Patient‐selected goals in overactive bladder: a placebo controlled randomized double‐blind trial of transdermal oxybutynin for the treatment of urgency and urge incontinence

Study Type – Therapy (RCT)
Level of Evidence 1b What’s k n own on the subject? and What does the study add? In common with other anticholinergics, transdermal oxybutynin improves symptoms, and disease specific quality of life for patients with urgency incontinence. Achievement of patient selected goals for treatment of overactive bladder has also been demonstrated in uncontrolled studies. Over a four week period, transdermal oxybutynin improved urinary urgency for patients with overactive bladder, including those without incontinence. However, in comparison to placebo it did not lead to significant achievement of patients’ own therapeutic goals.

OBJECTIVE

To assess patient selected goal improvement with transdermal oxybutynin, in a representative population of adult women with overactive bladder (OAB).

SUBJECTS AND METHODS

Adult women with ≥3 month history of OAB symptoms, with or without urgency urinary incontinence, were recruited from a tertiary referral urogynaecology unit. Participants were allocated to either transdermal oxybutynin 3.9 mg/day or matching placebo patches in a double‐blind, randomized parallel group design, over 4 weeks. Patient‐selected goal achievement was defined as the primary outcome measure. Participants selected their own goals for treatment at baseline, and subsequently scored achievement of these goals on a visual analogue scale. They completed 3‐day bladder diaries incorporating the Patients Perception of Intensity of Urgency Scale (PPIUS) to assess urgency and urgency incontinence episodes. Quality of life was assessed using the King’s Health Questionnaire (KHQ).

RESULTS

A total of 96 women were randomized; 78 (81.3%) participants completed 4 weeks double‐blind treatment. There was no significant difference between mean goal achievement in the transdermal oxybutynin and placebo groups (41.9% (SD 31.3) vs 32.2% (SD 27.3), P= 0.203). Transdermal oxybutynin was associated with significant improvements in urgency episodes (?1.23 episodes/day (SD1.40) vs ?0.21 episodes/day (SD 1.58), P= 0.01). Both groups made non‐significantly different improvements in KHQ scores; 18 (38.2%) patients in the transdermal oxybutynin group experienced either erythema or pruritus, with 7 (14.9%) experiencing at least one systemic adverse event.

CONCLUSIONS

In women with OAB, in comparison with placebo, transdermal oxybutynin 3.9 mg/day leads to significant objective improvements in urinary urgency, but with no significant difference observed in achievement of patients’ own goals for therapy, or improvement in disease specific quality of life.     

Response to fesoterodine in patients with an overactive bladder and urgency urinary incontinence is independent of the urodynamic finding of detrusor overactivity

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To determine whether the presence of detrusor overactivity (DO) in patients with overactive bladder (OAB) and urgency urinary incontinence (UUI) is a predictor of the response to treatment with fesoterodine.

PATIENTS AND METHODS

This phase 2 randomized, multicentre, placebo‐controlled trial consisted of a 1‐week placebo run‐in phase followed by an 8‐week double‐blind period. Eligible for the study were men and women aged 18–78 years with symptoms or signs of OAB with UUI; they were stratified into two balanced strata depending on the outcome of a baseline urodynamic assessment. By using this particular study design it was possible to investigate whether there were differences between the strata. The primary endpoint was the change from baseline to week 8 in mean voids/24 h. Secondary endpoints were the changes in UUI episodes/week, and for those patients with DO at baseline, the mean changes in volume at first involuntary contraction associated with a feeling of urgency, first desire to void, and strong desire to void, and change in maximum cystometric capacity. Because there were few patients the secondary analyses were considered exploratory.

RESULTS

Overall, there were linear dose‐response relationships for placebo and the fesoterodine groups for the reduction in the number of voids/24 h and UUI episodes/week. Compared with the placebo group, the least squares mean changes from baseline to week 8 in both variables were significantly improved in patients receiving fesoterodine 4 mg (P = 0.045 and 0.040, respectively), 8 mg (P < 0.001 for both), and 12 mg (P < 0.001 for both). There were no significant differences in treatment responses, as measured by both variables between patients with and without DO. For patients with DO, the mean volume at the first desire to void improved in all fesoterodine treatment groups and worsened in the placebo group.

