Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial
Brittany B. Dennis,
Lehana Thabane,
Diane Heels-Ansdell,
Joanna C. Dionne,
Alexandra Binnie,
Jennifer Tsang,
Gordon Guyatt,
Aijaz Ahmed,
François Lauzier,
Adam Deane,
Yaseen Arabi,
John Marshall,
Nicole Zytaruk,
Lois Saunders,
Simon Finfer,
John Myburgh,
John Muscedere,
Shane English,
Marlies Ostermann,
Miranda Hardie,
Serena Knowles,
Deborah Cook,
For the REVISE Investigators the Canadian Critical Care Trials Group
Affiliations
Brittany B. Dennis
Department of Medicine, McMaster University
Lehana Thabane
Department of Health Research Methods, Evidence, and Impact, McMaster University
Diane Heels-Ansdell
Department of Health Research Methods, Evidence, and Impact, McMaster University
Joanna C. Dionne
Departments of Medicine and Health Research Methods, Evidence, and Impact, McMaster University, McMaster University Health Sciences Center
Alexandra Binnie
Department of Critical Care Medicine, Niagara Health System
Jennifer Tsang
Department of Medicine, McMaster University
Gordon Guyatt
Departments of Medicine and Health Research Methods, Evidence, and Impact, McMaster University, McMaster University Health Sciences Center
Aijaz Ahmed
Department of Gastroenterology and Hepatology, Stanford University
François Lauzier
Departments of Anesthesiology and Medicine and Critical Care Medicine, Université Laval
Adam Deane
Department of Critical Care Medicine, University of Melbourne, Melbourne Medical School
Yaseen Arabi
Intensive Care Department, Ministry of the National Guard-Health Affairs
John Marshall
Interdepartmental Division of Critical Care, University of Toronto
Nicole Zytaruk
Department of Health Research Methods, Evidence, and Impact, McMaster University
Lois Saunders
Division of Critical Care, Research Institute, St. Joseph’s Healthcare Hamilton
Simon Finfer
Critical Care Program, The George Institute for Global Health, Faculty of Medicine, University of New South Wales
John Myburgh
Critical Care Program, The George Institute for Global Health, Faculty of Medicine, University of New South Wales
John Muscedere
Department of Critical Care Medicine, Queen’s University
Shane English
Department of Medicine, University of Ottawa
Marlies Ostermann
Department of Critical Care, King’s College London
Miranda Hardie
Critical Care Program, The George Institute for Global Health, Faculty of Medicine, University of New South Wales
Serena Knowles
Critical Care Program, The George Institute for Global Health, Faculty of Medicine, University of New South Wales
Deborah Cook
Division of Critical Care, Research Institute, St. Joseph’s Healthcare Hamilton
For the REVISE Investigators the Canadian Critical Care Trials Group
Abstract Background Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection. Methods The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection. Discussion Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research. Trial registration REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].
