Efficacy and safety of the direct switch to indacaterol/glycopyrronium from salmeterol/fluticasone in non‐frequently exacerbating COPD patients: The FLASH randomized controlled trial

ABSTRACT Background and objective Combination long‐acting β 2 ‐agonist/long‐acting muscarinic antagonist (LABA/LAMA) has demonstrated superior clinical outcomes over LABA/inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD) patients; however, data from blinded randomized controlled trials on direct switching from LABA/ICS to LABA/LAMA are lacking. FLASH (Assessment of switching salmeterol/ F luticasone to indacatero L /glycopyrronium in A S ymptomatic COPD patient co H ort) investigated if direct switch, without a washout period, from salmeterol/fluticasone (SFC) to indacaterol/glycopyrronium (IND/GLY) in COPD patients improves lung function and is well tolerated. Methods In this 12‐week, multicentre, double‐blind study, patients with moderate‐to‐severe COPD and up to one exacerbation in previous year, receiving SFC for ≥3 months, were randomized to continue SFC 50/500 μg twice daily (bd) or switch to IND/GLY 110/50 μg once daily (od). Primary endpoint was pre‐dose trough forced expiratory volume in 1 s (FEV 1 ) at Week 12. Results In total, 502 patients were randomized (1:1) to IND/GLY or SFC. Patients switched to IND/GLY demonstrated superior lung function (pre‐dose trough FEV 1 ) versus SFC at Week 12 (treatment difference (Δ) = 45 mL; P = 0.028). IND/GLY provided significant improvements in pre‐dose trough forced vital capacity (FVC; Δ = 102 mL; P = 0.002) and numerical improvements in transition dyspnoea index (TDI; Δ = 0.46; P = 0.063). Rescue medication use and COPD assessment test (CAT) scores were comparable between groups. Both treatments had similar safety profiles. Conclusion FLASH demonstrated that a direct switch to IND/GLY from SFC improved pre‐dose FEV 1 and FVC in COPD patients with up to one exacerbation in the previous year. No new safety signals were identified.