Mean Number Of Incontinence Episodes Research Articles

Effect of Electroacupuncture Added to Pelvic Floor Muscle Training in Women with Stress Urinary Incontinence: A Randomized Clinical Trial

BackgroundPelvic floor muscle training (PFMT) is a first-line conservative therapy for stress urinary incontinence (SUI). Electroacupuncture (EA) has been used to treat SUI recently. ObjectiveTo compare the effectiveness of PFMT + EA versus PFMT + sham EA for SUI in women. Design, setting, and participantsA prospective, multicenter, randomized, controlled clinical trial was conducted at four hospitals in China involving 304 women with SUI from May 20, 2014 to November 21, 2017. Data were analyzed from April 20 to December 21, 2018. InterventionParticipants were randomized to receive 8 wk of PFMT+ EA (n = 154) or PFMT + sham EA (n = 150). Outcome measurements and statistical analysisThe primary outcome was the change in the amount of urine leakage measured on a 1-hr pad test. Student’s t test, the χ2 test, and the Wilcoxon rank-sum test were used for data analysis. Results and limitationsAmong the 304 participants randomized, 286 completed the study. The mean age was 57.6 yr (standard deviation [SD] 8.9) for the PFMT + sham EA group and 57.2 yr (SD 9.1) for the PFMT + EA group. The mean urine leakage at baseline was 13.6 g for the PFMT + sham EA group and 13.9 g for the PFMT + EA group. After the 8-wk intervention, the PFMT + EA group had a greater decrease in mean urine leakage (−9.8 g) than the PFMT + sham EA group (−5.8 g) with a mean difference of 4.0 g (95% confidence interval [CI] 0.8–7.2). Significantly more patients experienced a ≥50% reduction in urine leakage and the mean number of incontinence episodes in 24 h in the PFMT + EA group than in the PFMT + sham EA group (26.3%, 95%CI 15.8–36.8%). The PFMT + EA group experienced better improvement in participant-reported SUI severity at 6 wk (p < 0.001) and 8 wk (p < 0.001) and self-evaluated therapeutic effects at 2–32 wk (p < 0.001) after the intervention. Lack of measurement of the amount of urine leakage during follow-up is a limitation. ConclusionsIn this randomized clinical trial, 8-wk combined treatment with PFMT + EA led to a greater improvement in SUI symptoms and better outcomes than with PFMT + sham EA. Patient summaryWe evaluated the effectiveness and safety of pelvic floor muscle training combined with electroacupuncture for stress urinary incontinence in women, Our results show that this is a promising therapeutic approach for the treatment of stress urinary incontinence.

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study.

To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI). This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline. A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 mlto 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 hto 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H2 O to 41 cm H2 O(p = .005) at 6 weeks. Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment. Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

Injectable bulking treatment of persistent fecal incontinence in adult patients after anorectal malformations

Background/PurposeInjectable bulking therapy has emerged as a treatment for fecal incontinence (FI), however there are no studies including adult patients with anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI. MethodsSeven adults with ARM and incontinence to loose stool at least once weekly and without rectal or mucosal prolapse were treated with anal NASHA/Dx injection. They were evaluated preoperatively, at 6 and 18 months with a bowel function questionnaire and a 2-week bowel diary as well as FIQL and SF-36 quality of life questionnaires. ResultsBefore treatment, the mean number of incontinence episodes over 2 weeks was 20.7 (median 16, range 8–52). At 6 months, the corresponding figures were 5.3 (median 4, range 0–19, p = 0.018), and at 18 months the figures were 4.3 (median 2, range 1–20, p = 0.018). An improved physical function in SF-36 from 74.3 at baseline to 86.4 at 6 months was noted (p = 0.04). No serious adverse events occurred. ConclusionsNASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Longer follow up of larger patient series and studies on patients in adolescence is needed. Type of StudyTreatment Study. Level of EvidenceLevel IV.

Meta-analysis of the efficacy and safety of mirabegron and solifenacin monotherapy for overactive bladder.

