DataSheet2_Efficacy and safety of intravenous acetaminophen (2 g/day) for reducing opioid consumption in Chinese adults after elective orthopedic surgery: A multicenter randomized controlled trial.docx

Background: Acetaminophen is an important component of a multimodal analgesia strategy to reduce opioid consumption and pain intensity after an orthopedic surgery. The opioid-sparing efficacy of intravenous acetaminophen has been established at a daily dose of 4 g. However, it is still unclear for the daily dose of 2 g of acetaminophen, which is recommended by the China Food and Drug Administration Center for Drug Evaluation, in terms of its efficacy and safety.
Objectives: This study aimed to evaluate the efficacy and safety of intravenous acetaminophen at a daily dose of 2 g for reducing opioid consumption and pain intensity after orthopedic surgery.
Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, 235 patients who underwent orthopedic surgery were randomly assigned to receive intravenous acetaminophen 500 mg every 6 h or placebo. Postoperative morphine consumption, pain intensity at rest and during movement, and adverse events were analysed.
Results: For the mean (standard deviation) morphine consumption within 24 h after surgery, intravenous acetaminophen was superior to placebo both in the modified intention-to-treat analysis [8.7 (7.7) mg vs. 11.2 (9.2) mg] in the acetaminophen group and the placebo group, respectively. Difference in means: 2.5 mg; 95% confidence interval, 0.25 to 4.61; p = 0.030), and in the per-protocol analysis (8.3 (7.0) mg and 11.7 (9.9) mg in the acetaminophen group and the placebo group, respectively. Difference in means: 3.4 mg; 95% confidence interval: 1.05 to 5.77; p = 0.005). The two groups did not differ significantly in terms of pain intensity and adverse events.
Conclusion: Our results suggest that intravenous acetaminophen at a daily dose of 2 g can reduce morphine consumption by Chinese adults within the first 24 h after orthopedic surgery, but the extent of reduction is not clinically relevant.
Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02811991].

背景：对乙酰氨基酚（acetaminophen）是多模式镇痛方案的重要组成部分，可降低骨科手术后的阿片类药物消耗量与疼痛强度。静脉用对乙酰氨基酚的阿片类药物节俭效应在每日剂量4g时已得到证实，但中国国家药品监督管理局药品审评中心（China Food and Drug Administration Center for Drug Evaluation）推荐的每日2g剂量的对乙酰氨基酚，其有效性与安全性仍未明确。
研究目的：本研究旨在评估每日剂量2g的静脉用对乙酰氨基酚，用于降低骨科手术后阿片类药物消耗量与疼痛强度的有效性与安全性。
研究方法：本项多中心、随机、双盲、安慰剂对照Ⅲ期临床试验共纳入235例行骨科手术的患者，将其随机分配至每6小时静脉给予对乙酰氨基酚500mg组或安慰剂组。本研究对术后吗啡消耗量、静息及活动状态下的疼痛强度与不良事件进行了分析。
研究结果：术后24小时内的吗啡消耗量（均值±标准差）方面，在改良意向治疗分析中，静脉用对乙酰氨基酚组的吗啡消耗量为8.7（7.7）mg，安慰剂组为11.2（9.2）mg，对乙酰氨基酚组优于安慰剂组，组间均值差为2.5mg，95%置信区间0.25~4.61，p=0.030；在符合方案集分析中，对乙酰氨基酚组与安慰剂组的吗啡消耗量分别为8.3（7.0）mg与11.7（9.9）mg，组间均值差为3.4mg，95%置信区间1.05~5.77，p=0.005。两组在疼痛强度与不良事件发生率方面无显著差异。
研究结论：本研究结果显示，每日剂量2g的静脉用对乙酰氨基酚可降低中国骨科手术患者术后24小时内的吗啡消耗量，但该降低幅度未达到临床意义。
临床试验注册：[ClinicalTrials.gov]，注册号[NCT02811991]。