Abstract (provisional)

Background

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat(R) (tiotropium Respimat(R)) 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 beta2-agonists. To further explore the dose-response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat(R) 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(R) 5 mug, 2.5 mug or 1.25 mug or placebo Respimat(R), 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 (FEV1) 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 beta2-agonists were not permitted during the treatment phase. The primary efficacy end point was peak FEV1 measured within 3 hours after dosing (peak FEV1(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 FEV1(0-3h) response were observed with each tiotropium Respimat(R) dose versus placebo (all P < 0.0001). The largest difference from placebo was with tiotropium Respimat(R) 5 mug (188 mL). Trough FEV1 and FEV1 area under the curve (AUC)(0-3h) responses were greater with each tiotropium Respimat(R) dose than with placebo (all P < 0.0001), and both were greatest with 5 mug. Peak forced vital capacity (FVC)(0-3h), trough FVC and FVC AUC(0-3h) responses, versus placebo, were greatest with tiotropium Respimat(R) 5 mug (P < 0.0001, P = 0.0012 and P < 0.0001, respectively). Incidence of adverse events was comparable between placebo and all tiotropium Respimat(R) groups.

Conclusions

Once-daily tiotropium Respimat(R) add-on to medium-dose ICS improves lung function in symptomatic patients with moderate asthma. Overall, improvements were largest with tiotropium Respimat(R) 5 mug.

Trial registration: ClinicalTrials.gov identifier NCT01233284.

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