Search

Purpose: The efficacy and safety of vibegron, a β 3 -adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial., Materials and Methods: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs)., Results: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%)., Conclusions: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

Purpose: The long-term safety, tolerability and efficacy of vibegron in adults with overactive bladder were evaluated in the 40-week phase 3 EMPOWUR extension study., Materials and Methods: Patients who completed 12 weeks of once-daily vibegron 75 mg or tolterodine 4 mg extended release in EMPOWUR continued double-blind treatment; patients who completed 12 weeks of placebo were randomly assigned 1:1 to receive double-blind vibegron or tolterodine. The primary outcome was safety, measured by incidence of adverse events. Secondary outcomes included change from baseline at week 52 in average daily number of micturitions and urgency episodes (all patients), and urge and total urinary incontinence episodes (patients with overactive bladder wet) based on 7-day diary data., Results: Of 506 patients randomized 505 received ≥1 dose of medication, and 430 (85%) completed the study. A total of 12 patients (2.4%) discontinued owing to adverse events. The most common adverse events with vibegron/tolterodine (>5% in either group) were hypertension (8.8%/8.6%), urinary tract infection (6.6%/7.3%), headache (5.5%/3.9%), nasopharyngitis (4.8%/5.2%) and dry mouth (1.8%/5.2%). Improvements in efficacy end points were maintained for patients receiving vibegron for 52 weeks; least squares mean change from baseline to week 52 in micturitions was ‒2.4 for vibegron vs ‒2.0 for tolterodine; in urge urinary incontinence episodes ‒2.2 vs ‒1.7 (p <0.05); in urgency episodes ‒3.4 vs ‒3.2; and in total incontinence episodes ‒2.5 vs ‒1.9 (p <0.05). Among patients with overactive bladder wet 61.0% receiving vibegron experienced ≥75% reduction in urge urinary incontinence episodes after 52 weeks of treatment vs 54.4% with tolterodine, while 40.8% vs 34.2% experienced a 100% reduction., Conclusions: Vibegron demonstrated favorable long-term safety, tolerability and efficacy in patients with overactive bladder, consistent with results of the 12-week study.

Purpose: We assessed efficacy, safety and tolerability of vibegron, a novel, potent, highly selective β 3 -adrenoceptor agonist, administered 12 weeks at 75 mg once daily to patients with overactive bladder in an international phase III trial with placebo and active control., Materials and Methods: Adult patients with overactive bladder with 8.0 or more micturitions per day were randomized 5:5:4 to 75 mg vibegron, placebo or extended-release 4 mg extended-release tolterodine. Up to 25% of patients could have dry overactive bladder (less than 1.0 urge incontinence episode per day). Patients completed 7-day voiding diaries at baseline and weeks 2, 4, 8 and 12., Results: Of 1,518 randomized patients 90.4% completed the trial. At 12 weeks micturitions decreased by an adjusted mean of 1.8 episodes per day for vibegron vs 1.3 for placebo (p <0.001, co-primary end point) and 1.6 for tolterodine. Among incontinent patients urge incontinence episodes decreased by an adjusted mean 2.0 episodes per day for vibegron vs 1.4 for placebo (p <0.0001, co-primary end point) and 1.8 for tolterodine. Moreover, vibegron was statistically significantly superior to placebo for key secondary measures of number of urgency episodes, volume per micturition and proportion of incontinent patients with a 75% or greater reduction in urge incontinence episodes (all p <0.01). Among vibegron treated patients 1.7% discontinued treatment because of adverse events vs 1.1% for placebo and 3.3% for tolterodine. Incidence of hypertension was 1.7% for vibegron and for placebo., Conclusions: Once daily 75 mg vibegron provided statistically significant reductions in micturitions, urgency episodes and urge incontinence, and increased the volume per micturition. Treatment was well tolerated with a favorable safety profile.

Purpose: PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia., Materials and Methods: In this phase 4 study a 4-week 0.4 mg tamsulosin run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received 25 mg mirabegron or placebo add-on therapy. At 4 weeks doses were titrated to 50 mg mirabegron or placebo equivalent. Efficacy end points were changes from baseline to end of treatment in mean number of micturitions per day (primary), mean volume voided per micturition, number of urgency episodes per day, total urgency and frequency score, and total International Prostate Symptom Score (secondary). Safety assessments included treatment emergent adverse events, and post-void residual volume, and maximum urinary flow measurements., Results: Of the 676 men most were 65 years old or older (380, 56.2%). Tamsulosin plus mirabegron was statistically superior to tamsulosin plus placebo in reducing the mean number of micturitions per day (-2.00 vs -1.62; adjusted difference -0.39; 95% CI -0.76, -0.02). Statistically superior results were noted for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score (not International Prostate Symptom Score). Higher overall treatment emergent adverse event rates were observed with tamsulosin plus placebo, although higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. Urinary retention rates were higher in the tamsulosin plus mirabegron group. Post-void residual volume and maximum urinary flow results were not clinically meaningful., Conclusions: The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with overactive bladder symptoms receiving tamsulosin for benign prostatic hyperplasia.

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusions: 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.

