Abstract
Background Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI)
bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational
data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned
study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated
patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms
of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical
outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality,
and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole
has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes
in patients with and without COVID-19 infection.
Methods The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg
IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome
of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection
that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize
these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy
incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe
the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected
patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19
infection.