塞来昔布-曲马多共晶在伴有截骨术的拇囊炎切除术后中重度疼痛患者中的应用：一项 3 期、随机、双盲、析因、阳性药物和安慰剂对照的临床试验。
Celecoxib-tramadol co-crystal in patients with moderate-to-severe pain following bunionectomy with osteotomy: A phase 3, randomized, double-blind, factorial, active- and placebo-controlled trial.
机构信息
Department of Anesthesiology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Department of Anesthesiology, University of Buffalo/Roswell Park Cancer Institute, Buffalo, New York, USA.
出版信息
Pain Pract. 2023 Jan;23(1):8-22. doi: 10.1111/papr.13136. Epub 2022 Jul 8.
BACKGROUND
Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly.
AIM
We evaluated CTC in moderate-to-severe acute postoperative pain.
MATERIALS AND METHODS
This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48 h sum of pain intensity differences (SPID0-48) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals.
RESULTS
In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0-48 (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; p < 0.001), celecoxib (-103.7 [-116.4, -91.0]; p < 0.001), or placebo (-74.6 [-92.5, -56.6]; p < 0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths.
CONCLUSION
CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.
背景
塞来昔布-曲马多共晶（CTC）是塞来昔布和消旋曲马多的首类镇痛共晶药物，与单独/同时给予其活性成分相比，其共晶结构赋予了改善的药理特征。
目的
我们评估了 CTC 在中度至重度急性术后疼痛中的作用。
材料和方法
这是一项在美国 6 家临床研究中心进行的随机、双盲、析因、阳性药物和安慰剂对照的 3 期试验（NCT03108482）。接受截骨术的拇囊炎患者在手术后出现中度至重度急性疼痛，随机分为口服 CTC（200 mg [112 mg 塞来昔布/88 mg 消旋曲马多盐酸盐]每 12 小时一次）、曲马多（50 mg 每 6 小时一次）、塞来昔布（100 mg 每 12 小时一次）或安慰剂，持续 48 小时。患者、研究者和医务人员对分组均不知情。主要终点是所有随机患者的 0-48 小时疼痛强度差值总和（SPID0-48）。疼痛强度使用 0-10 数字评分量表（NRS）进行评估。接受研究药物治疗的患者进行安全性分析。由 ESTEVE 制药公司资助。
结果
在 2017 年（3 月至 11 月），共有 1323 名患者接受了筛选，其中 637 名患者被随机分配至 CTC（n=184）、曲马多（n=183）、塞来昔布（n=181）或安慰剂（n=89）组。所有活性药物组的基线 NRS 平均为 6.7。与曲马多（-109.1 [-121.7, -96.4]；p<0.001）、塞来昔布（-103.7 [-116.4, -91.0]；p<0.001）或安慰剂（-74.6 [-92.5, -56.6]；p<0.001）相比，CTC 对 SPID0-48 的影响明显更大（最小二乘均值：-139.1 [95%置信区间：-151.8, -126.5]）。CTC 组共有 358 例患者发生治疗中出现的不良事件（TEAE），而曲马多组有 394 例。CTC 组有 37.7%的患者发生药物相关的 TEAEs，而曲马多组有 48.6%。两组均无严重 TEAEs/死亡事件。
结论
与相当剂量的曲马多和塞来昔布相比，CTC 提供了更强的镇痛效果，且与曲马多相比具有相似的耐受性。CTC 已在美国获批上市。
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