NCT05575700

Safety of Ibuprofen After Major Orthopaedic Surgeries

Safety of Ibuprofen After Major Orthopaedic Surgeries. The PERISAFE Randomized Clinical Multicentre Trial

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 2,904 (actual)
• Sponsor: Naestved Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Safety of an eight-day treatment with ibuprofen after primary hip and knee arthroplasties.

Detailed description

Hip and knee arthroplasty surgeries are some of the most frequently performed planned procedures in the western world. Multimodal analgesic treatment is the leading analgesic treatment principle, with NSAIDs as an essential part. Ibuprofen, the most frequently prescribed NSAID, is effective in reducing acute postoperative pain. However, ibuprofen may be associated with various serious adverse events, including death, cardiovascular morbidity, gastrointestinal ulcer, and renal impairment. The balance between beneficial and harmful effects of a short-term postoperative treatment with ibuprofen after elective hip and knee arthroplasty is unknown. Objectives: to assess the adverse events of an eight-day treatment of postoperative pain with ibuprofen in patients undergoing elective primary hip or knee arthroplasty. Intervention: the participants will be randomized in two groups: a) oral ibuprofen 400 mg 3 times daily for eight days. b) identical oral placebo 3 times daily for eight days. Design and trial size: PERISAFE is a randomized, placebo-controlled multicentre trial with centralized computer-generated allocation sequence and allocation concealment with unknown block size. Patients, investigators, assessors, caregivers, data-managers, writers of the manuscript, and statisticians will be blinded. A total of 2904 eligible patients are needed to detect or discard an effect corresponding to a relative risk reduction of 1/3 with an acceptable risk of type I error of 5 % and of type II error of 20 %, and a proportion of the composite outcome of serious adverse events of 8% in the experimental group. Sub-studies: * Serious adverse events relating to the renal system * Serious adverse events relating to the cardiovascular system * Serious adverse events relating to the gastrointestinal system, including major bleeding * Persistent pain and opioid consumption at 90 days and one year postoperatively. Predictive co-factors include preoperative analgesic treatment, type of anesthesia, gender, age, ASA-classification, diabetes, and type of surgery * Bayesian re-analysis of the primary and secondary outcomes up to 90 days postoperatively. Further details will appear in the statistical analysis plan * Health-related quality of life via EQ-5D-5L questionnaire 90-days and one year postoperatively

Conditions

• Pain, Acute
• Hip Arthropathy
• Knee Arthropathy
• Safety Issues
• Analgesia
• Analgesic Adverse Reaction
• Postoperative Pain
• Postoperative Complications

Interventions

Type	Name	Description
DRUG	Ibuprofen	400 mg tablet three times daily
DRUG	Placebo	tablet three times daily

Timeline

• Start date: 2023-04-17
• Primary completion: 2025-08-19
• Completion: 2025-08-19
• First posted: 2022-10-12
• Last updated: 2025-12-19

Locations

11 sites across 1 country: Denmark