RATIONALE: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited. OBJECTIVES: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy. METHODS: FULFIL was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA(®) inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler(®)). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough forced expiratory volume in 1 second (FEV1) and in St George's Respiratory Questionnaire (SGRQ) Total score, at Week 24. MEASUREMENTS AND MAIN RESULTS: In the intent-to-treat population (N = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899): mean change from baseline in FEV1 was 142 mL (95% confidence interval [CI], 126,158) and -29 mL (95% CI, -46,-13), respectively; mean change from baseline SGRQ was -6.6 units (95% CI, -7.4,-5.7) and -4.3 units (95% CI, -5.2,-3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple versus ICS/LABA therapy (35% reduction, 95% CI, 14,51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components. CONCLUSIONS: These results support the benefits of single inhaler triple therapy compared with ICS/LABA therapy, in patients with advanced COPD. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02345161