We conducted a meta-analysis to evaluate the safety and efficacy of mirabegron (50 mg) and solifenacin (5 mg) monotherapy for overactive bladder (OAB) during a 12-week cycle. Randomized controlled trials (RCTs) of mirabegron and solifenacin for OAB were searched systematically by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of retrieved studies were also perused. Five RCTs which compared solifenacin with mirabegron were studied. Mirabegron achieved the same effect as solifenacin in treating OAB. The mean number of incontinence episodes per 24 h (P = 0.20), mean number of micturitions per 24 h (P = 0.11), mean number of urgency episodes per 24 h (P = 0.23), and mean volume voided per micturition (P = 0.05) suggested that mirabegron and solifenacin had no significant differences in terms of OAB treatment. With regard to drug-related treatment-emergent adverse events (DR-TEAEs) and dry mouth, mirabegron showed better tolerance than solifenacin. Post-voiding residual volume showed a distinct difference in the two groups. Hypertension and tachycardia did not show a significant difference between the two groups, but the pulse rate did. The therapeutic effect of mirabegron is similar to that of solifenacin, and mirabegron does not increase the risk of adverse events (AEs).

Factors influencing efficacy endpoints in clinical trials for new oral medicinal treatments for overactive bladder: a systematic literature review and meta-analysis.

Overactive bladder (OAB) is a symptom-based disease; therefore, clinical trials to evaluate treatments for OAB employ a range of efficacy endpoints. Since factors that influence efficacy endpoints can affect trial outcomes, their identification could aid in the design of future OAB clinical trials. We investigated factors influencing different efficacy endpoints used in clinical trials with OAB patients and examined their characteristics to determine future clinical trial strategies for new medicinal treatments for OAB. Data from placebo-controlled double-blind trials in patients with OAB were extracted via a systematic literature review. The integrated differences for efficacy endpoints were calculated. Heterogeneity was assessed using the Q statistic and I2 statistic. Factors influencing efficacy endpoints were identified through univariate and multivariate meta-regression analyses. Forty-one controlled trials were analyzed. Substantial heterogeneity between studies was observed for each efficacy endpoint (P > 0.001, I2 > 70%). We found with multivariate meta-regression analysis that period of recording in a bladder diary and year of publication were significantly likely to influence the change from baseline in the mean number of urgency episodes in 24h, year of publication and gender were significantly likely to influence the change from baseline in the mean number of micturitions in 24h, and gender was significantly likely to influence the change from baseline in the mean volume voided per micturition. In contrast, there were no factors significantly associated with change from baseline in the mean number of incontinence episodes in 24h. We identified that change from baseline in the mean number of incontinence episodes in 24h should serve as a relatively stable endpoint. In contrast, we identified factors influencing other endpoints, and the identified factors should be taken into account when planning and conducting future clinical trials.

Potential Primary Endpoint for Exploratory Clinical Trial in Patients with Overactive Bladder: A Systematic Literature Review.

To identify a potential primary endpoint in an early-phase exploratory trial among key overactive bladder (OAB) symptoms. Placebo-controlled double-blinding trials in patients with OAB were extracted for systematic literature review. The correlation between key OAB symptoms recorded in bladder diaries and coefficient of variation (CV) in each study were assessed. Forty-one controlled trials were extracted for the present review. Mean number of urgency episodes in 24 h was substantially associated with mean number of urgency incontinence episodes in 24 h, mean volume voided per micturition, and mean number of micturitions in 24 h (Spearman's r = 0.725, -0.661, and 0.657, respectively). Mean number of micturitions in 24 h was also substantially associated with mean volume voided per micturition (Spearman's r = -0.674). Mean number of incontinence episodes in 24 h was substantially associated with mean number of urgency incontinence episodes in 24 h and mean volume voided per micturition (Spearman's r = 0.840 and -0.628, respectively). The median CV of mean volume voided per micturition in each trial was the smallest among all endpoints. Our findings suggest that volume voided per micturition is a useful symptom for evaluating OAB candidate compounds in a small sample size and represents an effective primary endpoint, especially in exploratory clinical trials.

Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE)

BackgroundIncontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. ObjectiveTo evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg. Design, setting, and participantsOAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4. Outcome measurements and statistical analysisThe primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy. Results and limitationsA total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated. ConclusionsAdding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg. Patient summaryIn this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. Trial registrationClinicalTrials.gov NCT01908829.

Mirabegron: a Beta-3 agonist for overactive bladder.

To review the literature regarding the efficacy and safety of mirabegron for the treatment of overactive bladder (OAB). A literature search was performed using MEDLINE (PubMed) prior to December 31, 2013, using the terms "mirabegron" and "randomized-controlled trial." All published, double-blind, randomized-controlled trials assessing mirabegron were included. Articles were reviewed and included if mirabegron was used as monotherapy and if the primary outcome analyzed drug efficacy. The efficacy of mirabegron for the treatment of OAB has been demonstrated in the selected five randomized, placebo-controlled trials. The majority of these trials lasted 12 weeks and compared various doses of mirabegron with placebo and/or tolterodine extended-release (ER). Primary efficacy outcomes for the trials included mean number of micturitions per 24 hours and mean number of incontinence episodes per 24 hours. Included trials showed statistically significant reductions in both efficacy outcomes for various doses of mirabegron when compared with placebo. Based on the trials reviewed, mirabegron has been efficacious in reducing mean number of micturitions and incontinence episodes per 24 hours, as well as in improving other secondary outcomes such as OAB symptoms and quality-of-life measures. Common adverse drug events seen with mirabegron include: hypertension, nasopharyngitis, urinary tract infections, headache, constipation, upper respiratory tract infection, arthralgia, diarrhea, tachycardia, abdominal pain, and fatigue. Given the efficacy and safety data currently available, mirabegron represents a reasonable alternative to antimuscarinics for patients with OAB. Future studies are needed to determine the utility of mirabegron for OAB in a variety of demographics.

The Role of Mirabegron in Overactive Bladder: A Systematic Review and Meta-Analysis

Objective: To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB). Materials and Methods: A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis. Results: We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04). Conclusions: In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.

Efficacy of the β3-adrenoceptor Agonist Mirabegron for the Treatment of Overactive Bladder by Severity of Incontinence at Baseline: A Post Hoc Analysis of Pooled Data from Three Randomised Phase 3 Trials

The β3-adrenoceptor agonist mirabegron is approved for treatment of the symptoms of overactive bladder (OAB). Incontinence can be the most bothersome of OAB symptoms. Hence, we conducted a post hoc analysis of pooled data from three randomised, double-blind, placebo-controlled, 12-wk, phase 3 studies of mirabegron to evaluate the efficacy of mirabegron 50mg in incontinent OAB patients and in subgroups of patients stratified by severity of incontinence at baseline (an average of two or more [FAS-I≥2 subgroup] or four or more [FAS-I≥4 subgroup] incontinence episodes per 24h at baseline, where FAS-I is the full analysis set-incontinence population) and to determine correlations between measures of efficacy and disease severity. Mirabegron 50mg resulted in statistically significant improvements from baseline to final visit versus placebo in mean number of incontinence episodes, micturitions, and urgency episodes per 24h and mean volume voided per micturition in the pooled incontinent population and in the FAS-I≥2 and FAS-I≥4 subgroups. Treatment effect versus placebo for incontinence and urgency episodes increased with increasing severity of incontinence at baseline. Moderate correlations were seen between improvement in both frequency of incontinence episodes and micturitions and baseline incontinence and micturition frequency, respectively, with mirabegron 50mg and placebo. Patient summaryIncontinence can be the most bothersome of OAB symptoms; mirabegron 50mg once daily is effective for treatment of OAB symptoms in incontinent patients, and its effect increases with increasing severity of incontinence.

