Abstract
There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 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-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.
Keywords: ARDS; COVID-19; RCT; SARS; SARS-CoV-2; meta-trial; nebulised heparin; pandemic; randomised study; respiratory failure; unfractionated heparin.
【저자키워드】 COVID-19, SARS-CoV-2, ARDS, pandemic, Respiratory failure, SARS, RCT, meta-trial, nebulised heparin, randomised study, unfractionated heparin., 【초록키워드】 ARDS, COVID-19 pneumonia, clinical trial, therapy, Respiratory failure, thrombosis, randomised, Anti-inflammatory, Pneumonia, Infection, lung, extubation, SARS-CoV-2 virus, Lung injury, progression, heparin, invasive ventilation, Laboratory, Coagulation, Inhaled, Ventilator-free days, Placebo, dataset, placebo-controlled, Evidence, Analysis, endpoints, meta-trial, patient data, Microvascular thrombosis, unfractionated heparin, Activation, Primary outcome, standard care, open label, controlled clinical trials, FIBRIN, hypoxaemic respiratory failure, mammalian cells, Effect, country, FIVE, Prevent, limit, alveolar fibrin, defined, resulting, blinded, receive, Can, days alive, patients with COVID-19, randomised controlled, the SARS-CoV-2 virus, ventilator-free day, with COVID-19, 【제목키워드】 randomised, International, Statistical analysis plan, clinical study, Can, investigator-initiated, patients with COVID-19,