Long-term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in COPD Patients (SUNSET): a Randomized, Double-Blind, Triple-Dummy Clinical Trial.

Rationale: There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations. Objectives: To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD). Methods: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 mu g once daily) or continuation of triple therapy (tiotropium [18 mu g] once daily plus combination of salmeterol/fluticasone propionate [50/500 mu g] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV1. Moderate or severe exacerbations were predefined secondary endpoints. Measurements and Main Results: A total of 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of 226 ml (95% confidence interval, 253 to 1 ml) with confidence limits exceeding the noninferiority margin of 250 ml. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio, 1.08; 95% confidence interval, 0.83 to 1.40). Patients with >= 300 blood eosinophils/mu l at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups. Conclusions: In patients with COPD without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with >= 300 blood eosinophils/mu l suggests that these patients are likely to benefit from triple therapy.