Purpose: To our knowledge there is no index in urology that yields a single, quantifiable and clinically interpretable measure of overactive bladder (OAB) symptoms, including urgency, 24-hour voiding frequency and urge urinary incontinence (UUI). Urgency is the most difficult of these symptoms to measure. The Indevus Urgency Severity Scale (Indevus Pharmaceuticals, Lexington, Massachusetts) was recently developed and validated to capture urgency severity per toilet void. The scale has been combined with 24-hour frequency and UUI episodes to create the OAB Symptom Composite Score (OAB-SCS). We present this composite score., Materials and Methods: Two multicenter trials were performed to determine the effects of trospium chloride given as 20 mg tablets vs placebo. A total of 1,157 patients, including 581 who received placebo and 576 who received trospium, were randomly assigned to treatment. Daily OAB-SCS totals were obtained for each patient for each day during the 7-day diary collection period for every visit., Results: The average baseline OAB-SCS value was 36. The mean change from baseline in the trospium and placebo groups was 5 and 1 OAB-SCS points in patients with mild OAB, 10 and 5 in patients with moderate OAB, and 13 and 9 in patients with severe OAB, respectively., Conclusions: The OAB-SCS discriminated between placebo and pharmacologically treated (trospium chloride) patients with OAB in this study. The OAB-SCS is an improvement over individual symptoms alone. It is easy to implement and interpret and it will prove to be a clinically relevant tool in clinical trials in which patient diary data are captured.

Purpose: We identify a provocative maneuver to enhance the sensitivity of cystometry in detecting detrusor instability when urge incontinence is suspected based on clinical history., Materials and Methods: A total of 134 consecutive women with clinical urge incontinence underwent carbon dioxide cystometry between August 1995 and October 1996. The bladder was filled to maximal capacity with the patient supine. Six provocative maneuvers were performed consecutively to evoke detrusor instability, including lying supine, rising to a seated position, walking toward the bathroom, handwashing, coughing and sitting on the toilet with instructions not to void. Subjects were divided into 2 groups depending on the order of maneuvers. Sitting on the toilet was the last maneuver for group 1 (80 patients) and was in the middle of the sequence for group 2 (54)., Results: Sitting on the toilet evoked detrusor instability in 37.5% of group 1 and 53.8% of group 2. This maneuver with instructions not to void was the most provocative stimulus in eliciting detrusor instability with a detection rate of 68.4% for all subjects., Conclusions: Sitting on the toilet with the bladder at maximal capacity is the most provocative maneuver for detecting detrusor instability. The incidence of suspected detrusor instability is enhanced by using this test during routine cystometry.

To our knowledge we report the first case of bladder perforation in a patient with no history of pelvic surgery or delivery. The patient presented 3 days post partum with renal failure and ascites. Paracentesis and cystography confirmed urinary ascites and bladder rupture. After open bladder repair convalescence was uneventful. The literature on intraperitoneal bladder rupture and urinary ascites is reviewed.

Extended voiding cystometry was performed to elucidate the true detrusor function in a patient originally misdiagnosed during standard fill cystometry. This methodology allows for observation of an extended period of bladder activity and eliminates the artifacts of classical fill cystometry, which are detrusor instability and noncompliance. A chronically elevated intravesical pressure between contractions (inter-contraction pressure) representing high pressure residual urine, as well as frequent, high amplitude, long duration detrusor contractions during the storage phase and a large post-void residual urine volume were documented. These urodynamic abnormalities are known to precipitate hydroureteronephrosis in the absence of vesicoureteral reflux.

A retrospective urodynamic study of 50 parkinsonian patients was done to determine the incidence and causes of post-prostatectomy incontinence. At presentation 22 per cent of the patients were incontinent. In 36 patients who underwent transurethral prostatectomy the incontinence rate was 17 per cent preoperatively and 28 per cent postoperatively. There was a clear association between normal voluntary sphincter control and urinary continence. After transurethral prostatectomy 5 of 6 patients continent preoperatively (83 per cent) who had abnormal sphincter control became incontinent compared to 1 of 24 (4.2 per cent) who had normal sphincter control. We conclude that the major risk of incontinence following prostatectomy in the parkinsonian patient is associated with lack of voluntary sphincter control.

The clinical presentation of incontinence was compared to diagnoses based on urological and urodynamic evaluation in 135 elderly women assessed consecutively in an outpatient clinic. Most patients (64 per cent) presented with mixed symptoms: 16 per cent presented with pure stress and 16 per cent with pure urge incontinence. After evaluation 46 per cent of the patients had stress incontinence with a stable bladder, 27 per cent had detrusor instability or hyperreflexia without sphincter weakness and 19 per cent had mixed urodynamic abnormalities. Presenting symptoms were predictive of urodynamic diagnosis in 64 per cent of the patients with pure stress incontinence and 55 per cent with pure urge incontinence. In general, symptoms in our patient population were less predictive of urodynamic findings than in previously reported series of younger incontinent women but they were more predictive than in other series of elderly women. Predictive values for some urodynamic findings were enhanced by combining a symptom with certain physical findings. Implications of these data for the evaluation and treatment of incontinence in the geriatric population are discussed.

Bladder capacity and stability were determined among 171 incontinent geriatric patients (mean age 80 years) with 2 techniques: a simple procedure for cystometry involving incremental bladder filling by gravity and a continuous water filling multichannel cystometrogram. Bladder capacities measured by both methods in 164 patients were correlated significantly by simple linear regression (r equals 0.75, p equals 0.0001) and they were not significantly different by paired t tests (t equals 1.20, p equals 0.23). Of the patients 110 (64 per cent) had detrusor motor instability or hyperreflexia on the multichannel cystometrogram, and simple cystometry had a sensitivity of 75 per cent, specificity of 79 per cent and positive predictive value of 85 per cent for this finding. The simple procedure was practical, well tolerated and helped to provide information for management decisions that would have been difficult to obtain from many of these geriatric patients without a formal and more complex urodynamic evaluation. When performed with other simple tests of lower urinary tract function and interpreted in conjunction with a few straightforward clinical criteria, simple cystometry can be helpful to assess bladder function among incontinent geriatric patients in settings in which formal urodynamics are either unavailable or impractical.

Severe urinary tract complications secondary to a chronic indwelling contraceptive diaphragm are described in a patient who presented with urinary incontinence.