Clinical trial NCT05575700: Safety of Ibuprofen After Major Orthopaedic Surgeries
Official title: Safety of Ibuprofen After Major Orthopaedic Surgeries. The PERISAFE Randomized Clinical Multicentre Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pain, Acute
Hip Arthropathy
Knee Arthropathy
Safety Issues
Analgesia
Analgesic Adverse Reaction
Postoperative Pain
Postoperative Complications
Keywords: PERISAFE
Hip Arthroplasty
Knee Arthroplasty
Postoperative pain
Analgesia
Safety
Non-steroidal Anti-inflammatory drugs
Lead sponsor: Naestved Hospital
Sponsor class: OTHER
First posted: 2022-10-12
Enrollment: 2904
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

* One-year follow-up on the composite primary outcome.
* Subgroup analysis on predictors of chronic pain and opioid consumption at 90-days, and one-year after surgery.
* Coherence of preoperative use of diuretics, ACE-inhibitors or Angiotensin-II-antagonists and postoperative risk of renal failure.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Postoperative day 0 to 90.
Secondary outcomes:
measure: Hospital free days within 90 days postoperatively.
timeFrame: Postoperative day 0 to 90.
measure: A composite outcome of ibuprofen related adverse events based on an eight-day postoperative diary: dyspepsia, diarrhoea.
timeFrame: Postoperative day 0 to 8.
measure: A composite outcome of opioid related adverse events based on an eight-day postoperative diary: nausea, vomiting, constipation, dizziness, confusion, sedation, headache.
timeFrame: Postoperative day 0 to 8.
measure: Health related quality of life questionnaire (EQ-5D-5L) after 90 days
timeFrame: Postoperative day 90.
Other outcomes:
measure: Proportion of individual serious adverse events in the composite primary outcome.
timeFrame: Postoperative day 0 to 90.
measure: Proportion of individual adverse events of ibuprofen and opioid in the composite secondary outcomes.
timeFrame: Postoperative day 0 to 8.
measure: Postoperative pain levels, analgesic treatment, and opioid consumption based on an eight-day postoperative diary.
timeFrame: Postoperative day 0 to 8.
Locations:
city: Brøndby
country: Denmark
facility: Private Hospital Gildhøj
city: Copenhagen NV
country: Denmark
facility: Bispebjerg Hospital
city: Farsø
country: Denmark
facility: Aalborg University Hospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital Hillerød
city: Køge
country: Denmark
facility: Zealand University Hospital
city: Næstved
country: Denmark
facility: Næstved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Silkeborg
country: Denmark
facility: Silkeborg Regional Hospital
city: Svendborg
country: Denmark
facility: Svendborg Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
Study officials:
affiliation: Zealand University Hospital
name: Ole Mathiesen, Professor
role: STUDY_CHAIR
References: