No abstract

No abstract

No abstract

used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF <14 and ≥ 14). Analysis of covariance was used to analyse I-QOL scores. RESULTSThe mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of ≥ 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. CONCLUSIONSThese 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. KEYWORDSstress urinary incontinence, quality of life, duloxetine hydrochloride, serotonin, noradrenaline OBJECTIVESTo further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions,

Objective To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.Design Randomised double-blind, placebo-controlled clinical trial.Setting Fort-six centres in seven European countries and Canada.Population 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. Methods The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency !7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity !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. Intervention After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks. Main outcome measures 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. Results 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. Conclusions The findings support duloxetine as a potential treatment for women with stress urinary incontinence.