Subgroup analyses
upper GI bleeding
UPPER GI BLEEDING
We will conduct analyses of both the primary 1) Pre-hospital use of acid suppression (PPIs or H2RAs) vs. none: We hypothesize that pantoprazole is more effective at preventing clinically important upper GI bleeding among patients with 2) Illness severity measured by APACHE II score of ≥ 25 or < 25: We hypothesize no modification of the effect of pantoprazole on clinically important upper GI bleeding. We hypothesize that pantoprazole is more harmful in terms of increased risk of 90-day mortality among patients with higher versus lower illness severity, given the high illness severity subgroup finding in the SUPICU trial [3) Medical vs. surgical/trauma ICU admitting diagnosis: We hypothesize no modification of the effect of pantoprazole on preventing clinically important upper GI bleeding. We hypothesize no modification of the effect of pantoprazole on 90-day mortality.4) SARS-CoV-2 positive vs. negative status: We hypothesize no modification of the effect of pantoprazole on clinically important upper GI bleeding. We hypothesize that pantoprazole is more harmful in patients with versus without SARS-CoV-2 in terms of increased risk of 90-day mortality, given findings of prolonged course and worse outcomes of infected patients exposed to PPIs [5) Female vs. male: We hypothesize no modification of the effect of pantoprazole on clinically important upper GI bleeding. We hypothesize no modification of the effect of pantoprazole on 90-day mortality. Sex is recorded for all patients, ascertained per medical chart documentation, and will also be analyzed and reported at baseline by randomized group. The sociocultural, environmental, and behavioral factors influencing a person’s self-identity according to gender are beyond the scope of this ICU trial.We will include an interaction term between each subgroup variable and treatment group to test for subgroup effects. For any interaction 