Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial

Background: Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid (ICS) maintenance therapy. Objective: We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma. Methods: In this 48-week, double-blind, placebo-controlled, parallel-group study, 398 patients aged 12 to 17 years were randomized to receive 5 mu g (2 puffs of 2.5 mu g) or 2.5 mg (2 puffs of 1.25 eta g) of once-daily tiotropium or placebo (2 puffs) administered through the Respimat device every evening, each as add-on treatment to ICS background therapy, with or without a leukotriene receptor antagonist; long-acting beta(2)-agonist therapy was not permitted during the study. Results: Improvement in peak FEV1 within 3 hours after dosing at 24 weeks (primary end point) was statistically significant with both tiotropium doses compared with placebo: 5 mg of tiotropium, 174 mL (95% CI, 76-272 mL); 2.5 mu g of tiotropium, 134 mL (95% CI, 34-234 mL). Significant improvements in trough FEV1 at week 24 (a secondary end point) were observed with the 5-mu g dose only. Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed. Conclusions: Once-daily tiotropium significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma. Larger responses were observed with the 5-mu g tiotropium dose.