Statistical Analysis
Since this was a pilot study, no sample size or power calculations were
used; We aimed to recruit 100 patients as a pragmatic approach to
evaluate efficacy signals that could promote larger studies of nebulised
UFH for the treatment of hospitalised patients with COVID-19. As this
pilot study was not powered for definitive efficacy analysis,
significance tests were 1-sided with a 10% significance level, an
approach used in early phase clinical trials[14].
Treatment effects on survival rate were analysed by Fisher‘s exact text,
while length of stay was analysed by Wilcoxon signed ranked test. In
case of death during the study, a value of 29 days was assigned for the
number of days of hospitalization. The time to hospital discharge was
estimated by use of the Kaplan-Meier method and Hazard Ratio risk
estimates by Cox model proportional risk analysis.
The change in MOCS was analysed by
Mann-Whitney. The number of days that each subject was both oxygen free
and alive up to day 29 was determined. Fisher‘s exact text was used to
assess the effect of UFH on the requirement for mechanical ventilation.
Both primary and secondary outcomes were measured using 3 datasets, with
the ITT and mITT being the primary populations of interest:
ITT (Intention-to-treat), corresponding to all subjects who were
randomised and, for those in the active treatment group, received at
least one dose of nebulised UFH, and participated in at least one
post-baseline assessment.
A modified ITT (mITT) population which excluded (from both arms of the
ITT population) subjects admitted to ITU within 24 hrs of
randomisation and subjects who died within 24 hrs of randomisation.
Patients randomised to active treatment were required to have received
at least 4 administrations of nebulised UFH, corresponding to 24 hours
after randomisation.
PP (Per protocol), corresponding to all subjects who adhered to the
major criteria in the protocol (e.g. all subjects who completed
efficacy analyses, whose study drug compliance was between 75% and
125%), and all subjects who did not substantially deviate from the
protocol. In addition, a post hoc analysis of the sub-group of PP
patients who received at least 6 administrations of UFH was analysed;
this group was called PP6.