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

Am J Respir Crit Care Med. 2018 Aug 1;198(3):329-339. doi: 10.1164/rccm.201803-0405OC.


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 μg once daily) or continuation of triple therapy (tiotropium [18 μg] once daily plus combination of salmeterol/fluticasone propionate [50/500 μg] 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 -26 ml (95% confidence interval, -53 to 1 ml) with confidence limits exceeding the noninferiority margin of -50 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/μl 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/μl suggests that these patients are likely to benefit from triple therapy. Clinical trial registered with www.clinicaltrials.gov (NCT 02603393).

Trial registration: ClinicalTrials.gov NCT02603393.

Keywords: COPD; exacerbation; indacaterol/glycopyrronium; lung function; triple therapy.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Bronchodilator Agents / therapeutic use
  • Double-Blind Method
  • Female
  • Fluticasone-Salmeterol Drug Combination / therapeutic use
  • Glucocorticoids / therapeutic use*
  • Glycopyrrolate / therapeutic use*
  • Humans
  • Indans / therapeutic use*
  • Male
  • Muscarinic Antagonists / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quinolones / therapeutic use*
  • Tiotropium Bromide / therapeutic use
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Fluticasone-Salmeterol Drug Combination
  • Glucocorticoids
  • Indans
  • Muscarinic Antagonists
  • Quinolones
  • indacaterol
  • Glycopyrrolate
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT02603393