Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial

J Allergy Clin Immunol. 2016 Aug;138(2):441-450.e8. doi: 10.1016/j.jaci.2016.01.011. Epub 2016 Mar 5.


Background: Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid (ICS) maintenance therapy.

Objective: We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma.

Methods: In this 48-week, double-blind, placebo-controlled, parallel-group study, 398 patients aged 12 to 17 years were randomized to receive 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg) of once-daily tiotropium or placebo (2 puffs) administered through the Respimat device every evening, each as add-on treatment to ICS background therapy, with or without a leukotriene receptor antagonist; long-acting β2-agonist therapy was not permitted during the study.

Results: Improvement in peak FEV1 within 3 hours after dosing at 24 weeks (primary end point) was statistically significant with both tiotropium doses compared with placebo: 5 μg of tiotropium, 174 mL (95% CI, 76-272 mL); 2.5 μg of tiotropium, 134 mL (95% CI, 34-234 mL). Significant improvements in trough FEV1 at week 24 (a secondary end point) were observed with the 5-μg dose only. Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed.

Conclusions: Once-daily tiotropium significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma. Larger responses were observed with the 5-μg tiotropium dose.

Trial registration: ClinicalTrials.gov NCT01257230.

Keywords: Adolescent; FEV(1); Respimat; anticholinergic drug; asthma; asthma control; efficacy; lung function; safety; tiotropium.

Publication types

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

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / therapeutic use
  • Area Under Curve
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Child
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Risk Factors
  • Severity of Illness Index
  • Tiotropium Bromide / administration & dosage
  • Tiotropium Bromide / adverse effects
  • Tiotropium Bromide / therapeutic use*
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01257230