Introduction
INHALE-HEP is a prospective collaborative individual participant data
meta-analysis of randomised controlled trials and early phase studies,
to determine whether treatment with nebulised unfractionated heparin
(UFH) improves relevant outcomes in hospitalised COVID-19 patients who
do not require immediate mechanical ventilation. Individual studies take
place in multiple countries.
INHALE-HEP is registered on ClinicalTrials.gov (NCT04545541). The full
details of our trial methodology are published in a separate manuscript
in this journal. [REFERENCE BJCP]
We previously outlined the scientific rationale and current pre-clinical
and clinical evidence for the use of nebulised UFH as a treatment for
COVID-19 in a comprehensive review article.[1] In addition to the
well-known anti-inflammatory and anticoagulant effects, UFH has proven
anti-viral activity against SARS-CoV-2.[2] In a pre-pandemic
double-blind randomised study in 256 critically ill ventilated patients,
nebulised UFH limited progression of lung injury and accelerated return
to home in survivors.[3]
Here we describe the pre-specified statistical analysis plan developed
by the study executive committee and trial statisticians before
completion of patient recruitment and data collection. Our statistical
analysis plan outlines the principles and methods of analysing and
reporting the trial results. The use of a pre-specified plan is
recommended to reduce the risk of analysis bias arising from knowledge
of the trial results emerging during the conduct of the analyses.[4,
5] This statistical analysis plan has been prepared in accordance with
published guidelines for the content of statistical analysis plans in
clinical trials (Appendix).[5]