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 (FEV1(0-3h)) and trough FEV1, respectively, after 12 weeks of treatment.Tiotropium 5 µg provided numerical improvements in peak FEV1(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.

Conflict of interest statement

can be found alongside this article at erj.ersjournals.com

Copyright ©ERS 2017.

Figures

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 (FEV1(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 (FEF25–75%) response over 12 weeks. Full analysis set. Common baseline mean±sd 2.23±0.96 L·s−1. *: p<0.05; **: p<0.01.