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.
Frank M P van HarenJohn Gerard LaffeyAntonio ArtigasClive PageMarcus J SchultzDavid CosgraveBairbre McNicholasThomas L SmootQuentin NunesAlice RichardsonHwan-Jin YoonLex M van LoonAngajendra GhoshSimone SaidRakshit PanwarRoger SmithJohn D SantamariaBarry Dixonnull nullPublished in: British journal of clinical pharmacology (2022)
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.
Keyphrases
- respiratory failure
- clinical trial
- phase iii
- study protocol
- mechanical ventilation
- open label
- phase ii
- venous thromboembolism
- extracorporeal membrane oxygenation
- placebo controlled
- growth factor
- sars cov
- double blind
- randomized controlled trial
- intensive care unit
- anti inflammatory
- phase ii study
- coronavirus disease
- healthcare
- cardiovascular events
- palliative care
- squamous cell carcinoma
- newly diagnosed
- pulmonary embolism
- risk assessment
- cardiac surgery
- electronic health record
- big data
- chronic kidney disease
- community acquired pneumonia