title: Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial.
abstract: BACKGROUND
  The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).
  
  
  METHODS
  This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.
  
  
  RESULTS
  773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.
  
  
  CONCLUSIONS
  GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.
  
  
  BACKGROUND
  NCT01513460.
authors.affiliation: Respiratory Clinical Research Unit, Repatriation General Hospital, Adelaide, South Australia, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Frith
authors.affiliation: The Lung Health Clinic, Centre for Asthma Allergy and Respiratory Research, University of Western Australia, and the Lung Institute of Western Australia, Perth, Western Australia, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: Department of Respiratory Medicine, Gosford Hospital, Gosford, New South Wales, Australia.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ratnavadivel
authors.affiliation: Department of Respiratory and Sleep Medicine, Waikato Hospital, Hamilton, New Zealand.
authors.forename: Catherina L
authors.initials: CL
authors.lastname: Chang
authors.affiliation: St John of God Hospital, Murdoch, Western Australia, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Bremner
authors.affiliation: Medical Centre, Redcliffe Peninsula 7 Day Medical Centre, Brisbane, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Day
authors.affiliation: Clinical Development and Medical Affairs, Novartis Pharmaceuticals Australia Pty Limited, Sydney, New South Wales, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Frenzel
authors.affiliation: Clinical Development and Medical Affairs, Novartis Pharmaceuticals Australia Pty Limited, Sydney, New South Wales, Australia.
authors.forename: Nicol
authors.initials: N
authors.lastname: Kurstjens
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D001315:Australia; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006024:Glycopyrrolate / Q000627:therapeutic use*; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide
keywords: COPD Pharmacology
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