TY - JOUR T1 - Dipeptidyl Peptidase-1 Inhibition in Patients Hospitalized with COVID-19: a Multicentre Randomized Double-Blind Placebo Controlled Trial JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2022.RCT2883 VL - 60 IS - suppl 66 SP - RCT2883 AU - Holly R. Keir AU - Merete B. Long AU - Hani Abo-Leyah AU - Yan H. Giam AU - Thenmalar Vadiveloo AU - Thomas Pembridge AU - Rebecca C. Hull AU - Lilia Delgado AU - Margaret Band AU - Fiona Mclaren-Neil AU - Simon Adamson AU - Eva Lahnsteiner AU - Amy Gilmour AU - Chloe Hughes AU - Benjamin Jm. New AU - David Connell AU - Rebecca Dowey AU - Helena Turton AU - Hollian Richardson AU - Diane Cassidy AU - Jamie Cooper AU - Jay Suntharalingam AU - Lavanya Diwakar AU - Peter Russell AU - Jonathan Underwood AU - Alexander Hicks AU - Davinder Ps Dosanjh AU - Beth Sage AU - Devesh Dhasmana AU - Mark Spears AU - Aa Roger Thompson AU - Christopher Brightling AU - Andrew Smith AU - Manish Patel AU - Jacob George AU - Alison M Condliffe AU - Amelia Shoemark AU - Graeme Maclennan AU - James D Chalmers Y1 - 2022/09/04 UR - http://erj.ersjournals.com/content/60/suppl_66/RCT2883.abstract N2 - Background: Neutrophil serine proteases (NSPs) are involved in the pathogenesis of  COVID19 and are increased in severe and fatal infection. We investigated whether treatment with Brensocatib, an inhibitor of dipeptidyl peptidase-1, an enzyme responsible for the activation of NSPs, would improve outcomes in hospitalized patients with COVID19.Methods: In a randomized, double-blind, placebo-controlled trial, 406 hospitalized patients with COVID19 with at least one risk factor for severe disease were randomized 1:1 to once-daily Brensocatib 25mg (n=192) or placebo (n=214) for 28 days. Primary outcome was the 7-point World Health Organisation Clinical Status scale at day 29. Secondary outcomes included time to clinical improvement, national early warning score, new oxygen and ventilation use, neutrophil elastase activity in blood and mortality.Findings: Brensocatib treatment was associated with worse clinical status at day 29 (adjusted odds ratio 0·72, 95%CI 0·57-0·92) compared to placebo. The adjusted hazard ratio (aHR) for time to clinical improvement was 0·87 (95%CI 0·76-1·00) and time to hospital discharge was 0·98 (95%CI 0·84-1·13).  During the 28-day follow-up period, 23 (11%) and 29 (15%) patients died in the placebo and Brensocatib treated groups respectively). Oxygen and new ventilation use were greater in the Brensocatib treated patients. Neutrophil elastase activity in blood was significantly reduced in the Brensocatib group from baseline to day 29. Prespecified subgroup analyses of the primary outcome supported the primary results.Interpretation: Brensocatib treatment did not improve day 29 clinical status in hospitalised patients with COVID19FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, RCT2883.This article was presented at the 2022 ERS International Congress, in session “ALERT 1: COPD and hospital management”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -