A Randomized Double-Blind Crossover study of Tiotropium Versus Combination of Tiotropium and Formoterol in patients with Chronic Obstructive Pulmonary Disease (COPD)

Aim of the present study was to evaluate acute bronchodilator efficacy single doses of dry powder formulation of tiotropium (18 mcg) and combination of tiotropium with formoterol (18 + 12 mcg) in patients with COPD. We also evaluated improvement in exercise tolerance and sensation of dyspnea before and after exercise by Borg scale of dyspnea. Total of 27 stable COPD outpatients who were enrolled in this double blind, randomized, crossover, single dose study, of whom 21 completed both the treatment periods. Results of our study showed a faster onset of action for the combination of tiotropium with formoterol than tiotropium alone. The combination also showed trend for greater bronchodilation in terms of peak responses achieved for FEV1 and IC. Both the treatments maintained sustained bronchodilation over a period of 24 hours, though combination showed higher improvements in FEV1, FVC and IC at 24 hours. We did not find significant difference in AUC (0-12 h) and (0-24 h) for FEV1, FVC and IC between the groups. Both the treatments produced increase in 6 minute walk distance and also there was considerable reduction in Borg dyspnea score in both the treatment groups before and after 6 MWT. Results of the present study suggest that tiotropium has potential to increase IC acutely and thus produce relief of dyspnea. Addition of formoterol produced further improvement in all the pulmonary functional parameters. Once a day therapy and use of a single inhaler probably may improve adherence to therapy. Thus, combination of tiotropium with formoterol should be considered in patients with moderate to severe COPD when symptom relief is inadequate with a single bronchodilator. CONCLUSIONS: 1. The trough value for FEV1 and FVC was significantly higher for the combination of tiotropium with formoterol than with tiotropium alone. 2. FEV1, FVC and IC values were suggestive of sustained bronchodilation over a period of 24 hours for both the treatment groups, though combination produced greater response. 3. The combination treatment was associated with rapid onset of action than tiotropium alone, though the difference in the time taken for onset of action was not statistically significant. 4. Mean maximal responses (peak) achieved were higher for the combination for FEV1 and IC; though peak response in FVC was greater for tiotropium than the combination, the difference was very small. 5. There was marginal increase in the distance walked during 6 MWT after both the treatments and Borg’s dyspnea score was decreased after both the treatments, although reduction was greater with the combination. Thus we conclude from our study that combination of tiotropium with formoterol elicits faster onset of action, a trend for greater bronchodilation and sustained bronchodilation for more than 24 hours compared to tiotropium alone