Analgesia, Analgesic Adverse Reaction, Hip Arthropathy, Knee Arthropathy, Pain, Acute, Postoperative Complications, Postoperative Pain, Safety Issues
Conditions
Keywords
PERISAFE, Hip Arthroplasty, Knee Arthroplasty, Postoperative pain, Analgesia, Safety, Non-steroidal Anti-inflammatory drugs
Brief 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
Interventions
DRUGIbuprofen
400 mg tablet three times daily
DRUGPlacebo
tablet three times daily
Sponsors
Naestved Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study medication will be masked by the pharmacy. The experimental medicine will be packed and labelled by Region Hovedstadens Pharmacy in accordance with the Good Manufacturing Practice regulations. The sponsor has a set of sealed, opaque envelopes with the participants' allocation, and these will only be revealed for the investigators when the data has been analysed and abstracts and conclusions covering the different possibilities for interpreting the trial results, have been agreed upon by the steering committee
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients scheduled for elective primary hip and knee arthroplasty. * Age ≥ 18 years. * Planned postoperative treatment with NSAID. * Negative pregnancy test for women in the fertile age. * Informed consent.
Exclusion criteria
* Unable to understand or speak Danish. * Allergy to or contraindications against ibuprofen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Postoperative day 0 to 90. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital free days within 90 days postoperatively. | Postoperative day 0 to 90. | Days outside the hospital within 90 days postoperatively. |
| A composite outcome of ibuprofen related adverse events based on an eight-day postoperative diary: dyspepsia, diarrhoea. | Postoperative day 0 to 8. | Proportion of patients with one or more adverse events of ibuprofen during intervention period, defined as dyspepsia or diarrhoea. |
| A composite outcome of opioid related adverse events based on an eight-day postoperative diary: nausea, vomiting, constipation, dizziness, confusion, sedation, headache. | Postoperative day 0 to 8. | Proportion of patients with one or more adverse events of opioid during intervention period, defined as nausea, vomiting, constipation, dizziness, confusion, sedation, or headache. |
| Health related quality of life questionnaire (EQ-5D-5L) after 90 days | Postoperative day 90. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain levels, analgesic treatment, and opioid consumption based on an eight-day postoperative diary. | Postoperative day 0 to 8. | 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. |
Countries
Denmark
Outcome results
None listed