title: Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.
abstract: BACKGROUND
  The fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  This 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD. The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin -50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84. Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St. George's Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.
  
  
  RESULTS
  Trough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) -29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND. The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference -23 mL; 95 % CI -54 to 8 mL). The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores. The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.
  
  
  CONCLUSIONS
  UMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.
  
  
  BACKGROUND
  ClinicalTrials.gov study ID NCT02257385; GSK study no. 116961.
authors.affiliation: GSK, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA. chris.j.kalberg@gsk.com.
authors.forename: Chris
authors.initials: C
authors.lastname: Kalberg
authors.affiliation: GSK, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: O'Dell
authors.affiliation: GSK, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Galkin
authors.affiliation: Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Newlands
authors.affiliation: Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK.
authors.forename: William A
authors.initials: WA
authors.lastname: Fahy
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage / Q000627:therapeutic use*; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use*; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D007189:Indans; D018727:Muscarinic Antagonists; D015363:Quinolones; D011812:Quinuclidines; C550468:vilanterol; C510790:indacaterol; D000069447:Tiotropium Bromide