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01.04.2020 | Original

Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial

verfasst von: Anders Granholm, Søren Marker, Mette Krag, Fernando G. Zampieri, Hans-Christian Thorsen-Meyer, Benjamin Skov Kaas-Hansen, Iwan C. C. van der Horst, Theis Lange, Jørn Wetterslev, Anders Perner, Morten Hylander Møller

Erschienen in: Intensive Care Medicine | Ausgabe 4/2020

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Abstract

Purpose

The Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial compared prophylactic pantoprazole with placebo in 3291 adult ICU patients at risk of clinically important gastrointestinal bleeding (CIB). As a predefined subgroup analysis suggested increased 90-day mortality with pantoprazole in the most severely ill patients, we aimed to further explore whether heterogenous treatment effects (HTE) were present.

Methods

We assessed HTE in subgroups defined according to illness severity by SAPS II quintiles and the total number of risk factors for CIB using Bayesian hierarchical models, and on the continuous scale using Bayesian logistic regression models with interactions. Estimates were presented as posterior probability distributions of odds ratios (ORs), probabilities of different effect sizes, and marginal effects plots.

Results

We observed potential HTE for 90-day mortality according to illness severity (median subgroup OR range 0.90–1.09) with higher risk in the most severely ill, but not with different numbers of risk factors (1.00–1.02). We observed potential HTE of pantoprazole for clinically important events (0.86–1.18) and infectious adverse events (0.88–1.27) with higher risk in patients with greater illness severity and in those with more risk factors for CIB. Pantoprazole substantially and consistently reduced the risk of CIB with no indications of HTE (0.53–0.63).

Conclusions

In this post hoc analysis of the SUP-ICU trial, we found indications of HTE with increased risks of serious adverse events in patients with greater illness severity or more risk factors for CIB allocated to pantoprazole. These findings are hypothesis-generating and warrant further prospective investigation.

ClinicalTrials.gov identifier

NCT02467621

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Titel: Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial
verfasst von: Anders Granholm
Søren Marker
Mette Krag
Fernando G. Zampieri
Hans-Christian Thorsen-Meyer
Benjamin Skov Kaas-Hansen
Iwan C. C. van der Horst
Theis Lange
Jørn Wetterslev
Anders Perner
Morten Hylander Møller
Publikationsdatum: 01.04.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Intensive Care Medicine / Ausgabe 4/2020
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-019-05903-8

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Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial