Study | Design and trial length | COPD diagnosis criteria and severity | Age range (years) | Intervention | Treatment duration and follow-up frequency | Primary efficacy | Other outcomes |

Outcome | |||||||

Pauwels 24 | Parallel, double-blind, placebo-controlled, international, multicentre | Spirometry test | 30–65 | Budesonide 400 µg two times per day (n=458) | 3 years; | Change in post-bronchodilator FEV_{1} over time | None |

(9 European countries); | 50% < FEV_{1} < 100% | Placebo (n=454) | Every 3 months | (mL/yr) | |||

3.5 years | |||||||

Zheng22 | Parallel, double-blind, placebo-controlled, multicentre (China); | Spirometry test | 40–79 | Fluticasone propionate/salmeterol 500/50 µg two times per day (n=297) | 6 months; | Pre-bronchodilator FEV_{1} (mL) | Post-bronchodilator FEV_{1} (L) |

6.5 months | 25% < FEV_{1} < 69% | Placebo (n=148) | Week 0,2,4,8,12,16,20 and 24 | Health status | |||

Night-time awakenings | |||||||

Supplemental salbutamol use | |||||||

Snoeck-Stroband 18 | Post-hoc analysis. Parallel, double-blind, placebo and active controlled, single centre (Netherlands); | Spirometry test | 45–75 | Fluticasone propionate 500 µg two times per day (n=26) | 2.5 years; | Inflammatory cell counts in bronchial biopsies (10^{7}/m2) and induced sputum (10^{4}/mL) | Post-bronchodilator FEV_{1} (L) |

7 years | 30% < FEV_{1} < 80% | Placebo (n=24) | Every 3 months | Dyspnoea score | |||

Health status | |||||||

Wedzicha 23 | Parallel, double-blind, non-inferiority, multicentre (43 countries worldwide) ; 52 weeks | Spirometry test | ≥40 | Indacterol/glycopyrronium 110/50 µg (n=1680) | Exacerbations at week 52 | Annual rate of COPD exacerbations | None |

25% < FEV_{1} < 60% | Salmeterol/fluticasone propionate 50/500 µg (n=1682) | ||||||

mMRC ≥2; ≥1 exacerbation in past year | |||||||

Hinds20 | Secondary analysis. Randomised, double-blind, parallel group, 52 week, multicentre study (16 countries worldwide) | FEV_{1} of ≤70% predicted and a (FVC) ratio of ≤0.7 after bronchodilator use; ≥1 exacerbation in previous year | ≥40 | Fluticasone furoate/vilanterol 50/25 µg OR 100/25 µg OR 200/25 µg two times per day (n=1092) | 52 weeks | Annual rate of moderate-to-severe exacerbations | None |

Vilanterol 25 µg (n=386) | |||||||

Bhatt21 | Prespecified secondary analysis. Randomised, double-blind, 52 week, multicentre (43 countries worldwide) | FEV_{1} of 50%–70% predicted and a (FVC) ratio of ≤0.7 after bronchodilator use; ≥10 pack-year smoking history | 40–80 | Fluticasone furoate/vilanterol 100/25 µg (n=4121) | 3, 6, 9 and 12 months | Change in post-bronchodilator FEV_{1} | Annual rate of moderate-to-severe exacerbations |

Fluticasone furoate 100 µg (n-4135) | |||||||

Vilanterol 25 µg (n=4118) | SGRQ | ||||||

Placebo (n=4111) | |||||||

Pascoe 19 | Secondary analysis. Randomised, double-blind, parallel, 52 week, multicentre | CAT score ≥10, FEV_{1} ≤50% and ≥1 moderate/severe exacerbation in last year OR FEV_{1} 50%–80% and ≥2 moderate/severe exacerbation in last year | ≥40 | Fluticasone furoate/vilanterol 100/25 µg (n=4125) | 52 weeks | Annual rate of moderate-to-severe exacerbations | SGRQ |

Umeclidinium/vilanterol 62.5/25 µg (n=2065) |

CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FEV

_{1}, forced expiratory volume in 1 s; FVC, forced vital capacity; µg, micrograms; mL/yr, millilitres per year; mMRC, modified Medical Research Council dyspnoea scale; SGRQ, St. George's Respiratory Questionnaire.