Journal Article

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

Frith, Peter A, Bremner, Peter, Chang, Catherina L, Ratnavadivel, Rajeev, Thompson, Philip J, Day, Peter, Kurstjens, Nicol, Frenzel, Christina

2015

Overview

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.

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