title: Efficacy and safety of umeclidinium/vilanterol 62.5/25 mcg and tiotropium 18 mcg in chronic obstructive pulmonary disease: results of a 24-week, randomized, controlled trial.
abstract: BACKGROUND
  Combinations of inhaled long-acting bronchodilator therapies such as muscarinic antagonists and β2-agonists may be more effective than monotherapy in the treatment of chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  This study was a 24-week, Phase III, multicenter, randomized, blinded, double-dummy, parallel-group study of the once-daily, inhaled, fixed-dose combination of the long-acting muscarinic antagonist umeclidinium bromide and the long-acting β2-agonist vilanterol (UMEC/VI 62.5/25 mcg) versus tiotropium (TIO, 18 mcg). The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Day 169. The secondary endpoint was weighted mean FEV1 over 0–6 h post-dose at Day 168. For key endpoints, a step-down closed testing hierarchy was applied to account for multiplicity. Other efficacy and safety endpoints were assessed.
  
  
  RESULTS
  Statistically significant improvements in trough FEV1 at Day 169 (0.112 L, 95% confidence interval [CI]: 0.081, 0.144; p < 0.001) and weighted mean FEV1 over 0–6 h post-dose at Day 168 (0.105 L, 95% CI: 0.071, 0.140; p < 0.001) were observed for UMEC/VI versus TIO. In addition UMEC/VI improved health-related quality of life, and reduced requirement for the use of rescue medication compared with TIO. The incidence of adverse events was similar between treatment groups.
  
  
  CONCLUSIONS
  UMEC/VI was associated with statistically significant and clinically meaningful improvements in lung function versus TIO. UMEC/VI was well tolerated. UMEC/VI 62.5/25 mcg could provide an effective new treatment option for patients with moderate-to-very severe COPD.
authors.forename: M Reza
authors.initials: MR
authors.lastname: Maleki-Yazdi
authors.forename: Thomas
authors.initials: T
authors.lastname: Kaelin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Richard
authors.forename: Michael
authors.initials: M
authors.lastname: Zvarich
authors.forename: Alison
authors.initials: A
authors.lastname: Church
mesh_terms: D000368:Aged; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation; D011788:Quality of Life; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D011812:Quinuclidines; D012602:Scopolamine Derivatives; C550468:vilanterol; D000069447:Tiotropium Bromide