Home›Emergency Medicine› Pantoprazole Benefits COVID-19 ICU Patients Without Raising Mortality
Pantoprazole Benefits COVID-19 ICU Patients Without Raising MortalityTrial shows pantoprazole helps prevent gastrointestinal bleeding in COVID patients
BMJ openPublished September 2, 2026Study authors: Dennis Brittany, Heels-Ansdell Diane, Ibrahim Quazi, Basmaji John, Thabane Lehana, Guyatt Gordon, Sa…PubMed ↗NCT03374800 ↗DOI ↗Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic
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Key Takeaway
Pantoprazole safely reduces GI bleeding in COVID-19 ICU patients, but infection itself worsens mortality and recovery.
This pre-planned substudy of the REVISE trial analyzed 532 mechanically ventilated ICU patients across 68 units in eight countries. Researchers compared outcomes between those with and without SARS-CoV-2 infection, all of whom received pantoprazole or placebo for stress ulcer prophylaxis.
SARS-CoV-2 infection was not linked to clinically important upper gastrointestinal bleeding (adjusted HR 0.78, 95% CI 0.40-1.50). However, infected patients had significantly higher ICU, hospital, and 90-day mortality, as well as longer durations of mechanical ventilation, ICU stay, and hospital stay.
The effect of pantoprazole on reducing clinically important upper GI bleeding and on 90-day mortality was consistent regardless of SARS-CoV-2 status. This suggests that the drug's benefits and risks are similar in COVID-19 and non-COVID-19 critically ill patients.
These findings support the use of pantoprazole for stress ulcer prophylaxis in this population, as it reduces bleeding without adversely affecting survival or other key outcomes. The study's randomized design and international scope strengthen its conclusions, though it was not specifically powered for subgroup analyses.
Clinicians can be reassured that pantoprazole is effective and safe in COVID-19 ICU patients, but the overall worse prognosis in infected patients underscores the need for continued vigilance and management of the underlying infection.
How this fits prior evidence
How this fits prior evidence: This finding addresses a gap regarding the safety and efficacy of proton pump inhibitors in critically ill patients with specific viral infections. While previous coverage noted that pantoprazole exposure was linked to insulin autoimmune syndrome in a case report, this study confirms that pantoprazole remains a consistent intervention for reducing clinically important upper gastrointestinal bleeding regardless of SARS-CoV-2 status.
Researchers conducted a study involving 532 critically ill patients who were on ventilators. The study looked at how the medication pantoprazole affected patients with COVID-19, specifically focusing on whether it could prevent serious upper gastrointestinal bleeding and impact mortality rates.
The results showed that having a COVID-19 infection was not linked to an increased risk of gastrointestinal bleeding. However, patients with COVID-19 did experience higher rates of mortality and longer stays in the intensive care unit and hospital. Importantly, the study found that pantoprazole worked consistently to reduce serious stomach bleeding regardless of whether the patient had COVID-19 or not.
This study was a pre-planned substudy of a larger trial. While the results suggest pantoprazole is effective at managing bleeding in these patients, the findings are specific to this clinical setting. Patients and doctors should discuss these results with a medical professional to determine the best treatment plan for specific cases.
What this means for you:
Pantoprazole was found to reduce serious stomach bleeding in critically ill patients with COVID-19.
Common questions
Does pantoprazole help patients with COVID-19?
The study found that pantoprazole reduced clinically important upper gastrointestinal bleeding in patients with COVID-19. The medication's effect on bleeding was consistent regardless of whether the patient had a COVID-19 infection or not.
Are there risks to using pantoprazole in these patients?
The study did not report any specific adverse events or safety concerns regarding the use of pantoprazole in patients with COVID-19. It was found to be effective for preventing bleeding without negatively affecting other outcomes.
How did COVID-19 affect the patients in this study?
Patients with COVID-19 in the study were associated with significantly higher ICU, hospital, and 90-day mortality. These patients also experienced longer durations of mechanical ventilation and longer stays in both the intensive care unit and the hospital.
OBJECTIVES: Observational studies suggest that acid suppression may worsen outcomes among patients infected with SARS-CoV-2. The objectives of this embedded substudy of a randomised controlled trial evaluating pantoprazole in mechanically ventilated patients were to (1) describe the clinical characteristics of critically ill patients with SARS-CoV-2, (2) compare clinical outcomes with a propensity-matched non-infected cohort and (3) assess whether pantoprazole's treatment effects differed by SARS-CoV-2 infection status.
DESIGN: A pre-planned substudy of the re-evaluating the inhibition of stress erosions (REVISE) trial, including a propensity-matched analysis of infected and non-infected patients comparing the effect of pantoprazole between patients with and without SARS-CoV-2.
SETTING: 68 intensive care units (ICUs) in eight countries.
PARTICIPANTS: From July 2019 to October 2023, 4821 eligible participants were enrolled in REVISE whether or not they had SARS-CoV-2 infection.
PRIMARY AND SECONDARY OUTCOME MEASURES: Participants enrolled in REVISE with SARS-CoV-2 infection had additional data collection, including biomarkers, venous thromboembolism, SARS-CoV-2 therapies and tracheostomy timing. The primary outcomes were clinically important upper gastrointestinal bleeding and 90-day mortality. Secondary outcomes included ventilator-associated pneumonia, infection, patient-important upper GI bleeding, renal replacement therapy, ICU and hospital mortality and duration of mechanical ventilation, ICU and hospital stay.
RESULTS: Of the eligible trial cohort, 11.9% (540/4550) had SARS-CoV-2; 532 patients had additional SARS-CoV-2-specific data collection. Of these 532 patients, 87.8% received COVID-19-directed treatments-(dexamethasone 75.2%), 11.7% developed pulmonary embolism and 9.2% developed deep-vein thrombosis. After propensity matching, SARS-CoV-2 infection was not associated with clinically important upper gastrointestinal bleeding (adjusted HR 0.78, 95% CI 0.40 to 1.50) but was associated with significantly higher ICU, hospital and 90-day mortality, as well as longer duration of ventilation and ICU and hospital length of stay. The effect of pantoprazole on clinically important upper GI bleeding and 90-day mortality was consistent regardless of SARS-CoV-2 status.
CONCLUSIONS: SARS-CoV-2 infection was associated with higher mortality and longer duration of mechanical ventilation, ICU and hospital stays, without an increased risk of clinically important upper gastrointestinal bleeding. Pantoprazole reduced clinically important upper gastrointestinal bleeding without adversely affecting other outcomes.
TRIAL REGISTRATION NUMBER: REVISE trial (NCT03374800), SARS-CoV-2 cohort study (NCT05715567).
