REVISE: re-evaluating the inhibition of stress erosions in the ICU—statistical analysis plan for a randomized trial
Diane Heels-Ansdell,
Laurent Billot,
Lehana Thabane,
Waleed Alhazzani,
Adam Deane,
Gordon Guyatt,
Simon Finfer,
François Lauzier,
John Myburgh,
Paul Young,
Yaseen Arabi,
John Marshall,
Shane English,
John Muscedere,
Marlies Ostermann,
Bala Venkatesh,
Nicole Zytaruk,
Miranda Hardie,
Naomi Hammond,
Serena Knowles,
Lois Saunders,
Alexis Poole,
Abdulrahman Al-Fares,
Feng Xie,
Richard Hall,
Deborah Cook
Affiliations
Diane Heels-Ansdell
Department of Health Research Methods Evidence and Impact, McMaster University
Laurent Billot
The George Institute for Global Health, University of New South Wales, University of New South Wales Medicine & Health
Lehana Thabane
Department of Health Research Methods Evidence and Impact, McMaster University
Waleed Alhazzani
Department of Health Research Methods Evidence and Impact, McMaster University
Adam Deane
Department of Critical Care, Melbourne Medical School, University of Melbourne
Gordon Guyatt
Department of Health Research Methods Evidence and Impact, McMaster University
Simon Finfer
Critical Care Division, The George Institute for Global Health, University of New South Wales
François Lauzier
Division of Critical Care, Department of MedicineDepartment of Anesthesiology and Critical CareFaculty of Medicine, at l`Université LavalLaval UniversityUniversite Laval Faculte de medicine
John Myburgh
Critical Care Division, The George Institute for Global Health, University of New South Wales
Paul Young
Medical Research Institute of New Zealand
Yaseen Arabi
King Saud bin Abdulaziz University for Health Sciences
John Marshall
Department of Surgery and Critical Care Medicine, Unity Health Toronto, University of Toronto
Shane English
Department of Medicine (Critical Care), Faculty of Medicine, University of Ottawa
John Muscedere
Department of Critical Care Medicine, Queens University| Kingston Health Sciences Centre
Marlies Ostermann
Department of Critical Care, King’s College London
Bala Venkatesh
The George Institute for Global Health, University of New South Wales
Nicole Zytaruk
Department of Health Research Methods Evidence and Impact, McMaster University
Miranda Hardie
The George Institute for Global Health
Naomi Hammond
University of New South Wales
Serena Knowles
The George Institute for Global Health
Lois Saunders
Academic Critical Care Office Room D176, Critical Care Medicine, St. Joseph’s Healthcare Hamilton
Alexis Poole
The University of Adelaide
Abdulrahman Al-Fares
Interdepartment Division of Critical Care Medicine, University of Toronto
Feng Xie
Department of Health Research Methods Evidence and Impact, McMaster University
Richard Hall
Dalhousie University Faculty of Medicine
Deborah Cook
Department of Health Research Methods Evidence and Impact, McMaster University
Abstract Background The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. Objective To outline the statistical analysis plan for the REVISE trial. Methods REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. Results The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. Conclusions This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. Trial registration www.ClinicalTrials.gov NCT03374800. November 21, 2017.