CONCLUSIONS

Regardless of the presence of DO, the response to fesoterodine treatment was dose‐proportional and associated with significant improvements in OAB symptoms, indicating that the response to OAB pharmacotherapy in patients with UUI was independent of the urodynamic diagnosis of DO.     

Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence

A group of authors from the USA evaluated the efficacy and tolerability of tolterodine extended-release on objective and subjective endpoints in men with an overactive bladder. They found that it significantly reduced incontinent episodes and improved patient perception of treatment benefit in men with an overactive bladder OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine extended-release (ER) on objective and subjective endpoints in men with overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND METHODS This was a post hoc analysis of data collected from men with OAB enrolled in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily; tolterodine ER registration trial) and included men with urinary frequency (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes were assessed using 7-day bladder diaries. Patient perception of treatment benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded throughout the study. RESULTS: In all, 163 men with OAB (placebo, 86; tolterodine ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical characteristics were similar for the two treatment groups. Compared with placebo, tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving tolterodine ER had fewer micturitions/24 h, but this was not a significant difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly more men treated with tolterodine-ER (63%) than placebo-treated men (46%) reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs 7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms suggestive of urinary retention that led to his withdrawal from the study. None of the men had acute urinary retention requiring catheterization. CONCLUSION: In men with OAB and urgency UI, tolterodine ER was well tolerated and significantly reduced episodes of urgency UI, and improved patient perception of treatment benefit.     

Urinary urgency outcomes after propiverine treatment for an overactive bladder: the ‘Propiverine study on overactive bladder including urgency data’

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To investigate the effects of a daily regimen of propiverine 20 mg in patients with an overactive bladder (OAB), focused on improving urgency, as the clinical efficacy of treatment for OAB should be measured in terms of urgency, the cornerstone symptom of OAB.

PATIENTS AND METHODS

Eligible patients aged ≥18 years with symptoms of OAB were enrolled in this multicentre, prospective, parallel, double‐blind, placebo‐controlled trial. Of 264 patients (mean age 52.2 years), 221 who had efficacy data available from baseline and at least one on‐treatment visit with >75% compliance with medication were analysed (142 in the propiverine group and 79 in the placebo group). All patients were randomized to receive a placebo or 20 mg propiverine once daily in a 12‐week study. They completed a 3‐day voiding diary before visits during the study period, including the severity of urgency associated with every voiding, using the Indevus Urgency Severity Scale and the Urgency Perception Score. The patients’ overall self‐evaluation of treatment benefits at the end of the study, and safety data, were also collected.

RESULTS

The daily urgency episodes reduced significantly from baseline to 12 weeks on propiverine treatment, compared with placebo (?46.0% vs ?31.3%, P = 0.005). Secondary endpoints, including sum of urgency severity per 24 h, urgency severity per void, and daytime voiding frequency, were also improved significantly in the propiverine group. Overall, of those patients treated with propiverine, 38.7% rated their treatment as providing ‘much benefit’, compared with 15.2% of the placebo group (P = 0.025). Adverse events reported by 32 (22.5%) and 10 (12.7%) patients in the propiverine and placebo group were all tolerable. However, this is a short‐term study using only one fixed regimen.

CONCLUSIONS

Propiverine 20 mg once‐daily could be an effective treatment for patients with OAB, by improving urgency.     

