{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T09:37:45Z","timestamp":1771580265468,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID\u201019. UFH has antiviral effects and prevents the SARS\u2010CoV\u20102 virus' entry into mammalian cells. In addition, UFH has significant anti\u2010inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID\u201019 (INHALE\u2010HEP) metatrial is a prospective individual patient data analysis of on\u2010going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS\u2010CoV\u20102 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time\u2010to\u2010event analyses. Individual studies may have additional outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Analysis<\/jats:title><jats:p>We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention\u2010to\u2010treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow\u2010up or withdrawn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration, ethics and dissemination<\/jats:title><jats:p>The metatrial is registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14714","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T08:29:55Z","timestamp":1609316995000},"page":"3075-3091","source":"Crossref","is-referenced-by-count":22,"title":["INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID\u201019 (INHALE\u2010HEP): Protocol and statistical analysis plan for an investigator\u2010initiated international metatrial of randomised studies"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-4229","authenticated-orcid":false,"given":"Frank M.P.","family":"van Haren","sequence":"first","affiliation":[{"name":"Australian National University College of Health and Medicine  Canberra Australia"},{"name":"Faculty of Health University of Canberra  Canberra 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