Abstract
Introduction
Inhaled nebulised unfractionated heparin (UFH) has a strong scientific
and biological rationale that warrants urgent investigation of its
therapeutic potential in patients with 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
The INHALE d nebulised unfractionated HEP arin for the
treatment of hospitalised patients with COVID-19 (INHALE-HEP) meta-trial
is a prospective individual patient data analysis of on-going randomised
controlled trials and early phase studies. Individual studies are being
conducted in multiple countries. Participating studies randomise adult
patients admitted to the hospital with confirmed SARS-CoV-2 infection,
who do not require immediate mechanical ventilation, to inhaled
nebulised UFH or standard care. All studies collect a minimum core
dataset. The primary outcome for the meta-trial 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 additional outcomes.
Analysis
We use a Bayesian approach to monitoring, followed by analysing
individual patient data, outcomes and adverse events. All analyses will
follow the intention-to-treat principle, considering all participants in
the treatment group to which they were assigned, except for cases lost
to follow-up or withdrawn.
Trial registration, ethics and dissemination
The meta-trial is registered at ClinicalTrials.gov ID NCT04635241. Each
contributing study is individually registered and has received approval
of the relevant ethics committee or institutional review board. Results
of this study will be shared with the WHO, published in scientific
journals and presented at scientific meetings.