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:
1,073 studies on the registry are indexed under Acute Pain; 166 are open to participants now.
This study's enrollment of 2,904 is above the median of 86 across 902 interventional studies indexed under Acute Pain.
Browse Acute Pain studies →Naestved Hospital is the lead sponsor of 29 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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, Statistical analysis plan
Time frame: Nine month after the trial has ended, and the primary results article has been published The study protocol and statistical analysis plan will be available after they have been published. Study protocol will be available at PERISAFE website.
Access criteria: We will make anonymized data available to other researchers' trough public database such as Zenodo open data repository (CERN), or another equivalent database. Furthermore, researchers wishing to access data from the PERISAFE trial should contact omat@regionsjaelland.dk in the first instance.
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This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ibuprofen
Naestved Hospital