Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial

Summary

Patients who are critically ill in the in the Intensive Care Unit (ICU), especially those who need a breathing machine, can develop ulcers in the stomach that bleed. To prevent bleeding, many such patients around the world receive a drug called pantoprazole that decreases acid production. However, today, compared to decades ago, critically ill patients rarely develop upper gastrointestinal bleeding. This decrease is likely due to modern medicine, better resuscitation and earlier feeding. There may also be harms associated with pantoprazole and other drugs that reduce acid levels in the stomach including lung infections (pneumonia) and bowel infections (Clostridioides difficile). Studies in this area are old and of modest quality. Therefore, it is difficult to know whether pantoprazole does decrease stomach bleeding these days, or whether the possible harms of lung and bowel infections are actually more common and more serious problems. The goal of this international study is to determine if, in critically ill patients using breathing machines, the use of pantoprazole is effective in preventing bleeding from stomach ulcers or whether it causes more problems such as lung infection (pneumonia) and bowel infection (Clostridioides difficile), or whether pantoprazole has no effect at all. Whether the harms are worth the benefits, and whether the benefits are worth the costs, will be determined by an economic analysis to inform patients, families, clinicians, and healthcare systems globally.

Timeline

Start

2018-07-09

Primary completion

2023-10-31

Completion

2024-01-31

Publications

• Kuriyama A, Heels-Ansdell D, Fernando SM, Adhikari NKJ, Lamontagne F, Teja B, Lewis KA, Rochwerg B, Carayannopoulos KL, Vazquez-Grande G, McIntyre L, Honarmand K, Chaudhuri D, Krag M, Zytaruk N, Cook D; Canadian Critical Care Trials Group. Pantoprazole Use in Invasively Ventilated Patients With Septic Shock: A Protocol and Statistical Analysis Plan. Acta Anaesthesiol Scand. 2026 Jul;70(6):e70267. doi: 10.1111/aas.70267.
• Humphries B, Zytaruk N, Heels-Ansdell D, Lau V, Rochwerg B, Fowler R, Yao Y, Cook DJ, Xie F. Protocol for an economic evaluation alongside the Re-Evaluating the Inhibition of Stress Erosions (E-REVISE) trial. BMJ Open. 2025 Nov 9;15(11):e106841. doi: 10.1136/bmjopen-2025-106841.
• Clarke F, Hand L, Deane A, Zytaruk N, Hardie M, Arabi Y, Al-Fares A, Heels-Ansdell D, Dechert W, Ostermann M, Watpool I, Millen T, Muscedere J, English S, Boyd G, Sibley S, Peck L, Eastwood G, Duan E, Soth M, Freitag A, Vazquez-Grande G, Slessarev M, Ball I, Geagea A, Burns K, Binnie A, Mehta S, Tsang J, Burry L, D'Aragon F, Cook D. Coenrollment in a critical care trial: Characteristics and consequences. Contemp Clin Trials. 2025 Jul;154:107938. doi: 10.1016/j.cct.2025.107938. Epub 2025 May 14.
• Cook D, Deane A, Lauzier F, Zytaruk N, Guyatt G, Saunders L, Hardie M, Heels-Ansdell D, Alhazzani W, Marshall J, Muscedere J, Myburgh J, English S, Arabi YM, Ostermann M, Knowles S, Hammond N, Byrne KM, Chapman M, Venkatesh B, Young P, Rajbhandari D, Poole A, Al-Fares A, Reis G, Johnson D, Iqbal M, Hall R, Meade M, Hand L, Duan E, Clarke F, Dionne JC, Tsang JLY, Rochwerg B, Karachi T, Lamontagne F, D'Aragon F, St Arnaud C, Reeve B, Geagea A, Niven D, Vazquez-Grande G, Zarychanski R, Ovakim D, Wood G, Burns KEA, Goffi A, Wilcox ME, Henderson W, Forrest D, Fowler R, Adhikari NKJ, Ball I, Mele T, Binnie A, Trop S, Mehta S, Morgan I, Loubani O, Vanstone M, Fiest K, Charbonney E, Cavayas YA, Archambault P, Rewa OG, Lau V, Kristof AS, Khwaja K, Williamson D, Kanji S, Sy E, Dennis B, Reynolds S, Marquis F, Lellouche F, Rahman A, Hosek P, Barletta JF, Cirrone R, Tutschka M, Xie F, Billot L, Thabane L, Finfer S; REVISE Investigators. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med. 2024 Jul 4;391(1):9-20. doi: 10.1056/NEJMoa2404245. Epub 2024 Jun 14.
• Heels-Ansdell D, Billot L, Thabane L, Alhazzani W, Deane A, Guyatt G, Finfer S, Lauzier F, Myburgh J, Young P, Arabi Y, Marshall J, English S, Muscedere J, Ostermann M, Venkatesh B, Zytaruk N, Hardie M, Hammond N, Knowles S, Saunders L, Poole A, Al-Fares A, Xie F, Hall R, Cook D. 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.
• Deane AM, Alhazzani W, Guyatt G, Finfer S, Marshall JC, Myburgh J, Zytaruk N, Hardie M, Saunders L, Knowles S, Lauzier F, Chapman MJ, English S, Muscedere J, Arabi Y, Ostermann M, Venkatesh B, Young P, Thabane L, Billot L, Heels-Ansdell D, Al-Fares AA, Hammond NE, Hall R, Rajbhandari D, Poole A, Johnson D, Iqbal M, Reis G, Xie F, Cook DJ; Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. REVISE: Re-Evaluating the Inhibition of Stress Erosions in the ICU: a randomised trial protocol. BMJ Open. 2023 Nov 15;13(11):e075588. doi: 10.1136/bmjopen-2023-075588.
• Dennis BB, Thabane L, Heels-Ansdell D, Dionne JC, Binnie A, Tsang J, Guyatt G, Ahmed A, Lauzier F, Deane A, Arabi Y, Marshall J, Zytaruk N, Saunders L, Finfer S, Myburgh J, Muscedere J, English S, Ostermann M, Hardie M, Knowles S, Cook D; REVISE Investigators the Canadian Critical Care Trials Group. 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. Trials. 2023 Aug 30;24(1):561. doi: 10.1186/s13063-023-07589-2.

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