The efficacy and safety of mirabegron in treating OAB: a systematic review and meta-analysis of phase III trials

Mirabegron, a potent and selective β3-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating OAB. A literature review was performed to identify all published randomized double-blind, placebo-controlled phase III trials of mirabegron for the treatment of OAB. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis of phase III trials were conducted. Four publications involving a total of 5,761 patients were used in the analysis, including four phase III RCTs that compared mirabegron with placebo. We found that mirabegron was effective in treating OAB in our meta-analysis. Co-primary efficacy end points: the mean number of incontinence episodes per 24 h (the standardized mean difference (SMD) = -0.44, 95 % confidence interval (CI) -0.59 to -0.29, p < 0.00001); the mean number of micturitions per 24 h (SMD = -0.62, 95 % CI -0.80 to -0.45, p < 0.00001) and key secondary efficacy end points: mean volume voided per micturition; mean number of urgency episodes per 24 h indicated that mirabegron was more effective than the placebo. Safety assessments included common treatment-emergent adverse events (TEAEs) [OR 1.10, 95 % CI 0.93-1.31, p = 0.25), hypertension, cardiac arrhythmia TEAEs, urinary retention and discontinuations due to adverse event indicated that mirabegron was well tolerated. This meta-analysis indicates that mirabegron to be an effective and safe treatment for OAB symptoms with a low occurrence of side effects. It offers promise as an effective oral agent for the treatment of OAB with a distinct efficacy/tolerability balance.

Mirabegron: A Review of Its Use in Patients with Overactive Bladder Syndrome

Mirabegron (YM178, Myrbetriq™, Betanis(®), Betmiga™) is a β3-adrenergic receptor agonist approved in several countries for the symptomatic treatment of adults with overactive bladder syndrome. In three 12-week, randomized, double-blind, placebo-controlled, multinational trials in patients with overactive bladder syndrome, oral mirabegron 25 or 50 mg once daily significantly reduced the adjusted mean number of incontinence episodes per 24 h (in patients with incontinence at baseline) and the adjusted mean number of micturition episodes per 24 h (in full trial populations) [coprimary endpoints]. Across trials, mirabegron 50 mg once daily also consistently significantly reduced urgency episodes and increased the volume of urine voided per micturition, generally in association with improved health-related quality of life (HR-QOL) and treatment satisfaction. Based on descriptive analyses from a 12-month trial, once-daily mirabegron 50 mg and tolterodine extended-release (ER) 4 mg were both efficacious in reducing urinary symptoms and improving HR-QOL. Mirabegron was generally well tolerated in the trials. Over 12 weeks, the adverse event rate with mirabegron 50 mg once daily was similar to that with placebo. During 12 months of treatment, 2.8 % of mirabegron 50 mg once daily recipients reported dry mouth compared with 8.6 % with tolterodine ER 4 mg once daily recipients. Mirabegron 50 mg once daily carries a low risk of QT interval prolongation. Thus, mirabegron is an efficacious new treatment for overactive bladder syndrome with a favourable tolerability profile.

A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of the β3 Adrenoceptor Agonist, Mirabegron, in Patients With Symptoms of Overactive Bladder

To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB). Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale. Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo. Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo.

Urolastic—A New Bulking Agent for the Treatment of Women with Stress Urinary Incontinence: Outcome of 12 Months Follow Up

