Department of Nephrology, National Defense Medical College, Japan.
Nephrol Dial Transplant. 2010 Apr;25(4):1251-7. doi: 10.1093/ndt/gfp588. Epub 2009 Nov 19.
Pruritus in haemodialysis patients is an intractable disease and substantially impairs their quality of life. Based on the results of our earlier clinical study, we hypothesized that the micro-(mu) opioid system is itch-inducible, whereas the kappa (kappa) system is itch-suppressive.
The efficacy and safety of nalfurafine hydrochloride (a novel kappa-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 microg of the drug or a placebo orally for 14 days using a double-blind design in 337 haemodialysis patients with itch that was resistant to currently available treatments, such as antihistamines.
The mean decrease in the visual analogue scale (VAS) from baseline, the study's primary endpoint, was significantly larger in the 5-microg nalfurafine hydrochloride group (n = 114) than in the placebo group (n = 111, P = 0.0002, one-sided test at 2.5% significance level). The decrease in the VAS in the 2.5-microg group (n = 112) was also significantly larger than that in the placebo group (P = 0.0001). The incidence of adverse drug reactions (ADRs) was 35.1% in the 5-microg group, 25.0% in the 2.5-microg group and 16.2% in the placebo group. Moderate to severe ADRs were observed in 10 of the 226 patients. The most common ADR was insomnia (sleep disturbance), seen in 24 of the 226 nalfurafine patients.
This Phase III, randomized, double-blind, placebo-controlled, parallel-group, prospective study based on VAS evaluations clearly showed that orally taken nalfurafine hydrochloride effectively reduced itches that were otherwise refractory to currently available treatments in maintenance haemodialysis patients, with few significant ADRs. This novel drug was officially approved for clinical use in January 2009 by the Ministry of Health, Labour and Welfare of Japan.
在血液透析患者中，瘙痒是一种难以治愈的疾病，严重影响了他们的生活质量。基于我们早期临床研究的结果，我们假设微（mu）阿片系统是瘙痒诱导的，而kappa（kappa）系统是瘙痒抑制的。
采用随机（1:1:1）、双盲设计，对 337 例对现有治疗（如抗组胺药）无效的瘙痒的血液透析患者，分别给予 5 或 2.5 microg 盐酸纳呋拉啡（一种新型的 kappa 受体激动剂）或安慰剂，连续口服 14 天，前瞻性评估其疗效和安全性。
主要终点为视觉模拟量表（VAS）自基线的平均下降，5-microg 盐酸纳呋拉啡组（n = 114）显著大于安慰剂组（n = 111，P = 0.0002，单侧检验，2.5%显著性水平）。2.5-microg 组（n = 112）的 VAS 下降也显著大于安慰剂组（P = 0.0001）。5-microg 组不良反应（ADR）发生率为 35.1%，2.5-microg 组为 25.0%，安慰剂组为 16.2%。226 例患者中有 10 例发生中度至重度 ADR。最常见的不良反应是失眠（睡眠障碍），226 例纳呋拉啡患者中有 24 例出现。
本项基于 VAS 评估的 III 期、随机、双盲、安慰剂对照、平行组、前瞻性研究清楚地表明，口服盐酸纳呋拉啡可有效减轻维持性血液透析患者对现有治疗无效的瘙痒，不良反应发生率低。这种新药于 2009 年 1 月获得日本厚生劳动省的批准用于临床。
