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.