[The efficacy and safety of low-dose tiotropium bromide inhaled via Respimat® in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To compare the efficacy and safety of long-term treatment (48 weeks) with tiotropium bromide (5 µg) via Respimat(®) with placebo in patients with chronic obstructive pulmonary disease (COPD).

METHODS: A total of 338 patients were randomized in this double-blind, placebo controlled, parallel study. All patients received either tiotropium bromide or placebo. Tiotropium bromide solution 5 µg (2×2.5 µg/puff) or matching placebo was delivered via Respimat(®) at a dosage of once daily for 48 weeks. Co-primary endpoints were trough forced expiratory volume in one second (FEV(1)) and the time to first exacerbation.

RESULTS: Statistically significant improvements of both trough FEV(1) and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48 compared with those in the placebo group (P < 0.000 1). Tiotropium treatment delayed the time to first exacerbation. The time was 157 days in the tiotropium group and 85 days in the placebo group. A statistically significant difference (P = 0.002 7) in favor of tiotropium was also observed. The total numbers of exacerbation during treatment were 90 and 128 in the tiotropium and placebo groups, respectively. The Poisson regression analysis gave a mean exacerbation rate per patient year exposure of 0.67 in the tiotropium group compared to 0.98 in the placebo group with a rate ratio of 0.69 (95%CI 0.50-0.93, P = 0.016 4). A much larger improvement from baseline in St. George's respiratory questionnaire (SGRQ) total score was observed for the tiotropium group than in the placebo group (P = 0.036 7), SGRQ symptom and activity scores of patients in the tiotropium group were also superior to those of patients receiving placebo. The drugs-related adverse events in the tiotropium and placebo groups were 12 cases and 11 cases, respectively.

CONCLUSIONS: Tiotropium significantly improved lung function and quality of life, delayed the time to first exacerbation, reduced the number of exacerbation. Overall, tiotropium was well tolerated.