Table 1.
Details of included RCTs
| Number | Study | Study design | Duration of follow-up | Inclusion criteria | Exclusion criteria | Drugs, Doses (μg), Regimen, Device | No of patients |
|---|---|---|---|---|---|---|---|
| 1 | TRILOGY Singh, 2016 | A randomized, parallel group, double-blind, active-controlled study | 52 weeks | FEV1 < 50% predicted, moderate or severe COPD exacerbation in the previous 12 months ≥ 1, CAT score ≥ 10, BDI score ≤ 10 | Asthma, history of allergic rhinitis; clinically significant cardiovascular conditions | BDP/FOR/GLY (100/6/12.5) bid MDI | 687 |
| BDP/FOR (100/6) bid MDI | 680 | ||||||
| 2 | FULFIL Lipson,2017 | A phase 3, randomized, double-blind, double-dummy, parallel-group, multicentre study | 24 weeks | FEV1 < 50% predicted and CAT score ≥ 10; 50% ≤ FEV1 < 80% predicted and CAT score ≥ 10 or moderate COPD exacerbation in the previous 12 months ≥ 2 or severe COPD exacerbation in the previous 12 months ≥ 1 | Asthma, unresolved pneumonia, severe COPD exacerbation | FF/UMEC/VI (100/62.5/25) od DPI | 911 |
| BUD/FOR (400/12) bid DPI | 899 | ||||||
| 3 | IMPACT Lipson,2018 | A phase 3, randomized, double-blind, parallel-group, multicentre trial | 52 weeks | FEV1 < 50% predicted and moderate or severe COPD exacerbation in the previous 12 months ≥ 1; 50% ≤ FEV1 < 80% predicted and moderate COPD exacerbation in the previous 12 months ≥ 2 or severe COPD exacerbation in the previous 12 months ≥ 1 | Not reported | FF/UMEC/VI (100/62.5/25) od DPI | 4151 |
| FF/VI (100/25) od DPI | 4134 | ||||||
| UMEC/VI (62.5/25) od DPI | 2070 | ||||||
| 4 | KRONOS Ferguson,2018 | A randomized, double-blind, parallel-group, phase 3 randomized controlled trial | 24 weeks | 25% ≤ FEV1 < 80% predicted; CAT score ≥ 10. Patients were not required to have had a COPD exacerbation within the preceding year | Asthma, diagnosis of any respiratory disease | BUD/GLY/FOR (320/18/9.6) bid MDI | 639 |
| GLY/FOR (18/9.6) bid MDI | 625 | ||||||
| BUD/FOR (320/9.6) bid MDI | 314 | ||||||
| 5 | TRIBUTE Papi,2018 | A randomized, parallel-group, double-blind, double-dummy, active-controlled phase 3b study | 52 weeks | FEV1 < 50%, a moderate or severe COPD exacerbation in the previous 12 months ≥ 1, CAT score ≥ 10 | Asthma; clinically significant cardiovascular disorders | BDP/FOR/GLY (100/6/10) bid MDI | 764 |
| IND/GLY (85/43) od DPI | 768 | ||||||
| 6 | ETHOS Rabe,2020 | A phase 3, randomized, double-blind, parallel-group, multicentre trial | 52 weeks | FEV1 < 50% predicted and moderate or severe COPD exacerbation in the previous 12 months ≥ 1; FEV1 ≥ 50% predicted and moderate COPD exacerbation in the previous 12 months ≥ 2 or severe COPD exacerbation in the previous 12 months ≥ 1, CAT ≥ 10 | Current diagnosis of asthma | BUD/GLY/FOR (320/18/9.6) bid MDI | 2144 |
| BUD/GLY/FOR (160/18/9.6) bid MDI | 2124 | ||||||
| BUD/FOR (320/9.6) bid MDI | 2136 | ||||||
| GLY/FOR (18/9.6) bid MDI | 2125 |
BDP/FOR/GLY: beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide; BUD/GLY/FOR: budesonide/glycopyrronium bromide/formoterol fumarate; FF/UMEC/VI: fluticasone furoate/umeclidinium/vilanterol; BDP/FOR: beclomethasone dipropionate/formoterol fumarate; BUD/FOR: budesonide/formoterol fumarate; UMEC/VI: umeclidinium bromide/vilanterol; GLY/FOR: glycopyrronium bromide/formoterol fumarate; IND/GLY: indacaterol/glycopyrronium bromide; OD: once daily; BID: twice daily; MDI: metered-dose inhaler formulation; DPI: dry powder inhaler formulation; FEV1: forced expiratory volume in 1 s; BDI: Baseline Dyspnea Index; CAT: COPD assessment test; RCT: Randomized controlled trial