Objective. To evaluate the efficacy and safety of the new injectable implant, Urolastic, in women with stress urinary incontinence (SUI) after 12-month followup. Materials and Methods. A prospective, cohort study included adult women with SUI. Patients were treated with Urolastic periurethral injections under local anaesthesia. The injection procedure was repeated after 6 weeks when indicated. Patients were evaluated for efficacy and safety parameters 6 weeks, 3 months, and 12 months after therapy. Results. Twenty women 56 (33–71) years old were included. Thirteen patients (65%) received one injection each (overall average of 2,1 mL); 7 patients (35%) received a second injection. Nineteen patients complete the 12-month followup. The mean Stamey incontinence grade significantly decreased from 1.9 at baseline to 0.4 at 12 months (visit IV) (P < 0.001). None of the patients were dry at baseline; 68% of them were dry at 12 months. The mean number of incontinence episodes significantly decreased from 6/day at baseline to 1.6/day at visit IV (P < 0.001). Reduction in pad weight went from 20.2 to 7.8 g at one year. The mean I-QoL score significantly increased from 51 at baseline to 76 at visit IV (P < 0.001). Six patients (30%) developed minor complications related to the injection procedure. Conclusions. Urolastic is effective and long-standing urethral bulking agent with moderate adverse events.

Efficacy and Tolerability of Mirabegron, a β3-Adrenoceptor Agonist, in Patients with Overactive Bladder: Results from a Randomised European–Australian Phase 3 Trial

BackgroundMirabegron, a β3-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB). ObjectiveTo assess the efficacy and tolerability of mirabegron versus placebo. Design, setting, and participantsMulticenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥18 yr of age with symptoms of OAB for ≥3 mo. InterventionAfter a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4mg orally once daily for 12 wk. Outcome measurements and statistical analysisPatients completed a micturition diary and quality-of-life (QoL) assessments. Co–primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume. Results and limitationsA total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24h (−1.57 [−1.79 to −1.35] and −1.46 [–1.68 to −1.23], respectively, vs placebo −1.17 [−1.39 to –0.95]) and number of micturitions per 24h (−1.93 [−2.15 to −1.72] and −1.77 [−1.99 to −1.56], respectively, vs placebo −1.34 [−1.55 to −1.12]; p<0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment. ConclusionsMirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. Trial identificationThis study is registered at ClinicalTrials.gov, identifier NCT00689104.

Results of a Randomized Phase III Trial of Mirabegron in Patients with Overactive Bladder

Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects. Mirabegron, a β3-adrenoceptor agonist, may offer an effective and well tolerated alternative treatment for overactive bladder. A randomized, double-blind, placebo controlled trial was conducted in the United States and Canada. After a 2-week placebo run-in period, adults with overactive bladder symptoms for 3 or more months were randomized 1:1:1 to receive placebo, 50 or 100 mg mirabegron once daily for 12 weeks. Efficacy data were collected via patient completed diaries and quality of life assessments. Co-primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours. Key secondary micturition and incontinence end points were also evaluated. Safety assessments included treatment emergent adverse events, laboratory assessments, vital signs, electrocardiograms and post-void residual volume. Compared to placebo, 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases (95% CI) from baseline for incontinence episodes (-1.13 [-1.35, -0.91], -1.47 [-1.69, -1.25] and -1.63 [-1.86, -1.40]) and micturitions (-1.05 [-1.31, -0.79], -1.66 [-1.92, -1.40] and -1.75 [-2.01, -1.48]) per 24 hours (p <0.05). Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo. The incidence of frequently reported treatment emergent adverse events (hypertension, urinary tract infection, headache, nasopharyngitis) was similar in the mirabegron and placebo groups. Dry mouth was reported for 1.5%, 0.5% and 2.1% of patients in the placebo, 50 and 100 mg mirabegron groups, respectively. Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects.

Sigmoidocolocystoplasty With Ureteral Reimplantation for Treatment of Neurogenic Bladder

