropium alone when measured over 24 hrs.
Combination of Tiotropium and Formoterol may produce better clinical response in patients with moderate-to-severe COPD.
Sundeep Salvi, Grant monies (from industry related sources) Cipla Ltd.