{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:00:52Z","timestamp":1793829652287,"version":"4.6.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":1829,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide\/glycopyrrolate\/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate\/formoterol fumarate (GFF). However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320\/18\/9.6 \u03bcg of BGF (BGF 320), 160\/18\/9.6 \u03bcg of BGF (BGF 160), 18\/9.6 \u03bcg of GFF, or 320\/9.6 \u03bcg of budesonide\/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler). Time to death (all-cause) was a prespecified secondary endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33\u20130.80; unadjusted P\u2009=\u20090.0035). There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44\u20131.16; P\u2009=\u20090.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator. Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis. Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD. Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202006-2618oc","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T13:30:41Z","timestamp":1606743041000},"page":"553-564","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":255,"title":["Reduced All-Cause Mortality in the ETHOS Trial of Budesonide\/Glycopyrrolate\/Formoterol for Chronic Obstructive Pulmonary Disease. A Randomized, Double-Blind, Multicenter, Parallel-Group Study"],"prefix":"10.1093","volume":"203","author":[{"given":"Fernando J.","family":"Martinez","sequence":"first","affiliation":[{"name":"Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus F.","family":"Rabe","sequence":"additional","affiliation":[{"name":"LungenClinic Grosshansdorf and Christian-Albrechts University Kiel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary T.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Pulmonary Research Institute of Southeast Michigan, Farmington Hills, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadwiga A.","family":"Wedzicha","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Hospitals Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Centre for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Rossman","sequence":"additional","affiliation":[{"name":"AstraZeneca, Morristown, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Earl","family":"St. Rose","sequence":"additional","affiliation":[{"name":"AstraZeneca, Morristown, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopa","family":"Trivedi","sequence":"additional","affiliation":[{"name":"AstraZeneca, Durham, North 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