Singla Neil K, Pollak Richard, Gottlieb Ira, Leiman David, Minkowitz Harold, Zimmerman John, Harnett Mark, Ryan Michael, Lu Lucy, Reines Scott
Lotus Clinical Research, Pasadena, CA, USA.
Evolution Research Group, New Providence, NJ, USA.
Pain Ther. 2020 Dec;9(2):545-562. doi: 10.1007/s40122-020-00184-2. Epub 2020 Jul 18.
This study is part of the registrational program for intravenously administered (IV) tramadol in the USA and compared the analgesic benefit and tolerability of two doses of IV tramadol (50 mg and 25 mg) to placebo in adult patients undergoing bunionectomy, an orthopedic surgical model.
This was a phase 3, multicenter, double-blind, three-arm, randomized, placebo-controlled, multiple-dose, parallel-group trial to evaluate IV tramadol in the management of postoperative pain following bunionectomy. Eligible patients were randomized (1:1:1 ratio) to IV tramadol 50 mg, 25 mg, or placebo. Primary endpoint was summary of pain intensity differences over 48 h (SPID48). Key secondary endpoints included SPID24, total consumption of rescue analgesia, and patient global assessment of efficacy (PGA). Safety assessments included treatment emergent adverse events (TEAEs), clinical laboratory tests, vital signs, and electrocardiograms (ECGs). Assessment of the dose-response was an important objective of the study.
The study established a dose response, with IV tramadol 50 mg demonstrating statistically significant benefit (p < 0.05) over placebo for primary and all key secondary efficacy endpoints, whereas tramadol 25 mg demonstrated intermediate results between the 50 mg and placebo arms. IV tramadol 50 mg was well tolerated; most common TEAEs were nausea and vomiting; and there were no meaningful differences among treatments for vital signs, ECG, and laboratory assessments. The largest proportion of patients completed tramadol 50 mg (98.6%) compared to tramadol 25 mg (91.8%) and placebo (88.2%).
IV tramadol 50 mg was effective and well tolerated as treatment for postoperative pain following bunionectomy surgery, while IV tramadol 25 mg, although well tolerated, was judged an ineffective dose for the treatment of pain in this setting. IV tramadol 50 mg was further developed in the registrational program for the USA.
ClinicalTrials.gov identifier, NCT03290378.
本研究是美国静脉注射曲马多注册项目的一部分，比较了两剂静脉注射曲马多（50毫克和25毫克）与安慰剂对接受拇囊炎切除术的成年患者（一种骨科手术模型）的镇痛效果和耐受性。
这是一项3期、多中心、双盲、三臂、随机、安慰剂对照、多剂量、平行组试验，旨在评估静脉注射曲马多在拇囊炎切除术后疼痛管理中的作用。符合条件的患者按1:1:1比例随机分为静脉注射50毫克曲马多组、25毫克曲马多组或安慰剂组。主要终点是48小时内疼痛强度差异的总和（SPID48）。关键次要终点包括SPID24、急救镇痛药的总消耗量以及患者对疗效的总体评估（PGA）。安全性评估包括治疗中出现的不良事件（TEAE）、临床实验室检查、生命体征和心电图（ECG）。评估剂量反应是该研究的一个重要目标。
该研究确立了剂量反应关系，50毫克静脉注射曲马多在主要和所有关键次要疗效终点上显示出比安慰剂有统计学显著益处（p < 0.05），而25毫克曲马多的结果介于50毫克组和安慰剂组之间。50毫克静脉注射曲马多耐受性良好；最常见的TEAE是恶心和呕吐；在生命体征、心电图和实验室评估方面，各治疗组之间没有有意义的差异。与25毫克曲马多组（91.8%）和安慰剂组（88.2%）相比，完成50毫克曲马多治疗的患者比例最高（98.6%）。
50毫克静脉注射曲马多作为拇囊炎切除术后疼痛的治疗方法有效且耐受性良好，而25毫克静脉注射曲马多虽然耐受性良好，但在这种情况下被判定为无效剂量。50毫克静脉注射曲马多在美国注册项目中得到进一步研发。
ClinicalTrials.gov标识符，NCT03290378。
