Table 1 Efficacy trials examining the effects of treatment escalation on overall CID incidence
From: Measuring disease activity in COPD: is clinically important deterioration the answer?
Study description | CID definition | Treatments | Patient population |
|---|---|---|---|
Dual bronchodilator combination therapy | |||
 First retrospective CID analysis of two 24-week double-blind trials [5] | FEV1, SGRQ, exacerbations | UMEC/VI vs placebo, TIO, UMEC or VI | High symptoms, mMRC score ≥ 2, low exacerbation risk |
 Retrospective pooled data from three 6-month double-blind trials [41] | FEV1, SGRQ, exacerbations | UMEC/VI vs TIO | High symptoms, mMRC score ≥ 2, low exacerbation risk. Analyses of the ITT population and maintenance-naïve subgroup (31% of patients) |
 Retrospective pooled analysis of three 26-week, randomized, double-blind trials (SHINE, LANTERN & ILLUMINATE) [38] | Definition 1: FEV1, SGRQ, exacerbations; Definition 2: TDI, SGRQ, exacerbations | IND/GLY vs SFC or TIO | High symptoms, low exacerbation risk (SHINE & LANTERN), exacerbation-free (ILLUMINATE) |
 Retrospective pooled analysis of two 24-week, randomized double-blind trials (AUGMENT & ACLIFORM) [44] | FEV1, SGRQ, TDI, exacerbations | ACL/FORM vs ACL, FORM or placebo | Low to high symptoms, low exacerbation risk |
 Retrospective 52-week randomized double-blind trial (FLAME) [37] | FEV1, SGRQ, exacerbations | IND/GLY vs SFC | High Symptoms, mMRC score ≥ 2, ≥ 1 exacerbation, stable on LAMA for 1 month |
 Retrospective 12-week, randomized, open-label, switching trial (CRYSTAL) [40] | Definition 1: FEV1, TDI, exacerbations; Definition 2: FEV1, CCQ, exacerbations; Definition 3: FEV1, CCQ, TDI, exacerbations | Switch to IND/GLY from previous ICS/LABA or a single LABA or LAMA | Low to high symptoms, low exacerbation risk on open-label therapy, mMRC score ≥ 1 |
 Prospective 24-week, randomized, double-blind trial (EMAX) [46] | Definition 1: FEV1, SGRQ, exacerbations; Definition 2: FEV1, CAT, exacerbations; Definition 3: SGRQ, CAT, TDI, exacerbations | UMEC/VI vs UMEC or SAL | High symptoms, ICS-free population, ≤ 1 moderate exacerbation in the past year |
Multiple inhaler or single inhaler triple therapy | |||
 Retrospective pooled analysis of four 12-week, randomized double-blind trials [43] | FEV1, SGRQ, exacerbations | UMEC vs placebo added to existing open label ICS/LABA therapy | High symptoms, mMRC score ≥ 2, with or without exacerbations |
 Prospective, 52-week, randomized double-blind trial (FULFIL) assessed over 24 weeks (ITT population) and 52 weeks (extension population) [42] | Definition 1: FEV1, SGRQ, exacerbations; Definition 2. FEV1, CAT, exacerbations | FF/UMEC/VI vs BUD/FORM | High symptoms, FEV1 < 50% and CAT ≥ 10 or FEV1 ≥ 50 to < 80% and CAT ≥ 10, and ≥ 2 moderate or ≥ 1 severe exacerbation in the past year |
 Retrospective, three 52-week, randomized, double-blind trials (TRINITY, TRILOGY, TRIBUTE) [45] | Definition 1: FEV1, SGRQ, exacerbations, death; Definition 2 (TRILOGY only): FEV1, SGRQ, exacerbations, TDI, deatha | TRINITY: BDP/FORM/GLY vs TIO (CID 1 & 2) TRILOGY: BDP/FORM/GLY vs BDP/FORM (CID 1) TRIBUTE: BDP/FORM/GLY vs IND/GLY (CID 1) | High symptoms, at-risk population, CAT ≥ 10, FEV1 < 50% predicted plus ≥ 1 exacerbation in last year |