Optimal Research LLC, Austin, TX, USA.
AFT Pharmaceuticals Ltd, Auckland, New Zealand.
Clin Ther. 2019 Oct;41(10):1982-1995.e8. doi: 10.1016/j.clinthera.2019.07.008. Epub 2019 Aug 22.
Multimodal analgesia with acetaminophen and/or nonsteroidal anti-inflammatory drugs is recommended for the treatment of postoperative pain. Although oral fixed-dose combinations (FDCs) are available, parenteral administration may be clinically justified. The goal of this study was to investigate the clinical efficacy and safety of an intravenous FDC of ibuprofen and acetaminophen after bunionectomy.
This study was a prospective, randomized, double-blind, multicenter, placebo-controlled factorial clinical trial conducted at 2 clinical research centers in the United States between November 2016 and June 2017. Eligible patients (male and female subjects, aged 18-65 years, reporting pain intensity levels ≥40 mm on a 100-mm visual analog scale (VAS) after distal, first metatarsal bunionectomy) were randomized (3:3:3:2) to receive the FDC (ibuprofen 300 mg + acetaminophen 1000 mg), ibuprofen 300 mg, acetaminophen 1000 mg, or placebo (vehicle), administered as 15-minute intravenous infusions every 6 hours for 48 hours. The primary efficacy end point was the time-adjusted sum of pain intensity differences from baseline over 48 hours (SPID). In addition to VAS pain intensity scores, pain relief scores, time to perceptible and meaningful pain relief, the use of rescue medication, and participant's global evaluations of the study drug were recorded. Adverse events occurring during the 48-hour treatment period were included in the safety analysis.
A total of 276 participants were enrolled; most were female (82%), the mean age was 42.4 years, and the median baseline VAS was 67 mm, indicating moderate to severe pain. SPID was significantly higher for the FDC (23.4 [2.5] mm) than for ibuprofen (9.5 [2.5] mm), acetaminophen (10.4 [2.5] mm), and placebo (-1.3 [3.1] mm; all, P < 0.001). The superior analgesic effect of the FDC was supported by a range of secondary end points, including reduced opioid usage rates (75% for FDC, 92% for ibuprofen, 93% for acetaminophen, and 96% for placebo; all, P < 0.005). The safety profile of the FDC was comparable to that of intravenous ibuprofen or acetaminophen alone. Three participants withdrew from the study due to adverse events: 2 in the ibuprofen group and 1 in the acetaminophen group.
The study found that repeated administration of an intravenous FDC of ibuprofen and acetaminophen provided statistically significant improvement in SPID over comparable doses of either monotherapy without an increase in adverse events. ClinicalTrials.gov identifier: NCT02689063.
对于术后疼痛，推荐使用对乙酰氨基酚和/或非甾体抗炎药的多模式镇痛。尽管有口服固定剂量复方制剂（FDC），但临床可能有理由采用注射剂。本研究的目的是研究氟比洛芬酯和对乙酰氨基酚静脉 FDC 在拇囊炎切除术后的临床疗效和安全性。
这是一项在美国 2 家临床研究中心进行的前瞻性、随机、双盲、多中心、安慰剂对照析因临床试验。入选患者（18-65 岁的男性和女性受试者，在接受第一跖骨远端拇囊炎切除术报告疼痛强度水平≥40mm 的 100mm 视觉模拟量表[VAS]后）按 3:3:3:2 比例随机（3:3:3:2）接受 FDC（布洛芬 300mg+对乙酰氨基酚 1000mg）、布洛芬 300mg、对乙酰氨基酚 1000mg 或安慰剂（载体）治疗，均以 15 分钟静脉输注，每 6 小时一次，共 48 小时。主要疗效终点为 48 小时内时间调整的疼痛强度差值总和（SPID）。除 VAS 疼痛强度评分外，还记录疼痛缓解评分、感知到有意义的疼痛缓解时间、补救药物的使用情况以及参与者对研究药物的总体评价。包括在 48 小时治疗期间发生的不良事件。
共纳入 276 名参与者；大多数为女性（82%），平均年龄为 42.4 岁，中位数基线 VAS 为 67mm，表明疼痛为中度至重度。FDC 的 SPID 明显高于布洛芬（23.4[2.5]mm）、对乙酰氨基酚（10.4[2.5]mm）和安慰剂（-1.3[3.1]mm；均 P<0.001）。FDC 的优越镇痛效果得到了一系列次要终点的支持，包括降低阿片类药物使用率（FDC 为 75%，布洛芬为 92%，对乙酰氨基酚为 93%，安慰剂为 96%；均 P<0.005）。FDC 的安全性与单独使用静脉内布洛芬或对乙酰氨基酚相似。3 名参与者因不良事件退出研究：布洛芬组 2 名，对乙酰氨基酚组 1 名。
研究发现，重复给予氟比洛芬酯和对乙酰氨基酚静脉 FDC 可显著改善 SPID，优于等效剂量的单一疗法，且不增加不良事件。临床试验.gov 标识符：NCT02689063。
