BACKGROUND:Overactive bladder syndrome (OAB) is associated with various co-morbidities; treatment of these frequently results in multiple medication use (MMU) and the potential for drug-drug interactions, which may lead to adverse events and altered efficacy. With the aging population, the prevalence of MMU is likely to increase in the overall population, an increase due in part to treatment of co-morbidities that are more common in the elderly. OBJECTIVE: To assess safety and efficacy outcomes with once-daily trospium chloride 60 mg extended release (XR) in subjects with OAB who were taking multiple concomitant medications. STUDY DESIGN: Post hoc analysis of pooled data from two 12-week randomized, placebo-controlled studies. SETTING: Urology, urogynaecology, and primary care offices/clinics. PATIENTS: Subjects aged ≥18 years with OAB for ≥6 months who had baseline urinary frequency of ≥30 toilet voids/3 days; ≥1 'severe' urgency severity rating/3 days (on the Indevus Urgency Severity Scale); and pure urge urinary incontinence (UUI) or mixed incontinence with predominant UUI, with ≥3 UUI episodes/3 days. This analysis utilized data from subjects taking concomitant medications, focusing on those taking seven or more. INTERVENTION: Once-daily trospium chloride 60 mg XR or placebo. MAIN OUTCOME MEASURE: Predictors of treatment-emergent adverse events (TEAEs) identified by multivariate logistic regression analysis. RESULTS: Concomitant medications were being taken by 1135 subjects (placebo, n = 576; trospium chloride XR, n = 559); 427 were taking seven or more (placebo, n = 199; trospium XR, n = 228). Among subjects taking seven or more concomitant medications, there was no significant difference between trospium chloride XR and placebo in the proportion of subjects experiencing one or more TEAEs (64.5% vs 58.3%). Logistic regression analysis indicated that the odds of experiencing a TEAE were influenced by concomitant medication use, but not by randomization assignment to trospium chloride XR or to placebo, suggesting that concomitant drugs contribute more to TEAEs than trospium chloride XR. Compared with subjects taking one to two concomitant medications, the adjusted odds ratio (OR) for experiencing any TEAE was 3.39 (95% CI 2.39, 4.80; p < 0.0001) for subjects taking seven or more concomitant medications. The adjusted OR for experiencing any TEAE for subjects randomized to active treatment compared with placebo was 1.19 (95% CI 0.85, 1.67; p = 0.31). Efficacy in subjects taking seven or more concomitant medications was similar to that in the overall pooled study population. CONCLUSIONS:Trospium chloride XR does not increase the likelihood of a TEAE compared with placebo. The probability of experiencing a TEAE was significantly influenced by use of multiple concomitant medications. Trospium chloride XR was as effective in subjects with OAB taking seven or more concomitant medications as in the overall pooled study population. The data support the conclusion that trospium chloride XR is safe and effective in patients with OAB taking multiple concomitant medications.
RCT Entities:
BACKGROUND:Overactive bladder syndrome (OAB) is associated with various co-morbidities; treatment of these frequently results in multiple medication use (MMU) and the potential for drug-drug interactions, which may lead to adverse events and altered efficacy. With the aging population, the prevalence of MMU is likely to increase in the overall population, an increase due in part to treatment of co-morbidities that are more common in the elderly. OBJECTIVE: To assess safety and efficacy outcomes with once-daily trospium chloride 60 mg extended release (XR) in subjects with OAB who were taking multiple concomitant medications. STUDY DESIGN: Post hoc analysis of pooled data from two 12-week randomized, placebo-controlled studies. SETTING: Urology, urogynaecology, and primary care offices/clinics. PATIENTS: Subjects aged ≥18 years with OAB for ≥6 months who had baseline urinary frequency of ≥30 toilet voids/3 days; ≥1 'severe' urgency severity rating/3 days (on the Indevus Urgency Severity Scale); and pure urge urinary incontinence (UUI) or mixed incontinence with predominant UUI, with ≥3 UUI episodes/3 days. This analysis utilized data from subjects taking concomitant medications, focusing on those taking seven or more. INTERVENTION: Once-daily trospium chloride 60 mg XR or placebo. MAIN OUTCOME MEASURE: Predictors of treatment-emergent adverse events (TEAEs) identified by multivariate logistic regression analysis. RESULTS: Concomitant medications were being taken by 1135 subjects (placebo, n = 576; trospium chloride XR, n = 559); 427 were taking seven or more (placebo, n = 199; trospium XR, n = 228). Among subjects taking seven or more concomitant medications, there was no significant difference between trospium chloride XR and placebo in the proportion of subjects experiencing one or more TEAEs (64.5% vs 58.3%). Logistic regression analysis indicated that the odds of experiencing a TEAE were influenced by concomitant medication use, but not by randomization assignment to trospium chloride XR or to placebo, suggesting that concomitant drugs contribute more to TEAEs than trospium chloride XR. Compared with subjects taking one to two concomitant medications, the adjusted odds ratio (OR) for experiencing any TEAE was 3.39 (95% CI 2.39, 4.80; p < 0.0001) for subjects taking seven or more concomitant medications. The adjusted OR for experiencing any TEAE for subjects randomized to active treatment compared with placebo was 1.19 (95% CI 0.85, 1.67; p = 0.31). Efficacy in subjects taking seven or more concomitant medications was similar to that in the overall pooled study population. CONCLUSIONS:Trospium chloride XR does not increase the likelihood of a TEAE compared with placebo. The probability of experiencing a TEAE was significantly influenced by use of multiple concomitant medications. Trospium chloride XR was as effective in subjects with OAB taking seven or more concomitant medications as in the overall pooled study population. The data support the conclusion that trospium chloride XR is safe and effective in patients with OAB taking multiple concomitant medications.
Authors: Paul Abrams; Linda Cardozo; Magnus Fall; Derek Griffiths; Peter Rosier; Ulf Ulmsten; Philip Van Kerrebroeck; Arne Victor; Alan Wein Journal: Urology Date: 2003-01 Impact factor: 2.649
Authors: Pieter J Swart; Walter J J Krauwinkel; Ronald A Smulders; Neila N Smith Journal: Basic Clin Pharmacol Toxicol Date: 2006-07 Impact factor: 4.080