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

doi:10.1186/s13063-023-07794-z

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial

Trials. 2023 Dec 6;24(1):796. doi: 10.1186/s13063-023-07794-z.

Authors

Diane Heels-Ansdell¹, Laurent Billot², Lehana Thabane¹, Waleed Alhazzani¹, Adam Deane³, Gordon Guyatt¹, Simon Finfer⁴, François Lauzier⁵, John Myburgh⁴, Paul Young⁶, Yaseen Arabi⁷, John Marshall⁸, Shane English⁹, John Muscedere¹⁰, Marlies Ostermann¹¹, Bala Venkatesh¹², Nicole Zytaruk^{1

13}, Miranda Hardie¹⁴, Naomi Hammond¹⁵, Serena Knowles¹⁴, Lois Saunders¹³, Alexis Poole¹⁶, Abdulrahman Al-Fares¹⁷, Feng Xie¹, Richard Hall¹⁸, Deborah Cook^{19

20

21}

Affiliations

¹ Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
² The George Institute for Global Health, University of New South Wales, University of New South Wales Medicine & Health, Sydney, New South Wales, Australia.
³ Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, Australia.
⁴ Critical Care Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Division of Critical Care, Department of MedicineDepartment of Anesthesiology and Critical CareFaculty of Medicine, at l`Université LavalLaval UniversityUniversite Laval Faculte de medicine, Quebec, Canada.
⁶ Medical Research Institute of New Zealand, Wellington, New Zealand.
⁷ King Saud bin Abdulaziz University for Health Sciences, Riyad, Saudi Arabia.
⁸ Department of Surgery and Critical Care Medicine, Unity Health Toronto, University of Toronto, Toronto, Canada.
⁹ Department of Medicine (Critical Care), Faculty of Medicine, University of Ottawa, Ottawa, Canada.
¹⁰ Department of Critical Care Medicine, Queens University| Kingston Health Sciences Centre, Kingston, Ontario, Canada.
¹¹ Department of Critical Care, King's College London, London, UK.
¹² The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
¹³ Academic Critical Care Office Room D176, Critical Care Medicine, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada.
¹⁴ The George Institute for Global Health, Newton, Australia.
¹⁵ University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ The University of Adelaide, Adelaide, Australia.
¹⁷ Interdepartment Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
¹⁸ Dalhousie University Faculty of Medicine, Halifax, Canada.
¹⁹ Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada. debcook@mcmaster.ca.
²⁰ Academic Critical Care Office Room D176, Critical Care Medicine, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada. debcook@mcmaster.ca.
²¹ Department of Medicine, McMaster University, Hamilton, ON, Canada. debcook@mcmaster.ca.

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.

Keywords: Clostridioides difficile infection; Critically ill; Gastrointestinal bleeding; Stress ulceration; Ventilator-associated pneumonia.

Publication types

Randomized Controlled Trial

MeSH terms

Adolescent
Adult
Critical Illness
Gastrointestinal Hemorrhage / drug therapy
Gastrointestinal Hemorrhage / therapy
Humans
Intensive Care Units*
Pantoprazole / adverse effects
Pneumonia, Ventilator-Associated* / drug therapy
Proton Pump Inhibitors / adverse effects
Respiration, Artificial

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial

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