The Adverse Effects Associated With Ibuprofen Use After Major Orthopaedic Surgeries—A Detailed Statistical Analysis Plan for the <scp>PERISAFE</scp> Randomized Clinical Trial

The PERISAFE trial aims to assess the adverse effects associated with an 8-day postoperative treatment with ibuprofen after hip and knee arthroplasties. This paper outlines the detailed statistical analysis plan for the primary data. The PERISAFE trial is a randomized, placebo-controlled, blinded multicentre trial allocating 2904 hip- or knee-arthroplasty patients 1:1 to ibuprofen 400 mg ×3/day or identical placebo ×3/day for 8 days postoperatively. The primary outcome is a composite of 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 outcomes are hospital-free days within 90 days postoperatively, a composite of ibuprofen and opioid-related adverse reactions based on an 8-day postoperative diary, and health-related quality of life after 90 days postoperatively. All randomized patients who undergo surgery will be included in all analyzes. Binary data will be analyzed using a mixed-effects generalized linear model, count data will be analyzed using the van Elteren test, and continuous data will be analyzed using a mixed-effects linear regression. Additionally, the win ratio will be calculated for the primary outcome. The statistical analyzes will be conducted in accordance with this pre-planned statistical analysis plan with one interim analysis after the inclusion of 1400 patients. All analyzes will be adjusted for site. We expect that the PERISAFE trial will provide high-quality data based on predefined detailed methodology regarding the safety of postoperative treatment with ibuprofen after elective hip and knee arthroplasties.

Authors

Institutions

Publication Details

Journal
Acta Anaesthesiologica Scandinavica
Published
2025-05-28
DOI
https://doi.org/10.1111/aas.70062
Citations
1
Primary Topic
Inflammatory mediators and NSAID effects
Type
article
Field-Weighted Citation Impact
1.39

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The Adverse Effects Associated With Ibuprofen Use After Major Orthopaedic Surgeries—A Detailed Statistical Analysis Plan for the PERISAFE Randomized Clinical Trial

Ben Kristian Graungaard, Søren Overgaard, Charlotte Runge, Niels Anker Pedersen et al.
1 citations
Acta Anaesthesiologica Scandinavica
Inflammatory mediators and NSAID effects
1.39
article

The Adverse Effects Associated With Ibuprofen Use After Major Orthopaedic Surgeries—A Detailed Statistical Analysis Plan for the PERISAFE Randomized Clinical Trial

Ben Kristian Graungaard, Søren Overgaard, Charlotte Runge, Niels Anker Pedersen, Kai Henrik Wiborg Lange, Janus Christian Jakobsen, Claus Varnum, Kasper Højgaard Thybo, Troels Haxholdt Lunn, Ole Mathiesen, Markus Harboe Olsen, Joakim Steiness, Daniel Hägi‐Pedersen, Kasper Smidt Gasbjerg, Christina Cleveland Westerdahl Laursen, Martin Lindberg‐Larsen, Müjgan Yilmaz, Andreas Kappel, Stig Brorson, Thomas Thougaard, Anne Sofie Nautrup Therkelsen, Salamah Belal Eljaja, Thomas Bjerno, Peter Birk Hollænder, Thomas Jakobsen
article en
1 citations

Abstract

The PERISAFE trial aims to assess the adverse effects associated with an 8-day postoperative treatment with ibuprofen after hip and knee arthroplasties. This paper outlines the detailed statistical analysis plan for the primary data. The PERISAFE trial is a randomized, placebo-controlled, blinded multicentre trial allocating 2904 hip- or knee-arthroplasty patients 1:1 to ibuprofen 400 mg ×3/day or identical placebo ×3/day for 8 days postoperatively. The primary outcome is a composite of 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 outcomes are hospital-free days within 90 days postoperatively, a composite of ibuprofen and opioid-related adverse reactions based on an 8-day postoperative diary, and health-related quality of life after 90 days postoperatively. All randomized patients who undergo surgery will be included in all analyzes. Binary data will be analyzed using a mixed-effects generalized linear model, count data will be analyzed using the van Elteren test, and continuous data will be analyzed using a mixed-effects linear regression. Additionally, the win ratio will be calculated for the primary outcome. The statistical analyzes will be conducted in accordance with this pre-planned statistical analysis plan with one interim analysis after the inclusion of 1400 patients. All analyzes will be adjusted for site. We expect that the PERISAFE trial will provide high-quality data based on predefined detailed methodology regarding the safety of postoperative treatment with ibuprofen after elective hip and knee arthroplasties.

Acta Anaesthesiologica ScandinavicaVol. 69(6)
University of Copenhagen (DK), University of Southern Denmark (DK), Aalborg University Hospital (DK), Frederiksberg Hospital (DK), Odense University Hospital (DK), Copenhagen University Hospital (DK), Gentofte Hospital (DK), Rigshospitalet (DK), Nordsjællands Hospital (DK), Regionshospitalet Silkeborg (DK), Ringsted Sygehus (DK), Lillebaelt Hospital (DK), Zealand University Hospital Køge (DK)
Danmarks Frie Forskningsfond, Lægeforeningen, Skibsreder Per Henriksen, R. og hustrus fond, Region Sjælland
Good health and well-being
Openalex Percentile: Top 20%
Inflammatory mediators and NSAID effects
1.39
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.