title: Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Technische Universität Dresden, University Hospital Carl Gustav Carus, Department of Pediatric Pneumology and Allergology, Fetscherstraße 74, 01307 Dresden, Germany. Electronic address: christian.vogelberg@uniklinikum-dresden.de.
authors: Christian
authors: C
authors: Vogelberg
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55218 Ingelheim am Rhein, Germany.
authors: Michael
authors: M
authors: Engel
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55218 Ingelheim am Rhein, Germany.
authors: Petra
authors: P
authors: Moroni-Zentgraf
authors: Vilnius University Hospital, Santariskiu 7, Vilnius LT-08406, Lithuania.
authors: Migle
authors: M
authors: Leonaviciute-Klimantaviciene
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88400 Biberach an der Riss, Germany.
authors: Ralf
authors: R
authors: Sigmund
authors: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd, Ridgefield, CT 06877, USA.
authors: John
authors: J
authors: Downie
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88400 Biberach an der Riss, Germany.
authors: Katja
authors: K
authors: Nething
authors: Private Practice, 18th Street November 21, Rēzekne LV4601, Latvia.
authors: Viktorija
authors: V
authors: Vevere
authors: Clinical Research of the Ozarks, 601 W Nifong Blvd, Suite 2A, Columbia, MO 65203, USA.
authors: Mark
authors: M
authors: Vandewalker
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
keywords: Adolescents; Anticholinergic; Asthma; Bronchodilator; Inhaled corticosteroids; Tiotropium