• Qianyu Zhuang, Liyuan Tao, Jin Lin, Jin Jin, Wenwei Qian, Yanyan Bian, Yulong Li, Yulei Dong, Huiming Peng, Ye Li, Yu Fan, Wei Wang, Bin Feng, Na Gao, Tiezheng Sun, Jianhao Lin, Miaofeng Zhang, Shigui Yan, Bin Shen, Fuxing Pei, and Xisheng Weng.
• Department of Orthopedics, Peking Union Medical College Hospital, Beijing, China.
• BMJ Open. 2020 Jan 9; 10 (1): e030501.

ObjectivesTo evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety.DesignDouble-blind, pragmatic, randomised, placebo-controlled trial.SettingFour tertiary hospitals in China.Participants246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA).InterventionsPatients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions.Primary And Secondary Outcome MeasuresThe primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption.ResultsThe cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group.ConclusionsThe sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA.Trial Registration NumberClinicalTrials.gov (ID: NCT02198924).© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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