Re-evaluating the Inhibition of Stress Erosions (REVISE): A protocol for pilot randomized controlled trial

INTRODUCTION: Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increase infections. Therefore, a large randomized clinical trial (RCT) is needed to inform modern practice. The aim of this multicenter pilot trial is to determine the feasibility of performing a large RCT to investigate the efficacy and safety of withholding intravenous pantoprazole. METHODS AND ANALYSIS: We will include adult critically ill patients who have an anticipated duration of ventilation of =48 hours. We will exclude patients with acute or recent GI bleeding, pregnancy, dual antiplatelet therapy, poor prognosis or intent to withdraw life support, or previous enrolment in this or a confounding trial. Following informed consent, patients will be randomized to receive the intervention of placebo (0.9% NaCl) or intravenous pantoprazole 40 mg daily. Patients, families, clinicians, data collectors, adjudicators of outcome and statisticians will be blind to allocation. The three primary feasibility outcomes are the informed consent rate, recruitment rate, and protocol adherence. Clinical outcomes include clinically important upper GI bleeding, ventilator-associated pneumonia (VAP), Clostridium difficile infection, length of stay and mortality in ICU and hospital. ETHICS AND APPROVAL: This study has been approved by Health Canada, and research ethics board (REB) at each of the participating centers. TRIAL REGISTRATION NUMBER: This trial was registered on 31 October 2014. The trial registration number is NCT02290327. FUNDING: REVISE Pilot Trial is funded by Research Grant awarded by Physicians Services Incorporated, Dammam University Research Funds, Capital Health Authority Research Award Halifax, and Royal Adelaide Hospital Project Committee Grant.