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

Respirology. 2018 Dec;23(12):1152-1159. doi: 10.1111/resp.13374. Epub 2018 Aug 3.

Abstract

Background and objective: Combination long-acting β2 -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/Fluticasone to indacateroL/glycopyrronium in A Symptomatic COPD patient coHort) 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 (FEV1 ) 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 FEV1 ) 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 FEV1 and FVC in COPD patients with up to one exacerbation in the previous year. No new safety signals were identified.

Trial registration: ClinicalTrials.gov NCT02516592.

Keywords: chronic obstructive pulmonary disease; fluticasone; glycopyrronium; indacaterol; salmeterol.

Publication types

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

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Aged
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Drug Combinations
  • Drug Monitoring / methods
  • Drug Substitution / methods
  • Female
  • Fluticasone-Salmeterol Drug Combination* / administration & dosage
  • Fluticasone-Salmeterol Drug Combination* / adverse effects
  • Glycopyrrolate* / administration & dosage
  • Glycopyrrolate* / adverse effects
  • Humans
  • Indans* / administration & dosage
  • Indans* / adverse effects
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / adverse effects
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinolones* / administration & dosage
  • Quinolones* / adverse effects
  • Respiratory Function Tests / methods
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Drug Combinations
  • Fluticasone-Salmeterol Drug Combination
  • Indans
  • Muscarinic Antagonists
  • Quinolones
  • indacaterol-glycopyrronium combination
  • Glycopyrrolate

Associated data

  • ClinicalTrials.gov/NCT02516592