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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
  1. Peter A Frith1,
  2. Philip J Thompson2,
  3. Rajeev Ratnavadivel3,
  4. Catherina L Chang4,
  5. Peter Bremner5,
  6. Peter Day6,
  7. Christina Frenzel7,
  8. Nicol Kurstjens7,
  9. the Glisten Study Group
  1. 1Respiratory Clinical Research Unit, Repatriation General Hospital, Adelaide, South Australia, Australia
  2. 2The 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
  3. 3Department of Respiratory Medicine, Gosford Hospital, Gosford, New South Wales, Australia
  4. 4Department of Respiratory and Sleep Medicine, Waikato Hospital, Hamilton, New Zealand
  5. 5St John of God Hospital, Murdoch, Western Australia, Australia
  6. 6Medical Centre, Redcliffe Peninsula 7 Day Medical Centre, Brisbane, Queensland, Australia
  7. 7Clinical Development and Medical Affairs, Novartis Pharmaceuticals Australia Pty Limited, Sydney, New South Wales, Australia
  1. Correspondence to Professor Peter Frith, Respiratory Medicine, Southern Adelaide Local Health Network, Repatriation General Hospital, 216 Daws Rd, Daw Park, SA 5041, Australia; Peter.frith{at}health.sa.gov.au

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.

  • COPD Pharmacology

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