Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study

Respir Med. 2014 Sep;108(9):1268-76. doi: 10.1016/j.rmed.2014.06.011. Epub 2014 Jul 17.

Abstract

Introduction: Tiotropium, a once-daily long-acting anticholinergic agent, has been shown to be an efficacious and safe add-on treatment for adults with symptomatic asthma, despite treatment with inhaled corticosteroids (ICS). A large proportion of asthmatic adolescents have symptomatic disease despite a wide range of therapeutic options. We investigated the efficacy and safety of three doses of tiotropium, administered in the evening (via Respimat(®) SoftMist™ inhaler), versus placebo in asthmatic adolescents symptomatic despite ICS treatment.

Methods: This randomised, double-blind, placebo-controlled, incomplete crossover study evaluated once-daily tiotropium 5 μg, 2.5 μg and 1.25 μg versus placebo in three 4-week treatment periods. Primary efficacy end point was change in peak forced expiratory volume in 1 s within 3 h post-dose from baseline (peak FEV1(0-3h)).

Results: From 139 enrolled patients, 105 were randomised to receive one of four treatment sequences. Peak FEV1(0-3h) response for tiotropium 5 μg was significantly greater versus placebo (p = 0.0043). Trough FEV1 responses were significantly greater for tiotropium 5 μg (p < 0.00001) and 1.25 μg (p = 0.0134) versus placebo, but not for 2.5 μg (p = 0.0975), while FEV1 area under the curve(0-3h) responses were significant for all doses (p = 0.00001-0.0398). Overall incidence of adverse events was balanced across treatment groups, with no dose-dependent observations. The majority of adverse events were mild to moderate in intensity.

Conclusion: This first study of tiotropium in adolescents with symptomatic asthma demonstrates that tiotropium is well tolerated and efficacious as add-on to maintenance treatment with ICS. ClinicalTrials.gov identifier; NCT01122680.

Keywords: Adolescents; Anticholinergic; Asthma; Bronchodilator; Inhaled corticosteroids; Tiotropium.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use
  • Child
  • Cholinergic Antagonists / administration & dosage*
  • Cholinergic Antagonists / adverse effects
  • Cholinergic Antagonists / therapeutic use
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume / drug effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • Male
  • Peak Expiratory Flow Rate / drug effects
  • Scopolamine Derivatives / administration & dosage*
  • Scopolamine Derivatives / adverse effects
  • Scopolamine Derivatives / therapeutic use
  • Tiotropium Bromide
  • Treatment Outcome

Substances

  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Glucocorticoids
  • Scopolamine Derivatives
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01122680