Protocol of the Can Nebulised Heparin Reduce Time to Extubation in SARS-CoV-2 (CHARTER) Study

Introduction COVID-19 is associated with the development of ARDS displaying the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. The anti-coagulant actions of nebulised heparin limit fibrin deposition and progression of lung injury. Serendipitously, unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents its entry into mammalian cells. Nebulisation of heparin may therefore limit both fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. For these reasons we have initiated a multi-centre international trial of nebulised heparin in patients with COVID-19. Methods and intervention Mechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2 infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant on chest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours or standard care for up to 10 days while mechanically ventilated. The primary outcome is the time to separation from invasive ventilation to day 28, where non-survivors to day 28 are treated as though not separated from invasive ventilation. Ethics and dissemination The study protocol has been submitted to the human research and ethics committee of St Vincent’s Hospital, Melbourne, Australia. Submission is pending in other jurisdictions. Results of this study will be published in scientific journals and presented at scientific meetings. Trial Registration ACTRN: 12620000517976 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ACTRN: 12620000517976 ### Funding Statement No external funding was received ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data can be obtained by contacting the chief investigator