INHALEd nebulised unfractionated HEParin for the treatment of
hospitalised patients with COVID-19 (INHALE-HEP): Protocol for an
investigator-initiated international meta-trial of randomised studies
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, assessed in a time-to-event analysis. 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.
Results of this study will be shared with the WHO, published in
scientific journals and presented at scientific meetings.