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
Issued Date
2022-07-01
Resource Type
ISSN
03065251
eISSN
13652125
Scopus ID
2-s2.0-85129716172
Pubmed ID
35106809
Journal Title
British Journal of Clinical Pharmacology
Volume
88
Issue
7
Start Page
3272
End Page
3287
Rights Holder(s)
SCOPUS
Bibliographic Citation
British Journal of Clinical Pharmacology Vol.88 No.7 (2022) , 3272-3287
Suggested Citation
van Haren F.M.P., Laffey J.G., Artigas A., Page C., Schultz M.J., Cosgrave D., McNicholas B., Smoot T.L., Nunes Q., Richardson A., Yoon H.J., van Loon L.M., Ghosh A., Said S., Panwar R., Smith R., Santamaria J.D., Dixon B. 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. British Journal of Clinical Pharmacology Vol.88 No.7 (2022) , 3272-3287. 3287. doi:10.1111/bcp.15253 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85776
Title
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 Affiliation
University Hospital Galway
UNSW Sydney
Northern Hospital
Universitat Autònoma de Barcelona
University of Liverpool
John Hunter Hospital
Mahidol University
King's College London
The Australian National University
Nuffield Department of Medicine
University of Galway
St. Vincent's Hospital Melbourne
Amsterdam UMC - University of Amsterdam
St George Hospital
Frederick Memorial Hospital
UNSW Sydney
Northern Hospital
Universitat Autònoma de Barcelona
University of Liverpool
John Hunter Hospital
Mahidol University
King's College London
The Australian National University
Nuffield Department of Medicine
University of Galway
St. Vincent's Hospital Melbourne
Amsterdam UMC - University of Amsterdam
St George Hospital
Frederick Memorial Hospital
Other Contributor(s)
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.