Once daily trospium chloride is effective and well tolerated for the treatment of overactive bladder: results from a multicenter phase III trial.

Department of Urology, New York Presbyterian Hospital, Weill-Cornell Medical College, New York, New York 10021, USA.
The Journal of Urology (Impact Factor: 3.7). 10/2007; 178(3 Pt 1):978-83; discussion 983-4. DOI: 10.1016/j.juro.2007.05.058
Source: PubMed

ABSTRACT An extended release formulation of trospium chloride was recently developed for the once daily treatment of overactive bladder. We investigated the safety, efficacy and tolerability of 60 mg trospium chloride once daily.
Subjects with overactive bladder were randomized 1:1 to receive 60 mg trospium chloride once daily or placebo in this 12-week multicenter, parallel, double-blind, placebo controlled trial. Primary end points were calculated changes in diary recorded daily urinary frequency and daily urgency urinary incontinence episodes. Secondary end points were urgency severity, volume voided per void and the number of urgency voids per day. Safety was assessed by clinical examination, adverse event monitoring, clinical laboratory values and resting electrocardiograms.
Overall 601 subjects were prescribed trospium once daily (298) or placebo (303). Trospium once daily treatment resulted in significant improvements over placebo in all primary and key secondary efficacy outcomes at weeks 1 through 12. The most common adverse events were dry mouth (trospium 8.7% vs placebo 3%) and constipation (trospium 9.4% vs placebo 1.3%). Central nervous system adverse events were rare (headache with trospium 1.0% vs placebo 2.6%). No clinically meaningful changes in laboratory, physical examination or electrocardiogram parameters were noted.
Trospium once daily provided significant improvements in overactive bladder symptoms (frequency, urgency urinary incontinence and urgency). Efficacy was similar to that seen previously with trospium chloride twice daily, while class effect anticholinergic adverse events occurred at comparatively low levels. Dry mouth was elicited at the lowest reported rate in the oral antimuscarinic drug class.

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    ABSTRACT: Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3-adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms. To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50mg versus antimuscarinics in patients with OAB. A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision). Overall, 44 RCTs involving 27 309 patients were included. The MTCs showed that mirabegron 50mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10mg that was more efficacious than mirabegron 50mg in improving micturition frequency and frequency of UUI. Mirabegron 50mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics. Mirabegron 50mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.
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