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 11years were randomized to receive once-daily tiotropium 5μg (2 puffs of 2.5μg) or 2.5μg (2 puffs of 1.25μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Compared with placebo, tiotropium 5μg, but not 2.5μg, add-on therapy improved the primary end point, peak FEV1 within 3hours after dosing (5μg, 139mL [95% CI, 75-203; P<.001]; 2.5μg, 35mL [95% CI, -28 to 99; P=.27]), and the key secondary end point, trough FEV1 (5μg, 87mL [95% CI, 19-154; P=.01]; 2.5μg, 18mL [95% CI, -48 to 85; P=.59]). The safety and tolerability of tiotropium were comparable with those of placebo. Once-daily tiotropium Respimat 5μg improved lung function and was well tolerated as add-on therapy to ICSwith other maintenance therapies in children with severesymptomatic asthma.