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Heterogeneity of treatment effect of stress ulcer prophylaxis in ICU patients: A secondary analysis protocol
Author(s) -
Granholm Anders,
Marker Søren,
Krag Mette,
Zampieri Fernando G.,
ThorsenMeyer HansChristian,
KaasHansen Benjamin S.,
Horst Iwan C. C.,
Lange Theis,
Wetterslev Jørn,
Perner Anders,
Møller Morten H.
Publication year - 2019
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.13432
Subject(s) - medicine , subgroup analysis , pantoprazole , post hoc analysis , placebo , intensive care unit , stress ulcer , randomized controlled trial , gastrointestinal bleeding , intensive care medicine , emergency medicine , confidence interval , alternative medicine , pathology , omeprazole
Background In the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP‐ICU) trial, 3291 adult ICU patients at risk for gastrointestinal (GI) bleeding were randomly allocated to intravenous pantoprazole 40 mg or placebo once daily in the ICU. No difference was observed between the groups in the primary outcome 90‐day mortality or the secondary outcomes, except for clinically important gastrointestinal bleeding. However, heterogeneity of treatment effect (HTE) not detected by conventional subgroup analyses could be present. Methods This is a protocol and statistical analysis plan for a secondary, post hoc , exploratory analysis of the SUP‐ICU trial. We will explore HTE in one set of subgroups based on severity of illness (using the Simplified Acute Physiology Score [SAPS] II) and another set of subgroups based on the total number of risk factors for GI bleeding in each patient using Bayesian hierarchical models. We will summarise posterior probability distributions using medians and 95% credible intervals and present probabilities for different levels of benefit and harm of the intervention in each subgroup. Finally, we will assess if the treatment effect interacts with SAPS II and the number of risk factors separately on the continuous scale using marginal effects plots. Conclusions The outlined post hoc analysis will explore whether HTE was present in the SUP‐ICU trial and may help answer some of the remaining questions regarding the balance between benefits and harms of pantoprazole in ICU patients at risk of GI bleeding. ClinicalTrials.gov registration NCT02467621.