Propiverine hydrochloride in Japanese patients with overactive bladder: A randomized,double‐blind,placebo‐controlled trial

Objectives: The aim of this study was to investigate the efficacy and safety of propiverine for overactive bladder (OAB) in Japanese patients. Methods: In this multicentre, randomized, double‐blind study, patients ≥20 years old with symptoms of OAB for ≥12 weeks were allocated to either propiverine (20 mg once daily) or placebo for 12 weeks. Efficacy and quality of life were assessed using a 7‐day bladder diary, the OAB symptom score, and King's Health Questionnaire. Safety was mainly assessed by adverse events and the QTc interval. Results: A total of 567 patients were allocated. Change in number of micturitions/24 h was significantly greater in the propiverine group than in the placebo group (–1.86 vs?1.36, P = 0.001). Compared to placebo, propiverine produced significant improvements in urgency, urgency incontinence, urine volume/micturition, and the OAB symptom score. Significant improvements in urgency, urgency incontinence, and micturition frequency were observed at the first 4 weeks of treatment. All nine domains of King's Health Questionnaire were improved more with propiverine than with placebo. Adverse effects with propiverine were mostly mild, and no patient developed QTc interval prolongation exceeding 500 ms. Conclusion: Propiverine is effective for Japanese OAB patients by improving their symptoms and quality of life with a predictable side‐effect profile.     

Solifenacin in the treatment of urgency and other symptoms of overactive bladder: results from a randomized, double-blind, placebo-controlled, rising-dose trial

OBJECTIVES

To examine the effects of the antimuscarinic agent solifenacin on urinary urgency, using a range of novel and established outcome measures, as urgency is the principal symptom of the overactive bladder syndrome (OAB).

PATIENTS AND METHODS

The study (SUNRISE, solifenacin in the treatment of urgency symptoms of OAB in a rising dose, randomized, placebo‐controlled, double‐blind, efficacy trial) was a randomized, double‐blind, 16‐week, placebo‐controlled, multicentre study of solifenacin 5/10 mg in 863 patients with symptoms of OAB for ≥3 months. The primary efficacy variable was the change from baseline to endpoint in the number of episodes of severe urgency with or without urgency incontinence per 24 h, as measured using the Patient Perception of Intensity of Urgency Scale, grade 3 + 4. Secondary efficacy variables included patient‐reported outcomes for bladder condition, urgency bother and treatment satisfaction. A 3‐day voiding diary was used to record micturition frequency and episodes of urgency and incontinence. A 7‐day diary was used to assess speed of onset of effect.

RESULTS

Solifenacin 5/10 mg was significantly more effective than placebo in reducing the mean number of episodes of severe urgency with or without incontinence per 24 h from baseline to endpoint (?2.6 vs ?1.8, P < 0.001). There were also statistically significant differences in favour of solifenacin 5/10 mg over placebo for all secondary variables measured at endpoint, including patient‐reported outcomes. There was a significant improvement in urgency as early as day 3 of treatment. Treatment‐emergent adverse events with solifenacin 5/10 mg were mainly mild or moderate in severity, and only led to discontinuation in 3.6% of patients.

CONCLUSION

Solifenacin significantly reduced the number of urgency episodes and the extent of urgency bother, and was well tolerated; it was effective as early as day 3 of treatment.     

Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? Few prevalence studies used current ICS LUTS symptom definitions and to our knowledge no studies exist that estimate total worldwide prevalence of reported LUTS symptoms. One of the primary goals of this analysis was to estimate current and future worldwide prevalence of LUTS among adults. Our estimation model suggests that LUTS are highly prevalent worldwide, with an increasing burden predicted over time.

OBJECTIVE

? To estimate and predict worldwide and regional prevalence of lower urinary tract symptoms (LUTS), overactive bladder (OAB), urinary incontinence (UI) and LUTS suggestive of bladder outlet obstruction (LUTS/BOO) in 2008, 2013 and 2018 based on current International Continence Society symptom definitions in adults aged ≥20 years.

PATIENTS AND METHODS

? Numbers and prevalence of individuals affected by each condition were calculated with an estimation model using gender‐ and age‐stratified prevalence data from the EPIC study along with gender‐ and age‐stratified worldwide and regional population estimates from the US Census Bureau International Data Base.

