REVISE: R e- Ev aluating the I nhibition of S tress E rosions in the ICU: a randomised trial protocol

Adam M Deane; Waleed Alhazzani; Gordon Guyatt; Simon Finfer; John C Marshall; John Myburgh; Nicole Zytaruk; Miranda Hardie; Lois Saunders; Serena Knowles; Francois Lauzier; Marianne J Chapman; Shane English; John Muscedere; Yaseen Arabi; Marlies Ostermann; Balasubramanian Venkatesh; Paul Young; Lehana Thabane; Laurent Billot; Diane Heels-Ansdell; Abdulrahman A Al-Fares; Naomi E Hammond; R Hall; Dorrilyn Rajbhandari; Alexis Poole; Daniel Johnson; Mobeen Iqbal; Gilmar Reis; Feng Xie; Deborah J Cook; Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group

doi:10.1136/bmjopen-2023-075588

REVISE: R e- Ev aluating the I nhibition of S tress E rosions in the ICU: a randomised trial protocol

BMJ Open. 2023 Nov 15;13(11):e075588. doi: 10.1136/bmjopen-2023-075588.

Authors

Adam M Deane¹, Waleed Alhazzani², Gordon Guyatt³, Simon Finfer⁴, John C Marshall⁵, John Myburgh⁴, Nicole Zytaruk³, Miranda Hardie⁴, Lois Saunders⁶, Serena Knowles⁴, Francois Lauzier⁷, Marianne J Chapman⁸, Shane English^{9

10}, John Muscedere¹¹, Yaseen Arabi¹², Marlies Ostermann¹³, Balasubramanian Venkatesh¹⁴, Paul Young¹⁵, Lehana Thabane³, Laurent Billot¹⁶, Diane Heels-Ansdell³, Abdulrahman A Al-Fares¹⁷, Naomi E Hammond¹⁸, R Hall¹⁹, Dorrilyn Rajbhandari¹⁸, Alexis Poole⁸, Daniel Johnson²⁰, Mobeen Iqbal²¹, Gilmar Reis²², Feng Xie³, Deborah J Cook²³; Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group

Affiliations

¹ Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia.
² Departments of Medicine and Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada.
³ Department of Health Research Methods, Evidence & Impact, Mcmaster University, Hamilton, Ontario, Canada.
⁴ Critical Care Program, The George Institute for Global Health, Sydney, New South Wales, Australia.
⁵ Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada.
⁶ Research Institute, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
⁷ Departments of Anesthesiology, Medicine & Critical Care Medicine, Centre de Recherche du CHU de Québec - Université Laval, Laval, Quebec, Canada.
⁸ Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
⁹ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
¹⁰ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹¹ Department of Critical Care Medicine, Queens University, Kingston, Ontario, Canada.
¹² Intensive Care Department, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
¹³ Department of Critical Care, King's College London, Guy's & St Thomas' Hospital, London, UK.
¹⁴ Critical Care Program, The George Institute for Global Health, Newtown, New South Wales, Australia.
¹⁵ Intensive Care Department, Wellington Hospital, London, UK.
¹⁶ Statistics Division, The George Institute for Global Health, Newtown, New South Wales, Australia.
¹⁷ Departments of Anesthesia, Critical Care Medicine and Pain Medicine, Al-Amiri Hospital, Kuwait City, Kuwait.
¹⁸ Critical Care Medicine, The George Institute for Global Health, Newtown, New South Wales, Australia.
¹⁹ Departments of Anesthesia, Critical Care and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
²⁰ Departments of Critical Care and Anesthesia, University of Nebraska Medical Center, Omaha, Nebraska, USA.
²¹ Intensive Care Department, Maroof International Hospital, Islamabad, Pakistan.
²² Cardresearch-Cardiologia Assistencial e de Pesquisa LTDA, Pontifical Catholic University of Minas Gerais, Belo Horizonte, Brazil.
²³ Departments of Medicine and Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada [email protected].

Abstract

Introduction: The Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.

Methods and analysis: REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of 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 level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.

Ethics and dissemination: All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to - Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.

Trial registration number: NCT03374800.

Keywords: Adult gastroenterology; Adult intensive & critical care; Bleeding disorders & coagulopathies; Clinical Trial; Gastroduodenal disease.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Gastrointestinal Hemorrhage / therapy
Humans
Intensive Care Units
Pantoprazole
Pneumonia, Ventilator-Associated*
Proton Pump Inhibitors* / therapeutic use
Randomized Controlled Trials as Topic
Respiration, Artificial

Substances

Pantoprazole
Proton Pump Inhibitors

Associated data

ClinicalTrials.gov/NCT03374800

Grants and funding

CPMS ID 45782/DH_/Department of Health/United Kingdom