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However, evidence regarding the incidence of adverse effects with short\u2010term NSAID treatment following surgery is limited. We, therefore, aim to assess the adverse effects with an eight\u2010day postoperative treatment with ibuprofen after elective hip and knee arthroplasties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Analysis<\/jats:title><jats:p>PERISAFE is a randomized, placebo\u2010controlled, blinded multicenter trial with 90\u2010day and one\u2010year follow\u2010up. Eligible patients undergoing elective hip or knee arthroplasty are allocated 1:1 to either ibuprofen 400\u2009mg \u00d73\/day or identical placebo \u00d73\/day for eight days after surgery. The primary outcome is a composite of either death, acute myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis, renal failure, major bleeding, re\u2010operation, gastrointestinal ulcer, or readmission within 90\u2009days postoperatively. Secondary outcomes are hospital\u2010free days within 90\u2009days postoperatively, a composite of ibuprofen and opioid\u2010related adverse reactions based on eight\u2010day postoperative diary, and health related quality of life after 90\u2009days postoperatively.<\/jats:p><jats:p>A total of 2904 patients are needed to demonstrate a relative risk reduction of 33% in the placebo group, accepting a risk of type I error of 5% and type II error of 20% and a proportion of serious adverse events in the ibuprofen group of 8%. The primary analysis will be in the modified intention\u2010to\u2010treat population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and Dissemination<\/jats:title><jats:p>The trial is approved by the Danish Medicine Agency and the Research Ethics Committee (EU CT no. 2022\u2010502, 502\u201032\u201000). We plan to submit for publication in a major international peer\u2010reviewed journal and present results at scientific meetings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.14578","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T08:08:11Z","timestamp":1738224491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The adverse effects with ibuprofen after major orthopedic surgeries: A protocol for the <scp>PERISAFE<\/scp> randomized clinical trial"],"prefix":"10.1111","volume":"69","author":[{"given":"Christina Cleveland Westerdahl","family":"Laursen","sequence":"first","affiliation":[{"name":"Centre for Anaesthesiological Research, Department of Anesthesiology Zealand University Hospital  K\u00f8ge Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troels Haxholdt","family":"Lunn","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and 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