Institute for Neurological Sciences, Algesiology and Pediatrics, Nuernberg, Germany.
Curr Med Res Opin. 2012 Oct;28(10):1617-34. doi: 10.1185/03007995.2012.726216. Epub 2012 Sep 12.
To demonstrate non-inferior/superior efficacy of flupirtine modified release (MR) compared with tramadol/placebo for the management of moderate to severe chronic low back pain (LBP).
Randomized, double-blind, active-/placebo-controlled double-dummy multicenter study, performed in 31 German study centers. LBP patients (n = 363) with moderate pain intensity were randomized 1:1:1 to receive flupirtine MR 400 mg, tramadol extended release (ER) 200 mg, or matching placebo (each given OD in the evening) over 4 weeks.
EudraCT 2009-013268-38.
Primary endpoint was change from baseline in the LBP intensity index (LBPIX; 11-point NRS) at week 4; last observation carried forward was used to impute missing scores.
Least square (LS) mean ± SD LBPIX changes from baseline at week 4 were clinically significant for all three treatment groups of the intent-to-treat (ITT) and the per-protocol (PP) population (n = 326/276): placebo (n = 110/96): -1.81 ± 1.65/-1.77 ± 1.59; flupirtine MR (n = 109/95): -2.23 ± 1.73/-2.28 ± 1.68; and tramadol ER (n = 107/85): -1.92 ± 1.84/2.03 ± 1.83 (p < 0.001 for each). ITT/PP treatment effects for flupirtine MR were non-inferior when compared with tramadol ER and superior when compared with placebo (p = 0.003/0.033). Significantly more ITT patients treated with flupirtine MR (59.6/37.6 showed a ≥30/50% LBPIX relief in comparison to placebo (46.4/24.6%; p vs. flupirtine MR: 0.049/0.037). Treatment contrasts for tramadol failed to reach significance vs. placebo. Within the safety population (n = 355), flupirtine MR (n = 119) was associated with a significantly lower incidence of treatment emergent AEs (TEAEs; 21.0%) and TEAE-related study discontinuations (3.4%) than tramadol ER (n = 116; 34.5/12.0%; p = 0.039/0.017) and exhibited an overall safety/tolerability profile non-inferior to placebo (n = 120; 15.8/3.3%; p = ns for each). Major limitations of this study were the short treatment duration, the comparison of different drug classes and the lack of a titration phase.
The analgesic efficacy of flupirtine MR 400 mg OD was comparable to that of tramadol ER 200 mg OD and superior to that of placebo.
证明氟吡汀控释制剂（MR）与曲马多/安慰剂相比，在治疗中度至重度慢性下背痛（LBP）方面具有非劣效/优效疗效。
这是一项在 31 个德国研究中心进行的随机、双盲、活性药物/安慰剂对照、双盲、多中心研究。将中度疼痛强度的 LBP 患者（n=363）随机分为 1:1:1 组，分别接受氟吡汀 MR 400mg、曲马多缓释片（ER）200mg 或匹配安慰剂（均每晚 1 次），治疗 4 周。
EudraCT 2009-013268-38。
主要终点为第 4 周时 LBP 强度指数（LBPIX；11 点 NRS）与基线相比的变化；最后观察值为缺失值插补。
在意向治疗（ITT）和方案人群（n=326/276）中，所有三组治疗（氟吡汀 MR、曲马多 ER 和安慰剂）的 LS 均值±SD LBPIX 变化在第 4 周均具有临床意义：安慰剂（n=110/96）：-1.81±1.65/-1.77±1.59；氟吡汀 MR（n=109/95）：-2.23±1.73/-2.28±1.68；曲马多 ER（n=107/85）：-1.92±1.84/2.03±1.83（p<0.001）。与曲马多 ER 相比，氟吡汀 MR 的 ITT/PP 治疗效果非劣效，与安慰剂相比则具有优势（p=0.003/0.033）。与安慰剂相比，接受氟吡汀 MR 治疗的 ITT 患者（59.6%/37.6%）有更多患者出现≥30%/50%的 LBPIX 缓解，而安慰剂组分别为 46.4%/24.6%（p 与氟吡汀 MR 相比：0.049/0.037）。曲马多治疗的治疗对比未达到与安慰剂的统计学意义。在安全性人群（n=355）中，氟吡汀 MR（n=119）与曲马多 ER（n=116）相比，治疗出现的不良事件（TEAE）发生率（21.0%）和因 TEAE 而导致的研究中止率（3.4%）显著降低（p=0.039/0.017），并且整体安全性/耐受性与安慰剂（n=120）相当（15.8%/3.3%；p 对于每个）。本研究的主要局限性是治疗持续时间短、不同药物类别比较和缺乏滴定阶段。
氟吡汀 MR 400mg 每日 1 次的镇痛疗效与曲马多 ER 200mg 每日 1 次相当，优于安慰剂。
