{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:17:06Z","timestamp":1788178626853,"version":"build-2803163510"},"reference-count":22,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"unspecified","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"St. Joseph\u2019s Healthcare Hamilton and McMaster University","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["201610PJT-378226-PJT-CEBA-18373"],"award-info":[{"award-number":["201610PJT-378226-PJT-CEBA-18373"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["202207CL3-492565-CTP-CEBA-19215"],"award-info":[{"award-number":["202207CL3-492565-CTP-CEBA-19215"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hamilton Academy of Health Sciences Organization","award":["HAH-22-009"],"award-info":[{"award-number":["HAH-22-009"]}]},{"name":"Physician Services Incorporated of Ontario","award":["R22-33"],"award-info":[{"award-number":["R22-33"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","award":["CPMS ID 45782"],"award-info":[{"award-number":["CPMS ID 45782"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Health and Medical Research Council of Australia","award":["GNT1124675"],"award-info":[{"award-number":["GNT1124675"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,6]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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\u2019s treatment effects differed by SARS-CoV-2 infection status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>68 intensive care units (ICUs) in eight countries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>From July 2019 to October 2023, 4821 eligible participants were enrolled in REVISE whether or not they had SARS-CoV-2 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary and secondary outcome measures<\/jats:title>\n                    <jats:p>\n                      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,\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection, patient-important upper GI bleeding, renal replacement therapy, ICU and hospital mortality and duration of mechanical ventilation, ICU and hospital stay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2014(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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      REVISE trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03374800\">NCT03374800<\/jats:ext-link>\n                      ), SARS-CoV-2 cohort study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05715567\">NCT05715567<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-119937","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:40:19Z","timestamp":1788176419000},"page":"e119937","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Proton pump inhibitors in invasively ventilated patients with SARS-CoV-2: a substudy of the re-evaluating the inhibition of stress erosions trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct03374800","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05715567","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05715567","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03374800","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05715567","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03374800","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05715567","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Brittany","family":"Dennis","sequence":"first","affiliation":[{"name":"Department of Medicine, The University of British Columbia, Vancouver, British Columbia, 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