A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma

Abstract

We present results from the first phase III trial of once-daily tiotropium add-on to inhaled corticosteroids (ICS) plus one or more controller therapies in adolescents with severe symptomatic asthma.In this double-blind, parallel-group trial (NCT01277523), 392 patients aged 12-17 years were randomised to receive once-daily tiotropium 5 µg or 2.5 µg, or placebo, as an add-on to ICS plus other controller therapies over 12 weeks. The primary and key secondary end-points were change from baseline (response) in peak forced expiratory volume in 1 s (FEV₁) within 3 h post-dosing (FEV_1(0-3h)) and trough FEV₁, respectively, after 12 weeks of treatment.Tiotropium 5 µg provided numerical improvements in peak FEV_1(0-3h) response, compared with placebo (90 mL; p=0.104), and significant improvements were observed with tiotropium 2.5 µg (111 mL; p=0.046). Numerical improvements in trough FEV₁ response and asthma control were observed with both tiotropium doses, compared with placebo. The safety and tolerability of tiotropium were comparable with those of placebo.Once-daily tiotropium Respimat add-on to ICS plus one or more controller therapies in adolescents with severe symptomatic asthma was well tolerated. The primary end-point of efficacy was not met, although positive trends for improvements in lung function and asthma control were observed.

FIGURE 1

Study design. Usual background therapy was defined as high-dose inhaled corticosteroids (ICS) plus one or more controller therapies (e.g. a long-acting β₂-agonist or leukotriene receptor antagonist) or medium-dose ICS plus two or more controller therapies (e.g. a long-acting β₂-agonist and/or leukotriene receptor antagonist and/or sustained-release theophylline). High-dose ICS was defined as >400 µg budesonide or equivalent in patients aged 12–14 years and 800–1600 µg budesonide or equivalent in patients aged 15–17 years. Medium-dose ICS was defined as 200–400 µg budesonide or equivalent in patients aged 12–14 years and 400–800 µg budesonide or equivalent in patients aged 15–17 years [6]. ^#: two puffs of 2.5 μg; ^¶: two puffs of 1.25 μg; ⁺: two puffs.

FIGURE 2

CONSORT diagram.

FIGURE 3

Peak forced expiratory volume in 1 s within 3 h post-dosing (FEV_1(0–3h)) response over 12 weeks. Full analysis set. Common baseline mean±sd FEV₁ 2525±618 mL. Data are presented as mean±se. *: p<0.05.

FIGURE 4

Trough forced expiratory volume in 1 s (FEV₁) response over 12 weeks. Full analysis set. Common baseline mean±sd FEV₁ 2525±618 mL. Data are presented as mean±se. *: p<0.05.

FIGURE 5

Forced expiratory flow at 25–75% of forced vital capacity (FEF_25–75%) response over 12 weeks. Full analysis set. Common baseline mean±sd 2.23±0.96 L·s⁻¹. *: p<0.05; **: p<0.01.