van Kerrebroeck Philip, Abrams Paul, Lange Rainer, Slack Mark, Wyndaele Jean-Jacques, Yalcin Ilker, Bump Richard C
Department of Urology, University Hospital Maastrecht, Netherlands.
BJOG. 2004 Mar;111(3):249-57. doi: 10.1111/j.1471-0528.2004.00067.x.
To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.
Randomised double-blind, placebo-controlled clinical trial.
Fort-six centres in seven European countries and Canada.
Four hundred and ninety-four women aged 24-83 years identified as having predominant symptoms of stress urinary incontinence using a clinical algorithm that was 100% predictive of urodynamic stress urinary incontinence in a subgroup of 34 women.
The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency > or =7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity > or =400 mL and both a positive cough stress test and positive stress pad test. Subjects completed two urinary diaries prior to randomisation and three diaries during the active treatment phase of the study, each completed during the week prior to monthly visits. Subjects also completed quality of life questionnaires at each visit. Safety was assessed by the evaluation of treatment-emergent adverse events, discontinuation of treatment because of adverse events, serious adverse events, vital sign measurements, electrocardiograms (ECG) and clinical laboratory tests.
After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks.
The percentage decrease in incontinence episode frequency and the change in the Incontinence Quality of Life (I-QOL) questionnaire total score were prespecified as co-primary outcome variables in the protocol.
Incontinence episode frequency decreased significantly with duloxetine compared with placebo (median decrease of 50%vs 29%; P= 0.002) with comparable improvements in the more severely incontinent subgroup (those experiencing at least 14 incontinence episodes per week at baseline; 56%vs 27% decreases; P < 0.001). The primary analysis of I-QOL scores did not reveal a significant difference between treatment groups, due primarily to the carrying forward of low scores from patients who discontinued treatment very early due to duloxetine-associated adverse events. The increase in I-QOL scores was significantly greater for duloxetine than for placebo at each of the three postrandomisation visits after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events were higher for duloxetine (22%vs 5%; P < 0.001) with nausea being the most common reason for discontinuation (5.3%). Nausea tended to be mild to moderate, not progressive, and transient.
The findings support duloxetine as a potential treatment for women with stress urinary incontinence.
评估度洛西汀治疗女性压力性尿失禁的疗效和安全性。
随机双盲、安慰剂对照临床试验。
欧洲七个国家和加拿大的46个中心。
494名年龄在24 - 83岁的女性，通过一种临床算法确定为主要表现为压力性尿失禁症状，该算法在34名女性亚组中对尿动力学压力性尿失禁的预测准确率为100%。
病例定义包括主要表现为压力性尿失禁，每周尿失禁发作频率≥7次，无主要的急迫性尿失禁症状，昼夜排尿频率正常，膀胱容量≥400 mL，且咳嗽压力试验和压力垫试验均为阳性。受试者在随机分组前完成两份排尿日记，在研究的积极治疗阶段完成三份日记，每份日记在每月就诊前一周完成。受试者在每次就诊时还需完成生活质量问卷。通过评估治疗中出现的不良事件、因不良事件停药情况、严重不良事件、生命体征测量、心电图（ECG）和临床实验室检查来评估安全性。
经过两周的安慰剂导入期后，女性接受安慰剂或度洛西汀40 mg每日两次，持续12周。
失禁发作频率的下降百分比和尿失禁生活质量（I - QOL）问卷总分的变化在方案中预先指定为共同主要观察变量。
与安慰剂相比，度洛西汀治疗后失禁发作频率显著降低（中位数下降50%对29%；P = 0.002），在失禁更严重的亚组（基线时每周至少经历14次失禁发作的患者；下降56%对27%；P < 0.001）中改善程度相当。I - QOL评分的初步分析未显示治疗组之间存在显著差异，主要原因是因度洛西汀相关不良事件而很早就停药的患者的低分被结转。在治疗4、8和12周后的三次随机分组后就诊中，度洛西汀组的I - QOL评分增加均显著高于安慰剂组。度洛西汀组因不良事件停药率更高（22%对5%；P < 0.001），恶心是最常见的停药原因（5.3%）。恶心倾向于轻度至中度，无进展且为短暂性。
研究结果支持度洛西汀作为女性压力性尿失禁的一种潜在治疗方法。
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