Long-term triple therapy de-escalation to indacaterol/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): a randomized, double-blind, triple-dummy clinical trial
Many patients with chronic obstructive pulmonary disease (COPD) receiving triple therapy, i.e. a long-acting beta2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) plus an inhaled corticosteroid (ICS), are not frequent exacerbators. There are no randomised controlled trials investigating ICS withdrawal in these patients.
This 26-week, randomised, double-blind, triple-dummy study in non-frequently exacerbating patients with moderate-to-severe COPD was the first to evaluate the safety and efficacy of the direct de-escalation of ICS from long-term triple therapy (tiotropium plus salmeterol/fluticasone) to the once-daily LABA/LAMA combination of indacaterol/glycopyrronium. The primary endpoint was non-inferiority on change from baseline to trough forced expiratory volume in 1 second (FEV1); moderate or severe exacerbations were predefined secondary endpoints.
The direct change to the dual bronchodilator indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in COPD exacerbations. In patients with ≥300 blood eosinophils per µL, there was a greater decline in lung function and increased exacerbation risk, and these patients would be more likely to benefit from continued triple therapy. For most patients, there was no impact on lung function or exacerbations.
This study provides evidence for the personalised management of patients with COPD.