Millard R J, Moore K, Rencken R, Yalcin I, Bump R C
The Prince of Wales Hospital, Sydney, Australia.
BJU Int. 2004 Feb;93(3):311-8. doi: 10.1111/j.1464-410x.2004.04607.x.
To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women.
The study included 458 women aged 27-79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF < 14 and > or = 14). Analysis of covariance was used to analyse I-QOL scores.
The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of > or = 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial.
These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.
在一项3期研究中，对度洛西汀治疗阿根廷、澳大利亚、巴西、芬兰、波兰、南非和西班牙等其他地理区域压力性尿失禁（SUI）女性的情况进行进一步评估，因为此前在北美和欧洲进行的试验已提供证据表明度洛西汀作为女性SUI的药物治疗具有安全性和有效性。
该研究纳入了458名年龄在27 - 79岁的女性，她们参与了一项双盲、安慰剂对照试验。主要为SUI的患者通过经过验证的临床算法进行识别。她们被随机分配接受安慰剂（231例）或度洛西汀40毫克每日两次（227例），为期12周。主要结局变量包括尿失禁发作频率（IEF）和尿失禁生活质量（I - QOL）问卷。使用范埃尔特伦检验分析IEF的百分比变化，分层变量为每周基线IEF（IEF < 14和≥14）。采用协方差分析来分析I - QOL评分。
平均基线IEF为每周18.4次；55%的患者基线IEF≥14。度洛西汀组的IEF中位数下降幅度显著大于安慰剂组（54%对40%，P = 0.05），生活质量也有相当显著的改善（I - QOL评分增加10.3对6.4，P = 0.007）。度洛西汀带来的改善与排尿间隔时间的显著增加相关，且大于安慰剂组（20.4对8.5分钟，P < 0.001）。安慰剂反应比两项欧洲和北美3期试验报告的高10.7%和12.5%。这可能与当前试验中更多患者对尿失禁管理缺乏经验有关。安慰剂组不良事件停药率为1.7%，度洛西汀组为17.2%（P < 0.001），恶心是最常见的停药原因（3.1%）；恶心是度洛西汀最常见的不良事件，但大多数（81%）为轻度或中度，没有患者症状加重，60%的持续用药患者在7天内症状缓解，86%在1个月内缓解；88%服用度洛西汀时出现恶心的女性完成了试验。
这些结果表明，每日两次服用40毫克度洛西汀，持续12周，可改善尿失禁和生活质量，这与欧洲和北美最近完成的另外两项3期试验报告的结果一致。
