Direct de-escalation from long-term triple therapy
SUNSET trial design and results
Design
Double-blind, triple-dummy, non-inferiority RCT
Treatment
Direct switch to indacaterol 110 microg / glycopyrronium 50 microg once daily
Control
Continued triple therapy: tiotropium 18 microg daily plus salmeterol/fluticasone 50/500 microg twice daily
Population
Non-frequently-exacerbating patients with moderate-to-severe COPD on long-term triple therapy
Follow-up
26 weeks
Primary endpoint
Non-inferiority for change from baseline in trough FEV1
Result
De-escalation caused a small fall in lung function with no difference in exacerbation rate. Patients with blood eosinophils at or above 300 cells/microlitre carried a higher exacerbation risk after withdrawal.
Secondary endpoints
Moderate or severe exacerbations, eosinophil subgroups
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 trial authors, in the published abstract
How it has aged
The practical counterweight to IMPACT and ETHOS: not everyone on triple therapy needs to stay on it. The eosinophil threshold it identified is now the standard way of deciding who can safely have the steroid withdrawn.
Publications
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
Chapman KR, Hurst JR, Frent SM, et al. 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.
Small decrease in trough FEV1 after withdrawal of the inhaled steroid
No difference in exacerbation rate overall
Higher exacerbation risk after withdrawal when blood eosinophils were 300 cells/microlitre or above