Abstract
Introduction
Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential for COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus’ entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis.
Methods and intervention
This meta-trial is a prospective collaborative individual patient data meta-analysis of randomised controlled trials and early phase studies. Individual studies are conducted in multiple countries. Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, are randomised to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have specific outcome measures in addition to the core set.
Ethics and dissemination: The meta-trial is registered at ClinicalTrials.gov, ID NCT04635241. The Brazilian study protocol was approved by the Institute of Biomedical Sciences (ICB) Ethics Committee, Sao Paulo (ID 38660320.0.0000.5467). The Argentinian study protocol was approved by the Independent Ethics Committee for Clinical Pharmacology Trials, Buenos Aires (ID N 3183). The Egyptian study protocol was approved by the Ethics committee, Faculty of Medicine, Alexandria University (ID 2158_11456_4737). Each contributing study is also registered individually as follows: PACTR202007606032743 (Egypt), NCT04530578 (Argentina). Registration and ethics approval are pending in other countries. Results of this study will be shared with the WHO, published in scientific journals and presented at scientific meetings.