TY - JOUR

T1 - Heterogeneity of treatment effect of stress ulcer prophylaxis in ICU patients

T2 - A secondary analysis protocol

AU - Granholm, Anders

AU - Marker, Søren

AU - Krag, Mette

AU - Zampieri, Fernando G

AU - Thorsen-Meyer, Hans-Christian

AU - Kaas-Hansen, Benjamin S

AU - van der Horst, Iwan C C

AU - Lange, Theis

AU - Wetterslev, Jørn

AU - Perner, Anders

AU - Møller, Morten H

N1 - © 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1111/aas.13432

DO - 10.1111/aas.13432

M3 - Journal article

C2 - 31321771

VL - 63

SP - 1251

EP - 1256

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 9

ER -