Secondary outcomes
Secondary outcomes will be analysed with the same analyses as described for the primary outcome.
Subgroup analyses
We plan to undertake subgroup analyses of the following variables: severity of COVID-19 (according to the PaO2/FiO2 ratio and the modified ordinal scale), duration of intervention, time from admission to start of intervention, time from development of symptoms to start of intervention, administration of other therapies, age and sex of the patients.
Safety outcomes and adverse events
Adverse events are categorised as “not related”, “unlikely”, “possibly”, “probably” or “definitely related” to treatment, as determined by site investigators. Events will be tabulated by treatment group and reported as frequency counts (n) and proportions (%).
Future analyses
Individual studies contributing to the meta-trial may be analysed and published separately as per the original protocols of these studies. We will consider conducting hypothesis-generating exploratory analyses other than those pre-specified above to further evaluate the impact of nebulised heparin on outcomes in this dataset. Any such analyses conducted after knowing the main results of the INHALE-HEP meta-trial will be cautiously interpreted and clearly indicated in any subsequent publications.