title: FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease.
abstract: 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.
  
  
  
  We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD.
  
  
  
  The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial 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 FEV1and in St. George's Respiratory Questionnaire (SGRQ) total score at Week 24.
  
  
  
  In the intent-to-treat population (n = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899), mean changes from baseline in FEV1were 142 ml (95% confidence interval [CI], 126 to 158) and -29 ml (95% CI, -46 to -13), respectively, and mean changes from baseline in SGRQ scores were -6.6 units (95% CI, -7.4 to -5.7) and -4.3 units (95% CI, -5.2 to -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 therapy versus dual 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.
  
  
  
  These results support the benefits of single-inhaler triple therapy compared with ICS/LABA therapy in patients with advanced COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02345161).
authors.affiliation: 1 GlaxoSmithKline, King of Prussia, Pennsylvania.|2 Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David A
authors.initials: DA
authors.lastname: Lipson
authors.affiliation: 3 GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Barnacle
authors.affiliation: 3 GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom.
authors.forename: Ruby
authors.initials: R
authors.lastname: Birk
authors.affiliation: 3 GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom.
authors.forename: Noushin
authors.initials: N
authors.lastname: Brealey
authors.affiliation: 1 GlaxoSmithKline, King of Prussia, Pennsylvania.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Locantore
authors.affiliation: 4 UCL Respiratory, University College London, London, United Kingdom; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: 5 KLB Health Research, Lübeck, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ludwig-Sengpiel
authors.affiliation: 3 GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom.
authors.forename: Rajat
authors.initials: R
authors.lastname: Mohindra
authors.affiliation: 3 GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom.
authors.forename: Maggie
authors.initials: M
authors.lastname: Tabberer
authors.affiliation: 3 GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhu
authors.affiliation: 1 GlaxoSmithKline, King of Prussia, Pennsylvania.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Pascoe
mesh_terms: D000280:Administration, Inhalation; D000730:Androstadienes / Q000627:therapeutic use*; D001592:Benzyl Alcohols / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D019819:Budesonide / Q000627:therapeutic use*; D002722:Chlorobenzenes / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D011812:Quinuclidines / Q000627:therapeutic use*
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; C573971:GSK573719; D011812:Quinuclidines; C550468:vilanterol; D019819:Budesonide; C523187:fluticasone furoate; D000068759:Formoterol Fumarate
keywords: chronic obstructive pulmonary disease; health-related quality of life; lung function; single-inhaler triple therapy