The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial

J Allergy Clin Immunol Pract. Jan-Feb 2016;4(1):104-13.e2. doi: 10.1016/j.jaip.2015.08.017. Epub 2015 Nov 7.

Abstract

Background: Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids (ICS).

Objective: The objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat (5 μg or 2.5 μg), compared with placebo Respimat, as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma.

Methods: A phase III, double-blind, placebo-controlled trial was conducted (NCT01316380). Adults with symptomatic asthma receiving low- to medium-dose ICS (200-400 μg budesonide or equivalent dose) and a pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥60% and ≤90% of predicted normal were randomized to 12 weeks of treatment with once-daily tiotropium Respimat 5 μg or 2.5 μg, or placebo Respimat, as add-on therapy to ICS. The primary endpoint was peak FEV1(0-3h) response.

Results: In total, 464 patients were randomized (61% female; mean age 43 years; mean baseline FEV1 78% of predicted normal). After 12 weeks, both tiotropium Respimat doses were superior to placebo (adjusted mean difference from placebo: 5 μg, 128 mL; 2.5 μg, 159 mL; both P < .001). Both doses of tiotropium Respimat were also superior to placebo with regard to the secondary endpoints of adjusted mean trough FEV1 and FEV1 area under the curve(0-3h) responses, and the other endpoints of morning and evening peak expiratory flow. Adverse events were comparable across the treatment groups.

Conclusions: Once-daily tiotropium Respimat add-on therapy to low- to medium-dose ICS in adults with symptomatic asthma is an efficacious bronchodilator, and its safety and tolerability are comparable with those of placebo Respimat.

Keywords: Anticholinergic; Asthma; Bronchodilators; Control; GINA; ICS; Mild; Respimat; Symptomatic; Tiotropium.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Adult
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Budesonide / administration & dosage*
  • Budesonide / adverse effects
  • Disease Progression
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Placebo Effect
  • Spirometry
  • Tiotropium Bromide / administration & dosage*
  • Tiotropium Bromide / adverse effects
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Drug Combinations
  • Budesonide
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01316380