A phase III study of triple therapy with budesonide/glycopyrrolate/ formoterol fumarate metered dose inhaler 320/18/9.6 μg and 160/18/9.6 μg using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol

Background: Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta(2)-agonist (ICS/LAMA/LABAs) are an emerging treatment option for chronic obstructive pulmonary disease (COPD). Nevertheless, questions remain regarding the optimal patient population for triple therapy as well as the benefit:risk ratio of ICS treatment. Methods: ETHOS is an ongoing, randomized, double-blind, multicenter, parallel-group, 52-week study in symptomatic patients with moderate-to-very severe COPD and a history of exacerbation(s) in the previous year. Two doses of single inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI 320/18/9.6 mu g and 160/18/9.6 mu g) will be compared to glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 mu g and budesonide/formoterol fumarate (BFF) MDI 320/9.6 mu g, all formulated using co-suspension delivery technology. Outcomes include the rate of moderate/severe (primary endpoint) and severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies will assess lung function and cardiovascular safety. Study population: From June 2015-July 2018, 16,044 patients were screened and 8572 were randomized. Preliminary baseline demographics show that 55.9% of patients had experienced >= 2 moderate/severe exacerbations in the previous year, 79.1% were receiving an ICS-containing treatment at study entry, and 59.9% had blood eosinophil counts >= 150 cells/mm(3). Conclusions: ETHOS will provide data on exacerbations, patient-reported outcomes, mortality, and safety in 8572 patients with moderate-to-very severe COPD receiving triple and dual fixed-dose combinations. For the first time, ICS/LAMA/LABA triple therapy with two different doses of ICS will be compared to dual ICS/LABA and LAMA/LABA therapies.