Sample size calculation and statistical analyses
death
SECONDARY
We aimed to include 742 patients (371 in each group) to provide 90% power to detect a one-day difference in DCFDs (alpha level of 0.05, with non-parametric testing) assuming an average prevalence of 3.2 DCFDs in the control group and 4.2 in the haloperidol group (standard deviation [SD] in both groups 4.2); the estimates were based on a previous study by our group [Categorical data were presented as numbers (percentages) and continuous data as means (SD) or median (interquartile range [IQR]). Categorical data were compared using Chi-square tests or Fisher’s Exact Tests. For continuous data, independent sample t-tests or Mann Whitney-For the primary outcome, we analyzed differences between the groups with a Poisson or negative binomial mixed effects model, depending on the presence of overdispersion. We performed adjusted analyses based on significant differences in baseline characteristics between treatment groups (when present) as covariates and hospital as a random effect.For the secondary outcomes, we adjusted analyses similarly. For data with a Poisson distribution, we used a Poisson or negative binomial mixed effects model. For other continuous secondary outcomes, linear mixed effects models were used. We applied a mixed effects Cox proportional hazards model for time to ICU discharge, censoring at death, withdrawal of consent before ICU discharge, and loss to follow-up (i.e., transferred to another ICU not participating in the trial). Additionally, categorical secondary outcomes were analyzed with logistic mixed effects models. Mortality risk was assessed as a binary endpoint at 28-days after randomization. One-year mortality was expressed as time until death, calculated as time from randomization until death, and was analyzed with a mixed-effect Cox proportional model using hospital as a random effect and censoring if death had not occurred during the 1-year follow-up, if informed consent was withdrawn or if patients were lost to follow-up during the 1-year follow-up. We analyzed all data using an intention-to-treat-principle.We used SPSS (version 25) and R software (version 1.3.1073). A 