Statistical analysis
SECONDARY, REGRESSIONS
We split analyses between CRA (main analyses) and RBAA (secondary analyses). All analyses were intention-to-treat.Baseline characteristics and adherence to the strategy were described in each group (strategy vs. control), and compared by using the absolute value of the standardized difference (Stdiff), with a Stdiff > 0.1 considered as a marker of imbalance between groups. We described categorical variables with frequencies and percentages, and continuous variables with mean and standard deviation (SD) in case of normal distribution, or median and interquartile range (IQR) otherwise.We described outcomes in each group (strategy vs. control) with frequencies and percentages for categorical variables, median and IQR for continuous variables, or Kaplan Meier estimates for survival.To assess the effect of the strategy, we used log-binomial mixed models (or modified Poisson regressions in case of non-convergence) for binary outcomes, and zero-inflated negative binomial (or zero-inflated Poisson) mixed models for continuous outcomes. We relied on two-level crude models, with ICU (and 2-month period effect in RBAA only) entered as a random effect and intervention group as a fixed effect. As planned, we entered additional unbalanced baseline characteristics (age, SAPS II, and McCabe score) as fixed effects in adjusted models. We presented the results as exp(parameters) with their 95% confidence intervals (CIs). For binary outcomes analyzed with log-binomial or modified Poisson mixed models, exp(parameters) can be interpreted as risk-ratios [RRs]. For continuous outcomes analyzed with zero-inflated models, exp(parameters) can be interpreted as odds ratios (OR) for the logistic zero-excess part of the model and as a multiplicative factor of the counting process for the negative binomial part of the model.We imputed missing outcomes based on the maximal bias hypothesis. In multivariable analyses, we treated missing unbalanced baseline characteristics by multiple imputation. Assuming an expected 60-day mortality of 37.5% [We monitored data for all included patients while the trial was ongoing (list of queries available upon request).The POINCARE-2 trial was registered at ClinicalTrials.gov (NCT 02,765,009).