RESULTS

? An estimated 45.2%, 10.7%, 8.2% and 21.5% of the 2008 worldwide population (4.3 billion) was affected by at least one LUTS, OAB, UI and LUTS/BOO, respectively. By 2018, an estimated 2.3 billion individuals will be affected by at least one LUTS (18.4% increase), 546 million by OAB (20.1%), 423 million by UI (21.6%) and 1.1 billion by LUTS/BOO (18.5%). ? The regional burden of these conditions is estimated to be greatest in Asia, with numbers of affected individuals expected to increase most in the developing regions of Africa (30.1–31.1% increase across conditions, 2008–2018), South America (20.5–24.7%) and Asia (19.7–24.4%).

CONCLUSIONS

? This model suggests that LUTS, OAB, UI and LUTS/BOO are highly prevalent conditions worldwide. Numbers of affected individuals are projected to increase with time, with the greatest increase in burden anticipated in developing regions. ? There are important worldwide public‐health and clinical management implications to be considered over the next decade to effectively prevent and manage these conditions.     

One‐year results with selective bladder denervation in women with refractory overactive bladder

Aims : To report 1‐year results with selective bladder denervation (SBD) of the trigone in women with refractory overactive bladder (OAB). Methods : In this prospective, international, multicenter case series, women with refractory OAB underwent a single SBD treatment of the bladder subtrigone region using temperature‐controlled radiofrequency. Patients were followed for 1 year and evaluated for changes in OAB symptoms and adverse events. Results : Among 35 women, 29 (83%) returned for 1‐year follow up. Median symptom reductions based on 3‐day bladder diaries were 68% for urgency urinary incontinence ( P < .001), 67% for urinary incontinence ( P < .001), 43% for urgency episodes ( P < .001), 5% for urinary frequency ( P = .19), and 33% for the total urgency and frequency score ( P < .001), with the majority of treatment benefit realized in the first month. Treatment benefit was reported in 72% of patients, the clinical success rate (≥50% reduction in urgency urinary incontinence) was 69%, and the dry rate was 10%. Statistically significant improvements occurred on Symptom Bother and Health‐related Quality of Life scales on the Overactive Bladder questionnaire, and on 6 of 9 King's Health Questionnaire domains. Patients with less severe baseline symptoms had similar quality of life improvements as those with more severe baseline symptoms. Device‐ or procedure‐related adverse events were reported in 6 (17%) patients. Conclusions : A single treatment with selective bladder denervation is durable for 1‐year in a significant proportion of women with refractory overactive bladder.     

Tolterodine ER reduced increased bladder wall thickness in women with overactive bladder. A randomized,placebo‐controlled,double‐blind,parallel group study

Aims

We evaluated the effect of Tolterodine extended release (TER) versus placebo on bladder wall thickness (BWT) using transvaginal ultrasound in women with overactive bladder (OAB).

Materials and Methods

We recruited 79 women with symptoms of OAB with a mean age of 47 years who had a BWT of at least 5 mm and a post‐micturition volume of less than 50 mL at screening. Subjects received TER 4 mg or placebo once daily for the first 12 weeks of the study. For the subsequent 12 weeks, all subjects received TER 4 mg once daily. BWT was measured at screening, weeks 12 and 24. Subjects recorded number of micturitions, incontinence episodes and urgency episodes, and volume voided per micturition at regular intervals during the study.

Results

Treatment with TER for 12 weeks produced a statistically significant decrease from baseline in BWT (mean [SD] = 0.9 [1.4] mm; P < 0.05) that was not evident following treatment with placebo (0.2 [1.6] mm; P = 0.54). However, the treatment difference did not reach statistical significance (LS Mean = ?0.4; 95%CI: ?1.2, 0.3; P = 0.25). After 12 weeks of treatment, subjects who had taken TER showed an improvement in each bladder diary variable compared to placebo‐treated subjects.

Conclusions

TER may have a direct effect on BWT in women with OAB. Larger studies are warranted to further investigate the effect of behavioral interventions and antimuscarinics, such as TER, on BWT in women with OAB and increased BWT.