A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.

Abstract

Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma. We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV₁ within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27]), and the key secondary end point, trough FEV₁ (5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo. Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.