{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:15:29Z","timestamp":1790702129382,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CLASSIC trial is an investigator\u2010initiated, international, randomised, stratified, and analyst\u2010blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health\u2010related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre\u2010defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention\u2010to\u2010treat (ITT) population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The CLASSIC trial results will provide important evidence to guide clinicians\u2019 choice regarding the IV fluid therapy in adults with septic shock.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.13434","type":"journal-article","created":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T13:08:45Z","timestamp":1562332125000},"page":"1262-1271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial\u2014Protocol and statistical analysis plan"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-1596","authenticated-orcid":false,"given":"Tine 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