Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Symptoms and Quality of Life

Adv Ther. 2018 Jan;35(1):56-71. doi: 10.1007/s12325-017-0650-4. Epub 2018 Jan 8.


Introduction: Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies. The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses. FULFIL co-primary endpoint data have been previously reported.

Methods: FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β2-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations. A subset participated for 52 weeks. Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD™ (E-RS: COPD), St George's Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.

Results: FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period. FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR. At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).

Conclusion: These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR. The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.

Trial registration: ClinicalTrials.gov number: NCT02345161.

Funding: GSK.

Keywords: Budesonide/formoterol; COPD burden; Fluticasone furoate/umeclidinium/vilanterol; Patient-reported outcomes; Respiratory; Symptom burden.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adult
  • Benzyl Alcohols / administration & dosage
  • Benzyl Alcohols / adverse effects
  • Benzyl Alcohols / therapeutic use*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Budesonide, Formoterol Fumarate Drug Combination / therapeutic use
  • Chlorobenzenes / administration & dosage
  • Chlorobenzenes / adverse effects
  • Chlorobenzenes / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Dyspnea / drug therapy
  • Female
  • Fluticasone / administration & dosage
  • Fluticasone / adverse effects
  • Fluticasone / therapeutic use*
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quality of Life
  • Quinuclidines / administration & dosage
  • Quinuclidines / adverse effects
  • Quinuclidines / therapeutic use*
  • Surveys and Questionnaires


  • Benzyl Alcohols
  • Bronchodilator Agents
  • Budesonide, Formoterol Fumarate Drug Combination
  • Chlorobenzenes
  • GSK573719
  • Quinuclidines
  • vilanterol
  • Fluticasone

Associated data

  • ClinicalTrials.gov/NCT02345161