FULFIL Trial: Once-Daily Triple Therapy for Patients With Chronic Obstructive Pulmonary Disease

Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-446. doi: 10.1164/rccm.201703-0449OC.

Abstract

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 in patients with COPD.

Methods: 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 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 changes from baseline in FEV1 were 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.

Conclusions: 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).

Keywords: chronic obstructive pulmonary disease; health-related quality of life; lung function; single-inhaler triple therapy.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Androstadienes / therapeutic use*
  • Benzyl Alcohols / therapeutic use*
  • Bronchodilator Agents / therapeutic use
  • Budesonide / therapeutic use*
  • Chlorobenzenes / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume / drug effects
  • Formoterol Fumarate / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quality of Life
  • Quinuclidines / therapeutic use*

Substances

  • Androstadienes
  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • GSK573719
  • Quinuclidines
  • vilanterol
  • Budesonide
  • fluticasone furoate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT02345161