Serrie Alain, Lange Bernd, Steup Achim
a Service de Médecine de la Douleur et de Médecine Palliative, Universités Paris Descartes - Paris Diderot Hôpital Lariboisière , Paris , France.
b Grünenthal GmbH , Aachen , Germany.
Curr Med Res Opin. 2017 Aug;33(8):1423-1432. doi: 10.1080/03007995.2017.1335189. Epub 2017 Jun 11.
To assess efficacy and safety of tapentadol prolonged release (PR) for moderate-to-severe chronic osteoarthritis knee pain.
Patients (n = 990) were randomized (1:1:1) to tapentadol PR, oxycodone controlled release (CR; reference compound for assay sensitivity), or placebo for a double-blind 3-week titration and 12-week maintenance period. Primary efficacy end-points were change from baseline in average pain intensity at week 12 of maintenance (US end-point) and over the entire maintenance period (non-US end-point) with "last observation carried forward" as imputation method for missing scores.
Both primary end-points were not significantly different for tapentadol PR nor for oxycodone CR vs placebo at week 12 (least squares [LS] mean difference = -0.3 [95% CI = -0.61-0.09]; p = 0.152 and 0.2 [95% CI = -0.16-0.54]; p = 0.279, respectively) and over the maintenance period (LS mean difference = -0.2 [95% CI = -0.55-0.07]; p = 0.135 and 0.1 [95% CI = -0.18-0.44]; p = 0.421, respectively). Considerably more patients receiving tapentadol PR than oxycodone CR completed the trial (58.3% vs 36.6%). This is consistent with better results with tapentadol PR on the overall health status (PGIC) compared to oxycodone CR. Indeed, respectively, 56% and 42.5% rated at least "much improved" at the end of treatment. Incidences of gastrointestinal adverse events were higher for both active treatments compared to placebo. Tapentadol PR was associated with a better gastrointestinal tolerability profile with incidences of constipation (17.9% vs 35%) and of the composite of nausea and/or vomiting (23.8% vs 46.8%) significantly lower vs oxycodone CR (p < 0.001).
The study did not demonstrate assay sensitivity. The finding that both primary end-points for tapentadol PR were not met can, thus, not be interpreted. Tapentadol PR was better tolerated than oxycodone CR, largely due to fewer gastrointestinal side-effects.
评估缓释他喷他多治疗中重度慢性膝骨关节炎疼痛的疗效和安全性。
990例患者按1:1:1随机分组，分别接受缓释他喷他多、羟考酮控释片（用于测定灵敏度的参比化合物）或安慰剂治疗，进行为期3周的双盲滴定和12周的维持治疗。主要疗效终点为维持期第12周（美国终点）和整个维持期（非美国终点）平均疼痛强度较基线的变化，采用“末次观察结转”法对缺失评分进行插补。
在第12周时，缓释他喷他多和羟考酮控释片与安慰剂相比，两个主要终点均无显著差异（最小二乘均值差异=-0.3 [95%置信区间=-0.61-0.09]；p=0.152和0.2 [95%置信区间=-0.16-0.54]；p=0.279），在维持期内也无显著差异（最小二乘均值差异=-0.2 [95%置信区间=-0.55-0.07]；p=0.135和0.1 [95%置信区间=-0.18-0.44]；p=0.421）。接受缓释他喷他多治疗完成试验的患者比接受羟考酮控释片治疗的患者多得多（58.3%对36.6%）。这与缓释他喷他多在总体健康状况（PGIC）方面比羟考酮控释片效果更好一致。实际上，分别有56%和42.5%的患者在治疗结束时至少评定为“大有改善”。与安慰剂相比，两种活性治疗的胃肠道不良事件发生率均较高。缓释他喷他多的胃肠道耐受性较好，便秘发生率（17.9%对35%）以及恶心和/或呕吐的综合发生率（23.8%对46.8%）均显著低于羟考酮控释片（p<0.001）。
该研究未证明测定灵敏度。因此，无法解读缓释他喷他多未达到两个主要终点这一结果。缓释他喷他多的耐受性优于羟考酮控释片，主要是因为胃肠道副作用较少。
