Pantoprazole Use in Invasively Ventilated Patients With Septic Shock: A Protocol and Statistical Analysis Plan.

Abstract

Sepsis is a recognized risk factor for upper gastrointestinal bleeding, yet sepsis-specific randomized evidence informing stress ulcer prophylaxis remains limited. This protocol describes the rationale, methods, and statistical analysis plan for a post hoc subgroup analysis evaluating pantoprazole versus placebo in invasively ventilated critically ill adults with septic shock enrolled in the REVISE trial (NCT03374800). This study will be a post hoc extended subgroup analysis of the international, blinded, randomized REVISE trial, which enrolled 4821 mechanically ventilated adults in 68 ICUs across 8 countries. Patients were randomized to intravenous pantoprazole 40 mg once daily or placebo during invasive mechanical ventilation. Septic shock will be defined as receipt of vasopressors or inotropes at baseline together with an admitting diagnosis of infection according to APACHE III diagnostic categories. The primary efficacy outcome will be clinically important upper gastrointestinal bleeding in the ICU within 90 days after randomization, and the primary safety outcome will be all-cause mortality within 90 days. Additional trial outcomes will include patient-important upper gastrointestinal bleeding, ventilator-associated pneumonia, Clostridioides difficile infection during hospitalization, new renal replacement therapy, mortality in the ICU and hospital, and duration of ICU and hospital stay. Analyses will be adjusted for prehospital acid suppression; the mortality analyses will be additionally adjusted for APACHE II score. This protocol and statistical analysis plan describes an evaluation of the efficacy and safety of pantoprazole in patients with septic shock within a large randomized trial dataset. Trial Registration: ClinicalTrials.gov identifier: NCT03374800.