The Tiotropium Safety and Performance in Respimat® (TIOSPIR®) Trial: Spirometry Outcomes

Background: Tiotropium Safety and Performance in Respimat (R) (TIOSPIR (R)) compared the safety and efficacy of tiotropium Respimat (R) and tiotropium HandiHaler (R) in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups. Methods: TIOSPIR (R) was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial. Results: The substudy included 1370 patients who received once-daily tiotropium Respimat (R) 5 mu g (n = 461), 2.5 mu g (n = 464), or tiotropium HandiHaler (R) 18 mu g (n = 445). Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat (R) 5 mu g, 2.5 mu g, and HandiHaler (R) 18 mu g groups (difference versus HandiHaler (R) [95 % CI]: -10 [-38, 18] mL for Respimat (R) 5 mu g and, -37 [-65, -9] mL for Respimat (R) 2.5 mu g); achieving noninferiority to tiotropium HandiHaler (R) 18 mu g for tiotropium Respimat (R) 5 but not for 2.5 mu g (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat (R) 5 mu g, 2.5 mu g, and HandiHaler (R) 18 mu g groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat (R) 5-mu g, 2.5-mu g, and HandiHaler (R) 18-mu g groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not. Conclusions: The TIOSPIR (R) spirometry substudy showed that tiotropium Respimat (R) 5 mu g was noninferior to tiotropium HandiHaler (R) 18 mu g for trough FEV1, but Respimat (R) 2.5 mu g was not. Tiotropium Respimat (R) 5 mu g provides similar bronchodilator efficacy to tiotropium HandiHaler (R) 18 mu g with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction.