title: Tiotropium Respimat® in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma.
abstract: BACKGROUND
  Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat® SoftMist™ inhaler (tiotropium Respimat®) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting β2-agonists. To further explore the dose-response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat® as add-on to ICS in symptomatic patients with moderate persistent asthma.
  
  
  METHODS
  In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotropium Respimat® 5 μg, 2.5 μg or 1.25 μg or placebo Respimat®, once daily in the evening. Each treatment was administered for 4 weeks, without washout between treatment periods. Eligibility criteria included ≥60% and ≤90% of predicted normal forced expiratory volume in 1 second (FEV1) and seven-question Asthma Control Questionnaire mean score of ≥1.5. Patients were required to continue maintenance treatment with stable medium-dose ICS for at least 4 weeks prior to and during the treatment period. Long-acting β2-agonists were not permitted during the treatment phase. The primary efficacy end point was peak FEV1 measured within 3 hours after dosing (peak FEV1(0-3h)) at the end of each 4-week period, analysed as a response (change from study baseline).
  
  
  RESULTS
  In total, 149 patients were randomised and 141 completed the study. Statistically significant improvements in peak FEV1(0-3h) response were observed with each tiotropium Respimat® dose versus placebo (all P < 0.0001). The largest difference from placebo was with tiotropium Respimat® 5 μg (188 mL). Trough FEV1 and FEV1 area under the curve (AUC)(0-3h) responses were greater with each tiotropium Respimat® dose than with placebo (all P < 0.0001), and both were greatest with 5 μg. Peak forced vital capacity (FVC)(0-3h), trough FVC and FVC AUC(0-3h) responses, versus placebo, were greatest with tiotropium Respimat® 5 μg (P < 0.0001, P = 0.0012 and P < 0.0001, respectively). Incidence of adverse events was comparable between placebo and all tiotropium Respimat® groups.
  
  
  CONCLUSIONS
  Once-daily tiotropium Respimat® add-on to medium-dose ICS improves lung function in symptomatic patients with moderate asthma. Overall, improvements were largest with tiotropium Respimat® 5 μg.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01233284.
authors.affiliation: insaf Respiratory Research Institute GmbH, Wiesbaden, Germany. k.beeh@insaf-wi.de.
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Beeh
authors.forename: Petra
authors.initials: P
authors.lastname: Moroni-Zentgraf
authors.forename: Othmar
authors.initials: O
authors.lastname: Ablinger
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hollaenderova
authors.forename: Anna
authors.initials: A
authors.lastname: Unseld
authors.forename: Michael
authors.initials: M
authors.lastname: Engel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Korn
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide