• Christina Cleveland Westerdahl Laursen, Troels Haxholdt Lunn, Daniel Hägi-Pedersen, Anne Sofie Nautrup Therkelsen, Claus Varnum, LangeKai Henrik WiborgKHWDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.Department of Anesthesiology, Nordsjællands Hospital, Hillerød, Denmark., Müjgan Yilmaz, Niels Anker Pedersen, Andreas Kappel, Thomas Jakobsen, Salamah Belal Eljaja, Thomas Thougaard, Ben Kristian Graungaard, Thomas Bjerno, Jacob Beck, Charlotte Runge, Joakim Steiness, Kasper Smidt Gasbjerg, Kasper Højgaard Thybo, Stig Brorson, Martin Lindberg-Larsen, Søren Overgaard, Janus Christian Jakobsen, and Ole Mathiesen.
• Centre for Anaesthesiological Research, Department of Anesthesiology, Zealand University Hospital, Køge, Denmark.
• Acta Anaesthesiol Scand. 2025 Mar 1; 69 (3): e14578e14578.

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) are recommended for pain treatment after elective hip and knee arthroplasties. However, evidence regarding the incidence of adverse effects with short-term NSAID treatment following surgery is limited. We, therefore, aim to assess the adverse effects with an eight-day postoperative treatment with ibuprofen after elective hip and knee arthroplasties.Methods And AnalysisPERISAFE is a randomized, placebo-controlled, blinded multicenter trial with 90-day and one-year follow-up. Eligible patients undergoing elective hip or knee arthroplasty are allocated 1:1 to either ibuprofen 400 mg ×3/day or identical placebo ×3/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-operation, gastrointestinal ulcer, or readmission within 90 days postoperatively. Secondary outcomes are hospital-free days within 90 days postoperatively, a composite of ibuprofen and opioid-related adverse reactions based on eight-day postoperative diary, and health related quality of life after 90 days postoperatively. 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-to-treat population.Ethics And DisseminationThe trial is approved by the Danish Medicine Agency and the Research Ethics Committee (EU CT no. 2022-502, 502-32-00). We plan to submit for publication in a major international peer-reviewed journal and present results at scientific meetings.© 2025 Acta Anaesthesiologica Scandinavica Foundation.

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