title: The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial.
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.
authors.affiliation: Cardio-Thoracic and Vascular Department, Respiratory Pathophysiology, University of Pisa, Pisa, Italy. Electronic address: pierluigi.paggiaro@unipi.it.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Paggiaro
authors.affiliation: Royal Devon & Exeter Hospital, Exeter, United Kingdom.
authors.forename: David M G
authors.initials: DM
authors.lastname: Halpin
authors.affiliation: Pulmonary Department, Mainz University Hospital, Mainz, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
authors.affiliation: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Engel
authors.affiliation: Biometrics and Data Management, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Conn.
authors.forename: Valentina B
authors.initials: VB
authors.lastname: Zubek
authors.affiliation: Clinical Development, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Blahova
authors.affiliation: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Moroni-Zentgraf
authors.affiliation: Department of Pneumology, Núcleo de Pesquisa em Asma e Inflamação das Vias Aéreas (Asthma Research Centre), Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Emilio
authors.initials: E
authors.lastname: Pizzichini
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D015990:Placebo Effect; D013147:Spirometry; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D004338:Drug Combinations; D019819:Budesonide; D000069447:Tiotropium Bromide
keywords: Anticholinergic; Asthma; Bronchodilators; Control; GINA; ICS; Mild; Respimat; Symptomatic; Tiotropium