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The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID\u201019 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS\u2010CoV\u20102 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti\u2010inflammatory and mucolytic properties that may be useful in this context.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and intervention<\/jats:title><jats:p>The <jats:styled-content>C<\/jats:styled-content>an nebulised <jats:styled-content>H<\/jats:styled-content>ep<jats:styled-content>A<\/jats:styled-content>rin <jats:styled-content>R<\/jats:styled-content>educe mor<jats:styled-content>T<\/jats:styled-content>ality and time to <jats:styled-content>E<\/jats:styled-content>xtubation in Patients with COVID\u201019 <jats:styled-content>R<\/jats:styled-content>equiring invasive ventilation <jats:styled-content>M<\/jats:styled-content>eta\u2010<jats:styled-content>T<\/jats:styled-content>rial (CHARTER\u2010MT) is a collaborative prospective individual patient data analysis of on\u2010going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID\u201019 requiring invasive ventilation on various endpoints.<\/jats:p><jats:p>Each constituent study will randomise patients with COVID\u201019 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo\u2010controlled studies) while under invasive ventilation. Each participating study collect a pre\u2010defined minimum dataset. The primary outcome for the meta\u2010trial is the number of ventilator\u2010free days up to day 28\u2009day, defined as days alive and free from invasive ventilation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15253","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T02:50:47Z","timestamp":1643770247000},"page":"3272-3287","source":"Crossref","is-referenced-by-count":13,"title":["Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID\u201019 Requiring invasive ventilation Meta\u2010Trial (CHARTER\u2010MT): Protocol and statistical analysis plan for an investigator\u2010initiated international meta\u2010trial of prospective randomised clinical studies"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-4229","authenticated-orcid":false,"given":"Frank M. 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