Safety of Ibuprofen After Major Orthopaedic Surgeries

Postoperative Pain Clinical Trial

— PERISAFE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05575700
• Other study ID #: 001CCWL2022
• Status: Recruiting
• Phase: Phase 4
• Start date: April 17, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2023
• Source: Naestved Hospital
• Contact: Daniel Hägi-Pedersen, Assoc. Prof
• Phone: +45 21517167
• Email: dhag[@]regionsjaelland.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2904
• Est. completion date: December 31, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ibuprofen
400 mg tablet three times daily
• Placebo
tablet three times daily

Locations

Country	Name	City	State
Denmark	Private Hospital Gildhøj	Brøndby
Denmark	Bispebjerg Hospital	Copenhagen NV
Denmark	Aalborg University Hospital	Farsø
Denmark	Gentofte Hospital	Hellerup
Denmark	Nordsjællands Hospital Hillerød	Hillerød
Denmark	Zealand University Hospital	Køge
Denmark	Næstved Hospital	Næstved
Denmark	Odense University Hospital	Odense
Denmark	Silkeborg Regional Hospital	Silkeborg
Denmark	Svendborg Hospital	Svendborg
Denmark	Vejle Sygehus	Vejle

Sponsors (1)

Lead Sponsor	Collaborator
Naestved Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of individual serious adverse events in the composite primary outcome.	Proportion of individual elements of the primary composite outcome: death, acute myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis, renal failure, major bleeding, re-operation, gastrointestinal ulcer, or readmission.	Postoperative day 0 to 90.
Other	Proportion of individual adverse events of ibuprofen and opioid in the composite secondary outcomes.	Proportion of individual elements of secondary outcome of adverse events of ibuprofen and opioid: dyspepsia, diarrhoea, nausea, vomiting, constipation, dizziness, confusion, sedation, headache.	Postoperative day 0 to 8.
Other	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.	Postoperative day 0 to 8.
Primary	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.	Postoperative day 0 to 90.
Secondary	Hospital free days within 90 days postoperatively.	Days outside the hospital within 90 days postoperatively.	Postoperative day 0 to 90.
Secondary	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.	Postoperative day 0 to 8.
Secondary	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.	Postoperative day 0 to 8.
Secondary	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.	Postoperative day 90.