To assess the clinical and urodynamic results of sigmoidocolocystoplasty in patients with neurogenic bladder dysfunction. We retrospectively reviewed 78 augmentation enterocystoplasty cases in our database from 2005 to 2011 to identify 47 patients who had undergone sigmoidocolocystoplasty alone or combined with ureter reimplantation. The indications for surgery and postoperative complications were evaluated. Renal function preservation, increased postoperative bladder capacity, decreased maximal detrusor pressure, and overall patient satisfaction were deemed successful outcomes. The mean follow-up period was 24 months. The mean bladder capacity increased from 160.6 ± 128.3 to 468.5 ± 60.6 mL (P < .001) and the maximal detrusor pressure decreased from 31.1 ± 26.4 to 10.9 ± 4.5 cm H(2)O (P = .002). The serum creatinine level decreased from 270.3 ± 113.6 to 174.4 ± 81.3 μmol/L (P = .001). Most patients resolved the urinary incontinence using clean self-intermittent catheterization. The decrease in the mean number of incontinence episodes and pads used daily indicated a marked improvement in patients' quality of life. Postoperative complications included bowel dysfunction in 5 patients (10.6%), adhesive intestinal obstruction in 4 (8.5%), deteriorating renal function in 3 (6.4%), and vesicoureteral reflux recurrence in 2 patients (4.3%). Nearly all patients expressed satisfaction with the urologic management. Our results suggest that sigmoidocolocystoplasty is safe and effective in treating patients with neurogenic bladder dysfunction. Concomitant ureter reimplantation will be beneficial for patients with a long history of illness.

Mirabegron - a selective β3-adrenoreceptor agonist for the treatment of overactive bladder.

Overactive bladder is a common condition that significantly impacts overall quality of life. Antimuscarinics are the current main pharmacological option for treatment; however, many patients fail to adhere to therapy due to troublesome side effects. Mirabegron is a new beta-3 adrenoreceptor agonist which causes detrusor smooth muscle relaxation and has been proposed to be effective for treating overactive bladder symptoms. Mirabegron has been shown to be superior to placebo for reducing the mean number of incontinence episodes per 24 hours and the mean number of micturitions per 24 hours. Side effects such as dry mouth were observed at similar or lower rates than those seen for placebo and antimuscarinics. Higher doses of mirabegron were associated with minor increases in pulse rate and mean blood pressure. Mirabegron offers a new alternative for treating overactive bladder in patients for which antimuscarinics are either not tolerated or not appropriate.

Mirabegron for the treatment of overactive bladder

Overactive bladder (OAB) syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urge urinary incontinence, in the absence of urinary tract infection or other obvious pathology. Mirabegron (YM-178, Betanis®) is a novel, once-daily, orally active, first-in-class selective β(3)-adrenoceptor agonist that improves symptoms associated with OAB by enhancing storage function and relaxing the urinary bladder. Mirabegron has been approved in Japan for the indication of urgency, urinary frequency and urge urinary incontinence associated with OAB, and was recently submitted for approval to U.S. and European authorities for the same indication. In phase III clinical trials performed in Europe, the U.S. and Australia, mirabegron at doses of 50 or 100 mg for 12 weeks significantly decreased the mean number of incontinence episodes and micturition episodes per 24 hours, and was safe and well tolerated. Mirabegron may be an alternative in patients with OAB who are poor responders to antimuscarinic agents or intolerant of their adverse effects.

A randomized, double‐blind, placebo‐ and propiverine‐controlled trial of the novel antimuscarinic agent imidafenacin in Japanese patients with overactive bladder

To compare the efficacy and tolerability of imidafenacin, a novel antimuscarinic agent, with propiverine and a placebo in Japanese patients with overactive bladder (OAB). Men and women having OAB symptoms were randomized to double-blind treatment with 0.1 mg of imidafenacin twice daily, 20 mg of propiverine once daily, or a placebo for 12 weeks, and assessed for efficacy and safety. Overall, 781 patients were randomized to imidafenacin (324), propiverine (310), or a placebo (147). After 12 weeks of treatment, a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group (P < 0.0001). The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes (P = 0.0014, non-inferiority margin: 14.5%). Imidafenacin was well tolerated. The incidence of adverse events with imidafenacin was significantly lower than with propiverine (P = 0.0101). Dry mouth, the most common adverse event, was significantly more common in the propiverine group than in the imidafenacin group (P = 0.0302). There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval, whereas there was a significant increase in the mean QTc interval in the propiverine group (P < 0.0001), but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups. The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes, and well tolerated for the treatment of OAB symptoms.