Tiotropium Respimat® in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma

BACKGROUND: Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat® SoftMist™ inhaler (tiotropium Respimat®) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting β(2)-agonists. To further explore the dose–response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat® as add-on to ICS in symptomatic patients with moderate persistent asthma. METHODS: In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotropium Respimat® 5 μg, 2.5 μg or 1.25 μg or placebo Respimat®, once daily in the evening. Each treatment was administered for 4 weeks, without washout between treatment periods. Eligibility criteria included ≥60% and ≤90% of predicted normal forced expiratory volume in 1 second (FEV(1)) and seven-question Asthma Control Questionnaire mean score of ≥1.5. Patients were required to continue maintenance treatment with stable medium-dose ICS for at least 4 weeks prior to and during the treatment period. Long-acting β(2)-agonists were not permitted during the treatment phase. The primary efficacy end point was peak FEV(1) measured within 3 hours after dosing (peak FEV(1(0-3h))) at the end of each 4-week period, analysed as a response (change from study baseline). RESULTS: In total, 149 patients were randomised and 141 completed the study. Statistically significant improvements in peak FEV(1(0-3h)) response were observed with each tiotropium Respimat® dose versus placebo (all P < 0.0001). The largest difference from placebo was with tiotropium Respimat® 5 μg (188 mL). Trough FEV(1) and FEV(1) area under the curve (AUC)((0-3h)) responses were greater with each tiotropium Respimat® dose than with placebo (all P < 0.0001), and both were greatest with 5 μg. Peak forced vital capacity (FVC)((0-3h)), trough FVC and FVC AUC((0-3h)) responses, versus placebo, were greatest with tiotropium Respimat® 5 μg (P < 0.0001, P = 0.0012 and P < 0.0001, respectively). Incidence of adverse events was comparable between placebo and all tiotropium Respimat® groups. CONCLUSIONS: Once-daily tiotropium Respimat® add-on to medium-dose ICS improves lung function in symptomatic patients with moderate asthma. Overall, improvements were largest with tiotropium Respimat® 5 μg. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01233284