title: A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.
abstract: BACKGROUND
  Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.
  
  
  OBJECTIVE
  We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.
  
  
  METHODS
  In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy.
  
  
  RESULTS
  Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV1within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27]), and the key secondary end point, trough FEV1(5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo.
  
  
  CONCLUSIONS
  Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.
authors.affiliation: Department of Pediatrics, Children's Hospital of Colorado and the University of Colorado School of Medicine, The Breathing Institute, Aurora, Colo. Electronic address: Stanley.Szefler@childrenscolorado.org.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.affiliation: Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Kevin
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Charleston Allergy and Asthma, Charleston, SC.
authors.forename: Thomas
authors.initials: T
authors.lastname: Harper
authors.affiliation: U.O. di Pediatria, Dipartimento Sperimentale di Pediatria, Policlinico "G. Rossi," Verona, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Boner
authors.affiliation: Department of Paediatric Pulmonology, Törökbálint, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Laki
authors.affiliation: Therapeutic Area Respiratory Diseases, Boehringer Ingelheim Pharma, Ingelheim am Rhein, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Engel
authors.affiliation: Therapeutic Area Respiratory Diseases, Boehringer Ingelheim Pharma, Ingelheim am Rhein, Germany.
authors.forename: Georges
authors.initials: G
authors.lastname: El Azzi
authors.affiliation: Boehringer Ingelheim, Sydney, Australia.
authors.forename: Petra
authors.initials: P
authors.lastname: Moroni-Zentgraf
authors.affiliation: Biostatistics and Data Sciences, Boehringer Ingelheim, Bracknell, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Finnigan
authors.affiliation: Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany; Allergy Center of the Ruhr University, Bochum, Germany.
authors.forename: Eckard
authors.initials: E
authors.lastname: Hamelmann
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D015990:Placebo Effect; D012129:Respiratory Function Tests; D000069447:Tiotropium Bromide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D000069447:Tiotropium Bromide
keywords: Anticholinergic drug; FEV(1); Respimat; asthma; asthma control; children; efficacy; lung function; safety; tiotropium