| Design | Double-blind, parallel-group RCT |
|---|---|
| Treatment | Fluticasone furoate 100 microg, umeclidinium 62.5 microg and vilanterol 25 microg once daily in a single inhaler |
| Control | Fluticasone furoate/vilanterol, or umeclidinium/vilanterol |
| Population | 10355 patients with symptomatic COPD and at least one exacerbation in the prior year |
| Follow-up | 52 weeks |
| Primary endpoint | Annual rate of moderate or severe COPD exacerbations |
| Result | 0.91 per year with triple therapy versus 1.07 with fluticasone furoate/vilanterol (rate ratio 0.85, 95% CI 0.80 to 0.90, p<0.001) and 1.21 with umeclidinium/vilanterol (rate ratio 0.75, 95% CI 0.70 to 0.81, p<0.001). Severe exacerbations needing admission 0.13 versus 0.19 per year against umeclidinium/vilanterol (rate ratio 0.66, p<0.001). Clinician-diagnosed pneumonia was more frequent with triple therapy than with umeclidinium/vilanterol (HR 1.53, 95% CI 1.22 to 1.92, p<0.001). |
| Secondary endpoints | Time to first exacerbation, trough FEV1, St George's Respiratory Questionnaire, all-cause mortality |
Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate-vilanterol or umeclidinium-vilanterol in this population.
The trial authors, in the published abstract
Around 70% of participants were on an inhaled steroid at entry and had it withdrawn at randomisation, which loads the comparison against the umeclidinium/vilanterol arm. ETHOS reproduced the exacerbation finding with a design less open to that objection, and SUNSET shows what withdrawal actually does. The pneumonia excess is consistent across all of them.
Lipson DA, Barnhart F, Brealey N, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med 2018 May 3;378(18):1671-1680.