{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:41:10Z","timestamp":1780332070334,"version":"3.54.1"},"reference-count":16,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Arch Biopartners Inc.","award":["NCT04402957"],"award-info":[{"award-number":["NCT04402957"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,2,26]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Phase 2a randomised, placebo-controlled, double-blinded, trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Hospitals in Canada, Turkey and the USA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>A total of 61 subjects with moderate-to-severe COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Randomisation to LSALT peptide 5\u2009mg intravenously daily or placebo for up to 14 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Primary and secondary outcome measures<\/jats:title><jats:p>The primary endpoint was the proportion of subjects alive and free of respiratory failure and\/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O<jats:sub>2<\/jats:sub>\u22656\u2009L\/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8\u2009days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial \" xlink:href=\"NCT04402957\">NCT04402957<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-076142","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T01:24:28Z","timestamp":1716427468000},"page":"e076142","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04402957","registry":"10.18810\/clinical-trials-gov","type":"preResults"},{"clinical-trial-number":"nct03772678","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04402957","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04402957","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-9675","authenticated-orcid":false,"given":"Ranjani","family":"Somayaji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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