{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:58:24Z","timestamp":1785376704035,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sepsis is a recognized risk factor for upper gastrointestinal bleeding, yet sepsis\u2010specific randomized evidence informing stress ulcer prophylaxis remains limited. This protocol describes\u00a0the 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\u2009mg 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\u2009days after randomization, and the primary safety outcome will be all\u2010cause mortality within 90\u2009days. Additional trial outcomes will include patient\u2010important upper gastrointestinal bleeding, ventilator\u2010associated pneumonia,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                    <\/jats:styled-content>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT03374800.\n                  <\/jats:p>","DOI":"10.1111\/aas.70267","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:05:47Z","timestamp":1779779147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pantoprazole Use in Invasively Ventilated Patients With Septic Shock: A Protocol and Statistical Analysis Plan"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-4031","authenticated-orcid":false,"given":"Akira","family":"Kuriyama","sequence":"first","affiliation":[{"name":"Department of Health Research Methods, Evidence, and Impact McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Heels\u2010Ansdell","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods, Evidence, and Impact McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon M.","family":"Fernando","sequence":"additional","affiliation":[{"name":"Department of Critical Care Lakeridge Health  Oshawa Ontario Canada"},{"name":"Department of Critical Care Medicine Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-5382","authenticated-orcid":false,"given":"Neill K. J.","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Interdepartmental Division of Critical Care Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Critical Care Medicine Sunnybrook Health Sciences Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Lamontagne","sequence":"additional","affiliation":[{"name":"Department of Critical Care University of Sherbrooke  Sherbrooke Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijan","family":"Teja","sequence":"additional","affiliation":[{"name":"Interdepartmental Division of Critical Care Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Anesthesiology and Pain Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Anesthesia, St. Michael's Hospital \u2013 Unity Health Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly Anne","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Department of Health Research Methods, Evidence &amp; Impact McMaster University  Hamilton Ontario Canada"},{"name":"St. Joseph's Healthcare Hamilton Research Institute, Division of Critical Care, St. Joseph's Healthcare Hamilton  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"Rochwerg","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Department of Health Research Methods, Evidence &amp; Impact McMaster University  Hamilton Ontario Canada"},{"name":"Knowledge Centre, Hamilton Health Sciences  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karrilloi Laiya","family":"Carayannopoulos","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Department of Critical Care St. Joseph's Healthcare Hamilton  Hamilton Ontario Canada"},{"name":"Critical Care Medicine Brantford General Hospital  Brantford Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Vazquez\u2010Grande","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Department of Critical Care St. Joseph's Healthcare Hamilton  Hamilton Ontario Canada"},{"name":"Division of Critical Care, Department of Medicine University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauralyn","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimia","family":"Honarmand","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Division of Critical Care, Department of Medicine Mackenzie Health  Vaughan Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipayan","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Department of Critical Care St. Joseph's Healthcare Hamilton  Hamilton Ontario Canada"},{"name":"Department of Critical Care Oak Valley Hospital  Markham Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Krag","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Anesthesiology, Surgery and Trauma Centre Copenhagen University Hospital  Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Zytaruk","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods, Evidence, and Impact McMaster University  Hamilton Ontario Canada"},{"name":"St. Joseph's Healthcare Hamilton Research Institute, Division of Critical Care, St. Joseph's Healthcare Hamilton  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Department of Health Research Methods, Evidence &amp; 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