Methods for additional analyses (e.g., subgroup analyses) {20b}
O103, diarrhea, hyperhydration, STEC, O104, HUS
SECONDARY
For additional insight, we will perform a “confirmatory” analysis restricted to patients with high-risk STEC, defined as meeting one of the following criteria:Evidence of Stx2 infectionEvidence of O157, O103, O104, O111, O113, O121, or O145 infectionBloody diarrhea and no toxin or typing availableEarly HUS and no toxin or typing availableThis is the population that would be “ideal” for the trial. However, the identification of this population prior to initiation of treatment is not feasible with current technology and workflow.The primary outcome will be analyzed across predefined subgroups to look for a differential treatment effect. Subgroups will be based on age (0 to < 5.0, 5.0 to < 10.0, and ≥ 10.0 years), sex, duration of diarrhea prior to pathway initiation (< 96 and ≥ 96 h), and baseline hematocrit (< 40% and ≥ 40%). A subgroup effect will be considered significant if the interaction between subgroup and treatment (added to the same model as used for the primary analysis) is significant at a Bonferroni-corrected level. Exploratory outcomes will be analyzed in the same way as the primary and secondary outcomes with no adjustment for multiple comparisons. When these results are reported, they will be identified as exploratory.Safety analyses: frequencies of SAEs will be compared between subjects allocated to hyperhydration vs. those allocated to conservative fluid management. The occurrence of any SAE will be considered as a dichotomous outcome. The start date, stop date, severity, relationship, expectedness, outcome, and duration of SAEs will be reported and treatment-associated SAEs will be presented in a table or listing.