Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial
- 14 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Intensive Care Medicine
- Vol. 46 (4), 717-726
- https://doi.org/10.1007/s00134-019-05903-8
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 NCT02467621Keywords
Funding Information
- Innovation Fund Denmark (4108-00011A)
- Rigshospitalet
- Capital Region of Denmark
- Scandinavian Society of Anaesthesiology and Intensive Care Medicine
- Ehrenreich’s Foundation
- Aase and Ejnar Danielsens Foundation
- Danish Society of Anaesthesiology and Intensive Care Medicine
- Danish Medical Association
- European Society of Intensive Care Medicine
- Regions of Denmark
This publication has 38 references indexed in Scilit:
- Implications of Heterogeneity of Treatment Effect for Reporting and Analysis of Randomized Trials in Critical CareAmerican Journal of Respiratory and Critical Care Medicine, 2015
- Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patientsIntensive Care Medicine, 2015
- Histamine-2 Receptor Antagonists vs Proton Pump Inhibitors on Gastrointestinal Tract Hemorrhage and Infectious Complications in the Intensive Care UnitJAMA Internal Medicine, 2014
- Reporting and handling missing values in clinical studies in intensive care unitsIntensive Care Medicine, 2013
- Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel UseAnnals of Internal Medicine, 2010
- The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studiesJournal of Clinical Epidemiology, 2008
- Seven items were identified for inclusion when reporting a Bayesian analysis of a clinical studyJournal of Clinical Epidemiology, 2005
- The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failureIntensive Care Medicine, 1996
- A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter StudyJAMA, 1993
- A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter studyJama-Journal Of The American Medical Association, 1993