Renal Adverse Events Associated With Ibuprofen Treatment After Hip and Knee Arthroplasties—A Protocol for the Preplanned Substudy of the PERISAFE Trial

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for postoperative pain management after hip and knee arthroplasties but have been associated with renal adverse effects. The risk may increase when NSAIDs are combined with diuretics and angiotensin converting enzyme (ACE) inhibitors or Angiotensin-II-receptor antagonists. The aim of this substudy is to assess potential renal adverse effects of an eight-day postoperative treatment with ibuprofen in patients undergoing hip or knee arthroplasty during 90-days follow-up. Methods and Analysis: This substudy is part of the PERISAFE trial—a randomized, placebo-controlled, blinded multicenter trial including 2904 patients undergoing hip or knee arthroplasty. Patients are randomized to receive either ibuprofen 400 mg three times daily or identical placebo three times daily for 8 days postoperatively. The primary outcome is the number of patients with renal dysfunction according to RIFLE criteria Level 1–5, at any point during the 90-day follow-up. The substudy is powered at 86.3% to detect or discard a 40% relative risk reduction in the placebo group, assuming an incidence of acute renal injury of 6.2%. Ethics and Dissemination: The ethical approval for this substudy is included in the main PERISAFE trial, which has been approved by the Danish Medicine Agency, the National Committee on Health Research Ethics (EU CT no. 2022-502502-32-00), and the Danish Data Protection Agency (REG-149-2022).