Protocole changes
SECONDARY
Day 28 mortality was measured, as a post hoc analysis of our data since day 28 mortality was not listed as a prespecified outcome in our trial.As additional immune parameters, three unspecified exploratory outcomes were added to the trial and were evaluated on day 1, day 3, and day 7: number of circulating monocytic myeloid-derived suppressor cells (M-MDSCs), which was evaluated only in one center (Rennes); total lymphocyte count; and indoleamine-pyrrole 2,3-dioxygenase (IDO) activity.During the peer review process, changes have been made to the statistical analysis plan. A sensitivity analysis on the primary endpoint has been added: an Analysis of Covariance (ANCOVA) adjusting for the SOFA score at day 1 was used to analyze SOFA score at day 7. For secondary endpoint, a log transformation was applied to deal with non-normal distribution of the following variables: arginine, citrulline, glutamine, ornithine, and kynurenine.