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Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID‐19 Requiring invasive ventilation Meta‐Trial (CHARTER‐MT): Protocol and statistical analysis plan for an investigator‐initiated international meta‐trial of prospective randomised clinical studies
Author(s) -
Haren Frank M. P.,
Laffey John G.,
Artigas Antonio,
Page Clive,
Schultz Marcus J.,
Cosgrave David,
McNicholas Bairbre,
Smoot Thomas L.,
Nunes Quentin,
Richardson Alice,
Yoon HwanJin,
Loon Lex M.,
Ghosh Angajendra,
Said Simone,
Panwar Rakshit,
Smith Roger,
Santamaria John D.,
Dixon Barry
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.15253
Subject(s) - medicine , heparin , mechanical ventilation , intensive care medicine , context (archaeology) , pneumonia , placebo , anesthesia , pathology , alternative medicine , paleontology , biology
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 C an nebulised H ep A rin R educe mor T ality and time to E xtubation in Patients with COVID‐19 R equiring invasive ventilation M eta‐ T rial (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.