{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T02:32:11Z","timestamp":1777429931903,"version":"3.51.4"},"reference-count":49,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2023,1,31]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the availability of COVID-19 vaccinations, there remains a need to investigate treatments to reduce the risk or severity of potentially fatal complications of COVID-19, such as acute respiratory distress syndrome (ARDS). This study evaluated the efficacy and safety of the transient receptor potential channel C6 (TRPC6) inhibitor, BI 764198, in reducing the risk and\/or severity of ARDS in patients hospitalised for COVID-19 and requiring non-invasive, supplemental oxygen support (oxygen by mask or nasal prongs, oxygen by non-invasive ventilation or high-flow nasal oxygen).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multicentre, double-blind, randomised phase II trial comparing once-daily oral BI 764198 (n=65) with placebo (n=64) for 28 days (+2-month follow-up). Primary endpoint: proportion of patients alive and free of mechanical ventilation at day 29. Secondary endpoints: proportion of patients alive and discharged without oxygen (day 29); occurrence of either in-hospital mortality, intensive care unit admission or mechanical ventilation (day 29); time to first response (clinical improvement\/recovery); ventilator-free days (day 29); and mortality (days 15, 29, 60 and 90).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No difference was observed for the primary endpoint: BI 764198 (83.1%) versus placebo (87.5%) (estimated risk difference \u20135.39%; 95% CI \u201316.08 to 5.30; p=0.323). For secondary endpoints, a longer time to first response (rate ratio 0.67; 95% CI 0.46 to 0.99; p=0.045) and longer hospitalisation (+3.41 days; 95% CI 0.49 to 6.34; p=0.023) for BI 764198 versus placebo was observed; no other significant differences were observed. On-treatment adverse events were similar between trial arms and more fatal events were reported for BI 764198 (n=7) versus placebo (n=2). Treatment was stopped early based on an interim observation of a lack of efficacy and an imbalance of fatal events (Data Monitoring Committee recommendation).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TRPC6 inhibition was not effective in reducing the risk and\/or severity of ARDS in patients with COVID-19 requiring non-invasive, supplemental oxygen support.<\/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\" xlink:href=\"NCT04604184\">NCT04604184<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/thorax-2022-219668","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T15:05:13Z","timestamp":1680793513000},"page":"816-824","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["TRPC6 inhibitor (BI 764198) to reduce risk and severity of ARDS due to COVID-19: a phase II randomised controlled trial"],"prefix":"10.1136","volume":"78","clinical-trial-number":[{"clinical-trial-number":"nct04604184","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03854552","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04102462","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Lorraine B","family":"Ware","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nima","family":"Soleymanlou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny Francis","family":"McAuley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Estrada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George A","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Lacamera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renee","family":"Kaste","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wansuk","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhya","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Welte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"2024051320382765000_78.8.816.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002032"},{"key":"2024051320382765000_78.8.816.2","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0384-2020","article-title":"Current evidence for COVID-19 therapies: a systematic literature review","volume":"30","author":"Welte","year":"2021","journal-title":"Eur Respir Rev"},{"key":"2024051320382765000_78.8.816.3","unstructured":"Centers for Disease Control and Prevention (CDC) . 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Pathophysiology of acute respiratory distress syndrome. In: Webb A , Angus D , Finfer S , et al , eds. Oxford Textbook of Critical Care. Oxford University Press, 2016: 497\u2013500.","DOI":"10.1093\/med\/9780199600830.003.0108"},{"key":"2024051320382765000_78.8.816.23","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201308-280OC"},{"key":"2024051320382765000_78.8.816.24","unstructured":"GTEx Portal . Gene page. 2021. Available: https:\/\/gtexportal.org\/home\/gene\/TRPC6 [Accessed 1 Nov 2021]."},{"key":"2024051320382765000_78.8.816.25","doi-asserted-by":"crossref","DOI":"10.3390\/ph12010023","article-title":"Modulators of transient receptor potential (Trp) channels as therapeutic options in lung disease","volume":"12","author":"Dietrich","year":"2019","journal-title":"Pharmaceuticals (Basel)"},{"key":"2024051320382765000_78.8.816.26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608288200"},{"key":"2024051320382765000_78.8.816.27","unstructured":"ClinicalTrials.gov . 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