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

Thorax. 2015 Jun;70(6):519-27. doi: 10.1136/thoraxjnl-2014-206670. Epub 2015 Apr 3.

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.

Trial registration number: NCT01513460.

Keywords: COPD Pharmacology.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Androstadienes / therapeutic use*
  • Australia
  • Bronchodilator Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluticasone
  • Forced Expiratory Volume / drug effects*
  • Glycopyrrolate / therapeutic use*
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • New Zealand
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Risk Factors
  • Salmeterol Xinafoate
  • Scopolamine Derivatives / therapeutic use*
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Tiotropium Bromide
  • Treatment Outcome

Substances

  • Androstadienes
  • Bronchodilator Agents
  • Scopolamine Derivatives
  • Salmeterol Xinafoate
  • Fluticasone
  • Albuterol
  • Glycopyrrolate
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01513460