Table 1.
Main characteristics of the RCTs included in the network meta-analysis.
| Author, Year, Clinical Trial Identifier, Study Name, and Reference | Trial Characteristics | Duration of Treatment (Weeks) | Number of Analyzed Patients | Drugs, Doses, Regimen of Administration, Device | Main Inclusion Criteria | Age (Years) | Male (%) | Current Smokers (%) | Smoking History (Pack-Years) | Post Bronchodilator FEV1 (% Predicted) | Reversibility (% Patients) | Patient with AECOPD History (%) | AECOPD in the Previous Year (Rate) | Blood Eosinophil Count at Baseline (Cells per µL) | Blood Eosinophils Subgroups (Cells per µL) | Jadad Score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rabe et al., 2021, NCT02465567, ETHOS pulmonary function test sub-study [31] | Phase III, randomized, double-blind, parallel-group, active control, multicenter | 52 | 3088 | BUD/GLY/FOR (320/18/9.6 μg BID via MDI); BUD/GLY/FOR (160/18/9.6 μg BID via MDI); GLY/FOR (18/9.6 μg BID via MDI); BUD/FOR (320/9.6 μg BID via MDI) | Pre-bronchodilator FEV1 < 65% predicted | 64.4 | 47.2 | 44.0 | 43.9 | 42.8 | 34.1 | 100.0 | 1.5 | NA | <150; ≥150 | 4 |
| Rabe et al., 2020, NCT02465567, ETHOS [14,33] | Phase III, randomized, double-blind, parallel-group, active control, multicenter | 52 | 8509 | BUD/GLY/FOR (320/18/9.6 μg BID via MDI); BUD/GLY/FOR (160/18/9.6 μg BID via MDI); GLY/FOR (18/9.6 μg BID via MDI); BUD/FOR (320/9.6 μg BID via MDI) | Post-bronchodilator FEV1 ≥ 25% and ≤65% predicted | 64.7 | 59.7 | 41.1 | 47.6 | 43.4 | 30.7 | 100.0 | 1.7 | 167 | <150; ≥150 | 4 |
| Tabberer et al., 2020, NCT02164513, IMPACT sub-study [32] | Phase III, randomized, double-blind, parallel-group, active control, multicenter | 52 | 5058 | FF/UMEC/VI (100/62.5/25 μg QD via DPI); UMEC/VI (62.5/25 μg QD via DPI); FF/VI (100/25 μg QD via DPI) | (a) Post-bronchodilator FEV1 < 50% predicted and ≥1 moderate or severe AECOPD in the previous year; (b) post-bronchodilator FEV1 ≥ 50% and ≤80% predicted and ≥2 moderate or ≥1 severe AECOPD in the previous year | 64.7 | 56.0 | NA | NA | NA | NA | NA | NA | NA | NA | 3 |
| Ferguson et al., 2018, NCT02497001, KRONOS [30] | Phase III, randomized, double-blind, parallel-group, active control, multicenter | 24 | 1578 | BUD/GLY/FOR (320/18/9.6 μg BID via MDI); GLY/FOR (18/9.6 μg BID via MDI); BUD/FOR (320/9.6 μg BID via MDI) | Post-bronchodilator FEV1 ≥ 25% and ≤80% predicted | 65.1 | 70.6 | 39.3 | 45.0 | 50.1 | 42.9 | 25.4 | 0.3 | 153 | <150; ≥150 | 5 |
| Lipson et al., 2018, NCT02164513, IMPACT [15,34] | Phase III, randomized, double-blind, parallel-group, active control, multicenter | 52 | 10,355 | FF/UMEC/VI (100/62.5/25 μg QD via DPI); UMEC/VI (62.5/25 μg QD via DPI); FF/VI (100/25 μg QD via DPI) | (a) Post-bronchodilator FEV1 < 50% predicted and ≥1 moderate or severe AECOPD in the previous year; (b) post-bronchodilator FEV1 ≥ 50% and ≤80% predicted and ≥2 moderate or ≥1 severe AECOPD in the previous year | 65.3 | 66.0 | 35.0 | ≥10.0 | 45.5 | 18.0 | 100.0 | 1.7 | ≃150 | <150; ≥150 | 3 |
| Singh et al., 2016, NCT01917331, TRILOGY [16] | Phase III, randomized, double-blind, parallel-group, active control, multicenter | 52 | 1367 | BDP/FOR/GLY (200/12/25 μg BID via MDI); BDP/FOR (200/12 μg BID via MDI) | Post-bronchodilator FEV1 < 50% predicted and ≥1 moderate or severe AECOPD in the previous year | 63.6 | 75.5 | 47.0 | ≥10.0 | 36.6 | NA | 100.0 | 1.2 | 245 | <200; ≥200 | 5 |
Reversibility was defined as an increase in FEV1 of ≥12% and >200 mL following administration of salbutamol. AECOPD: acute exacerbation of COPD; BID: bis in die, twice daily; BDP: beclomethasone dipropionate; BUD: budesonide; COPD: chronic obstructive pulmonary disease; DPI: dry-powder inhaler; FEV1: forced expiratory volume in the first second; FOR: formoterol fumarate; FF: fluticasone furoate; GLY: glycopyrronium bromide or glycopyrrolate; MDI: metered-dose inhaler; NA: not available; QD: quaque die, once daily; RCT: randomized controlled trial; UMinconsistency in network metaRisk-of-bias VISuaEC: umeclidinium bromide; VI: vilanterol.