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Table 1 Characteristics of included post-hoc analyses of RCTs for meta-analysis

From: Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis

AuthorStudy designStudy size (eosinophil data available)Study armsEosinophil count subgroupsICS effect isolated
Pascoe et al. [20] 2015Two replicate double-blind, parallel group RCTs. Patients were treated with 25 μg vilanterol alone, or 25 μg vilanterol combined with 50 μg, 100 μg or 200 μg fluticasone3177 patients (799 in 25 μg vilanterol alone group, 2378 in fluticasone + vilanterol groups)Fluticasone + vilanterol (all doses) vs. vilanterol< 2% and ≥ 2%; < 150 cells/μL and ≥ 150 cells/μLYes
Barnes et al. [25] (ISOLDE) 2016Double-blind, parallel group, placebo-controlled RCT. Patients were treated with 500 μg fluticasone twice daily or placebo.742 patients (370 fluticasone group, 372 placebo group).Fluticasone vs. placebo< 2% and ≥ 2%Yes
Pavord et al. [26] (INSPIRE) 2016Double-blind, double-dummy, parallel-group RCT. Patients were treated with 500 μg fluticasone + 50 μg salmeterol or 18 μg tiotropium1269 patients (634 fluticasone + salmeterol group, 635 tiotropium group)Fluticasone + salmeterol vs. Tiotropium< 2% and ≥ 2%No
Pavord et al. [26] (TRISTAN I) 2016Double-blind, parallel-group RCT. Patients were treated with 500 μg fluticasone + 50 μg salmeterol or 50 μg salmeterol696 patients (341 fluticasone + salmeterol group, 355 salmeterol group)Fluticasone + salmeterol vs. salmeterol< 2% and ≥ 2%Yes
Pavord et al. [26] (TRISTAN II) 2016Double-blind, parallel-group, placebo-controlled RCT. Patients were treated with 500 μg fluticasone or placebo707 patients (360 fluticasone group, 347 placebo group)Fluticasone vs. placebo< 2% and ≥ 2%Yes
Pavord et al. [26] (SCO30002) 2016Double-blind, parallel-group, placebo-controlled RCT. Patients were treated with 500 μg fluticasone or placebo244 patients (124 fluticasone group, 120 placebo group)Fluticasone vs. placebo< 2% and ≥ 2%Yes
Watz et al. [27] (WISDOM) 2016Double-blind, parallel-group RCT. Patients treated with 18 μg tiotropium daily plus 500 μg fluticasone + 50 μg salmeterol twice daily for 6 weeks. Then randomised to withdrawal of fluticasone or continued triple therapy.2296 patients (1144 ICS-continuation group, 1152 ICS-withdrawal group)Fluticasone + tiotropium + salmeterol vs. tiotropium + salmeterol< 2% and ≥ 2%; < 150 cells/μL and ≥ 150 cells/μL; < 300 cells/μL and ≥ 300 cells/μLYes
Papi et al. [28] (EFFECT) 2017Double-blind, parallel-group RCT. Patients were treated with 500 μg fluticasone + 20 μg formoterol twice daily or formoterol 12 μg twice daily.1177 patients (587 fluticasone + formoterol group, 590 formoterol group)Fluticasone + formoterol vs. formoterol< 2% and ≥ 2%Yes
Vestbo et al. [29] (TRINITY) 2017Double-blind, parallel-group RCT. Patients were treated with 100 μg beclometasone + 6 μg formoterol + 12.5 μg glycopyrronium two puffs twice daily or 18 μg tiotropium2153 patients (1077 fixed triple group, 1076 tiotropium group)Beclometasone + formoterol + glycopyrronium vs. tiotropium< 2% and ≥ 2%No
Roche et al. [30] (FLAME) 2017Double-blind, parallel-group RCT. Patients were treated with 500 μg fluticasone + 50 μg salmeterol twice daily or 110 μg indacaterol + 50 μg glycopyrronium once a day3349 patients (1677 fluticasone + salmeterol group, 1672 indacaterol + glycopyrronium group)Fluticasone + salmeterol vs. indacaterol + glycopyrronium< 2% and ≥ 2%; < 300 cells/μL and ≥ 300 cells/μLNo
Chapman et al. [31] (SUNSET) 2018Double-blind, triple-dummy, parallel-group RCT. Patients were treated with 18 μg tiotropium once daily plus 500 μg fluticasone + 50 μg salmeterol twice daily or 110 μg indacaterol + 50 μg glycopyrronium once a day1051 patients (526 fluticasone + salmeterol + tiotropium group, 527 indacaterol + glycopyrronium group)Fluticasone + tiotropium + salmeterol vs. indacaterol + glycopyrronium< 2% and ≥ 2%; < 300 cells/μL and ≥ 300 cells/μLYes
Papi et al. [32] (TRIBUTE) 2018Double-blind, double-dummy, parallel-group RCT. Patients were treated with 87 μg beclometasone + 5 μg formoterol + 9 μg glycopyrronium two puffs twice daily or 85 μg indacaterol + 43 μg glucopyrronium once a day1532 patients (764 BDP/FF/G, 768 IND/GLY)Beclometasone/formoterol/glycopyrronium vs. indacaterol/ glycopyrronium< 2% and ≥ 2%Yes
Ferguson et al. [33] (KRONOS) 2018Double-blind, parallel-group RCT. Patients were treated with 320 μg budesonide + 18 μg glycopyrolate + 9.6 μg formoterol two puffs twice daily or 18 μg glycopyrolate + 9.6 μg formoterol two puffs twice daily1267 patients (640 BGF, 627 GFF)Budesonide/glycopyrolate/formoterol vs. glycopyrolate/formoterol< 150 cells/μL and ≥ 150 cells/μLYes
Lipson et al. [34] (IMPACT) 2018Double-blind, parallel-group RCT. Patients were treated with 100 μg fluticasone + 62.5 μg umeclidinium + 25 μg vilanterol once daily or 62.5 μg umeclidinium + 25 μg vilanterol once daily6221 patients (4151 triple therapy, 2070 umeclidinium + vilanterol)Fluticasone furoate/umeclidinium/ vilanterol vs. umeclidinium/vilanterol< 150 cells/μL and ≥ 150 cells/μLYes