Laursen Christina C W, Lunn Troels H, Hägi-Pedersen Daniel, Olsen Markus Harboe, Kappel Andreas, Jakobsen Thomas, Pedersen Niels A, Thougaard Thomas, Graungaard Ben K, Bjerno Thomas, Hollænder Peter B, Runge Charlotte, Yilmaz Müjgan, Eljaja Salamah B, Therkelsen Anne S N, Steiness Joakim, Gasbjerg Kasper S, Thybo Kasper, Lange Kai H W, Brorson Stig, Varnum Claus, Lindberg-Larsen Martin, Overgaard Søren, Mathiesen Ole, Jakobsen Janus C
Centre for Anaesthesiological Research, Department of Anaesthesiology, Zealand University Hospital, Køge, Denmark.
Department of Anaesthesia and Intensive Care, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
Acta Anaesthesiol Scand. 2025 Jul;69(6):e70062. doi: 10.1111/aas.70062.
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.
PERISAFE试验旨在评估髋膝关节置换术后使用布洛芬进行8天术后治疗的相关不良反应。本文概述了主要数据的详细统计分析计划。PERISAFE试验是一项随机、安慰剂对照、双盲多中心试验，将2904例髋或膝关节置换患者按1:1随机分配，术后8天每天服用3次400毫克布洛芬或相同的安慰剂。主要结局是术后90天内死亡、急性心肌梗死、中风、肺栓塞、深静脉血栓形成、肾衰竭、大出血、再次手术、胃肠道溃疡或再次入院的复合情况。次要结局是术后90天内无住院天数、基于术后8天日记的布洛芬和阿片类药物相关不良反应的复合情况，以及术后90天后的健康相关生活质量。所有接受手术的随机分组患者都将纳入所有分析。二元数据将使用混合效应广义线性模型进行分析，计数数据将使用范埃尔特伦检验进行分析，连续数据将使用混合效应线性回归进行分析。此外，将计算主要结局的胜率。统计分析将按照这个预先计划的统计分析计划进行，在纳入1400例患者后进行一次中期分析。所有分析都将针对研究地点进行调整。我们预计，PERISAFE试验将基于关于择期髋膝关节置换术后使用布洛芬进行术后治疗安全性的预定义详细方法提供高质量数据。
