Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
J Pain Res. 2012;5:121-38. doi: 10.2147/JPR.S30540. Epub 2012 Jun 15.
This open-label, phase 3b study (ClinicalTrials.gov Identifier: NCT00983073) evaluated the effectiveness, and tolerability of tapentadol for severe, chronic osteoarthritis knee pain that was inadequately managed with World Health Organization (WHO) Step I or II analgesics or co-analgesics, or that was not treated with regular analgesics. Prior to starting study treatment, patients discontinued any WHO Step II analgesics, while Step I analgesics and/or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50-250 mg bid) during a 5-week titration period and a 7-week maintenance period. Doses of tapentadol immediate release 50 mg (≤twice/day; ≥4 hours apart) were permitted throughout the study (total daily dose of tapentadol prolonged and immediate release, ≤250 mg bid). The primary endpoint was the change in pain intensity on an 11-point numerical rating scale-3 (NRS-3; recalled average pain intensity [11-point NRS] during the last 3 days) from baseline to Week 6, using the last observation carried forward (LOCF) to impute missing pain intensity scores. The mean (standard deviation) change from baseline to Week 6 (LOCF) in pain intensity was -3.4 (2.10; P < 0.0001) for all patients evaluated for effectiveness (n = 195). Significant decreases in pain intensity were also observed at Weeks 6, 8, and 12 (all P < 0.0001) using observed-case analysis. Corresponding significant improvements from baseline to Weeks 6 and 12 were observed in the Western Ontario and McMaster Universities osteoarthritis index, the EuroQol-5 Dimension health status questionnaire, the Short Form-36 health survey, and the Hospital Anxiety and Depression Scale (all P ≤ 0.0103). Treatment-emergent adverse events were in line with those observed in previous studies of tapentadol prolonged release. Overall, the results of this study indicate that tapentadol treatment results in significant improvements in pain intensity, health-related quality of life, and function in patients with inadequately managed, severe, chronic osteoarthritis knee pain.
这项开放标签、3b 期研究（ClinicalTrials.gov 标识符：NCT00983073）评估了他喷他多治疗严重慢性膝关节骨关节炎疼痛的疗效和耐受性，这些患者对世界卫生组织（WHO）第一阶梯或第二阶梯镇痛药或辅助镇痛药治疗反应不足，或未接受常规镇痛药治疗。在开始研究治疗之前，患者停用所有 WHO 第二阶梯镇痛药，同时继续使用相同剂量的第一阶梯镇痛药和/或辅助镇痛药。患者在 5 周的滴定期和 7 周的维持期接受他喷他多缓释片（50-250mg，bid）治疗。整个研究期间允许使用他喷他多速释片 50mg（≤每日 2 次；≥4 小时 1 次）（他喷他多速释和缓释的总日剂量，bid 不超过 250mg）。主要终点是从基线到第 6 周时数字疼痛强度评分 3（NRS-3；最后 3 天回忆的平均疼痛强度[11 点 NRS]）的变化，采用最后观察结转（LOCF）来推断缺失的疼痛强度评分。所有有效性评估患者（n=195）的基线至第 6 周（LOCF）的疼痛强度平均（标准差）变化为-3.4（2.10；P＜0.0001）。使用观察病例分析，还观察到第 6、8 和 12 周时疼痛强度显著下降（均 P＜0.0001）。从基线到第 6 和 12 周时，Western Ontario 和 McMaster 大学骨关节炎指数、EuroQol-5 维度健康状况调查问卷、36 项简短健康调查问卷和医院焦虑抑郁量表也观察到相应的显著改善（均 P≤0.0103）。治疗中出现的不良事件与之前他喷他多缓释片研究观察到的一致。总的来说，这项研究的结果表明，他喷他多治疗可显著改善治疗反应不足的严重慢性膝关节骨关节炎疼痛患者的疼痛强度、健康相关生活质量和功能。
