A Phase 4 interventional study of Ibuprofen and Placebo in Pain, Acute, Hip Arthropathy and Knee Arthropathy, sponsored by Naestved Hospital. Completed at 11 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-19.
Sponsored by Naestved Hospital · Phase 4, Interventional, and Treatment
Safety of an eight-day treatment with ibuprofen after primary hip and knee arthroplasties.
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:
Exclusion Criteria:
Participants received ibuprofen 400 mg tablet administered orally three times daily, with eight hour intervals, for eight days after surgery.
Drug: Ibuprofen
Participants received identical placebo tablet administered orally three times daily, with eight hour intervals, for eight days after surgery.
Drug: Placebo
400 mg tablet three times daily
tablet three times daily
A composite outcome 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.
Proportion of patients with one or more severe adverse events defined in the composite outcome 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.
Time frame: Postoperative day 0 to 90.
Hospital free days within 90 days postoperatively.
Days outside the hospital within 90 days postoperatively.
Time frame: Postoperative day 0 to 90.
A composite outcome of ibuprofen related adverse events based on an eight-day postoperative diary: dyspepsia, diarrhoea.
Proportion of patients with one or more adverse events of ibuprofen during intervention period, defined as dyspepsia or diarrhoea.
Time frame: Postoperative day 0 to 8.
A composite outcome of opioid related adverse events based on an eight-day postoperative diary: nausea, vomiting, constipation, dizziness, confusion, sedation, headache.
Proportion of patients with one or more adverse events of opioid during intervention period, defined as nausea, vomiting, constipation, dizziness, confusion, sedation, or headache.
Time frame: Postoperative day 0 to 8.
Health related quality of life questionnaire (EQ-5D-5L) after 90 days
Evaluation of health related quality of life via EuroQol five-dimensions 5 point Likert-type scale (EQ-5D-5L) questionnaire, incl. the Euro Visual analogue scales (VAS) from 0-100. 100=the best health you can imagine, 0= the worst health you can imagine. The questionnaire of health related quality of life includes: mobility, self-care, usual activities, pain or discomfort, anxiety or depression from a scale of no problems, to slight, moderate, severe problems or unable condition.
Time frame: Postoperative day 90.
Postoperative pain levels, analgesic treatment, and opioid consumption based on an eight-day postoperative diary.
Pain levels will be measured by Numeric Rating Scale (NRS) from 0-10 (no pain = 0, worst pain = 10). Analgesic treatment including opioid consumption will be indicated in total daily doses in mg.
Time frame: Postoperative day 0 to 8.
Plan to share: Yes — Data will be published anonymised according to ICMJEs (International Committee of Medical Journal Editors) guidelines
Supporting information: Study protocol, Sap
No publications or documents are linked to this record.
This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Naestved Hospital