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]