A randomized study of tiotropium Respimat^® Soft Mist^TM Inhaler vs. ipratropium pMDI in COPD

The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat® Soft MistTM Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 μg) via Respimat® SMI administered once daily, ipratropium (36 μg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1 s (FEV1) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV1 (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 μg and placebo for the primary endpoint (mean trough FEV1 response at week 12) were 0.118 and 0.149 L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 μg and ipratropium were 0.064 L (P=0.006) and 0.095 L (P<0.0001). The increases in peak FEV1, FEV1 AUC(0-6 h) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 μg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 μg daily, delivered via Respimat® SMI, significantly improved lung function compared with ipratropium pMDI and placebo. © 2007 Elsevier Ltd. All rights reserved.