Management Of Idiopathic Overactive Bladder Research Articles

Oral phenazopyridine vs intravesical lidocaine for bladder onabotulinumtoxinA analgesia: a randomized controlled trial

The efficacy of intradetrusor onabotulinumtoxinA injections for the management of idiopathic overactive bladder has been well-established. The injections are typically performed in the office setting using local analgesia, most commonly a 20 to 30-minute intravesical instillation of lidocaine. There are limited data evaluating alternative bladder analgesics. To compare pain scores with preprocedure oral phenazopyridine vs intravesical lidocaine in women undergoing intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder. Nonpregnant adult females with idiopathic overactive bladder, scheduled for office injection of 100 units of intradetrusor onabotulinumtoxinA were randomized to either 200 mg of oral phenazopyridine taken 1 to 2 hours preprocedure or a 20-minute preprocedure intravesical instillation of 50 mL of 2% lidocaine. We excluded participants with neurogenic bladders, and those who had received intradetrusor onabotulinumtoxinA injections in the previous 12 months. The primary outcome was pain measured by a 100-mm visual analog scale. Demographic characteristics and overall satisfaction with the procedure were also recorded. Providers answered questions about cystoscopic visualization, ease of procedure, and perception of participant comfort. Prespecified noninferiority margin was set to equal the anticipated minimum clinically important difference of 14 mm. A planned sample of 100 participants, 50 in each treatment arm, provided 80% power to detect noninferiority at a significance level of.05. We performed a modified intention-to-treat analysis and compared variables with the t test or the Fisher exact test. A total of 111 participants were enrolled, and complete data were obtained for 100 participants; 47 participants were randomized to phenazopyridine and 53 to lidocaine. Baseline characteristics did not differ between groups. There were 19.6% and 20.8% of participants in the phenazopyridine and lidocaine groups, respectively, who previously underwent intradetrusor onabotulinumtoxinA injections. The mean postprocedure pain was 2.7 mm lower in the phenazopyridine group than in the lidocaine group (95% confidence interval,-11.3 to 10.7), demonstrating noninferiority. More than 90% of participants in both groups stated that the pain was tolerable. Slightly more participants reported being "very satisfied" in the lidocaine group, although this was not statistically significant (50.0% vs 40.4%; P=.34). Providers reported clear visualization in 89.4% of participants in the phenazopyridine group and in 100% of participants in the lidocaine group (P=.02). Provider perception of participant comfort and overall ease of procedure were not different between groups. Length of time in the exam room was significantly shorter in the phenazopyridine than in the lidocaine group (44.4 vs 57.5 minutes; P=.0003). In women receiving intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder, oral phenazopyridine was noninferior to intravesical lidocaine for procedural pain control. Phenazopyridine is well-tolerated by participants, allows for the procedure to be performed with similar ease, and is associated with shorter appointment times.

Outcome reporting in randomized controlled trials (RCTs) on the pharmacological management of idiopathic overactive bladder (OAB) in women; a systematic review for the development of core outcome sets (COS)

Introduction and hypothesisEvidence on OAB management remains suboptimal and methodological limitations in randomized control trials (RCTs) affect their comparability. High quality meta-analyses are lacking. This study aimed to compare selection and reporting of outcomes and outcome measures across RCTs as well as evaluate methodological quality and outcome reporting quality as a first stage in the process of developing core outcome sets (COS).MethodsRCTs were searched using Pubmed, EMBASE, Medline, Cochrane, ICTRP and Clinicaltrials.gov from inception to January 2020, in English language, on adult women. Pharmacological management, interventions, sample size, journal type and commercial funding were documented. Methodological and outcome reporting quality were evaluated using JADAD and MOMENT scores.ResultsThirty-eight trials (18,316 women) were included. Sixty-nine outcomes were reported, using 62 outcome measures. The most commonly reported outcome domains were efficacy (86.8%), safety (73.7%) and QoL (60.5%). The most commonly reported outcomes in each domain were urgency urinary incontinence episodes (UUI) (52.6%), antimuscarinic side effects (76.3%) and change in validated questionnaire scores (36.8%).A statistically significant correlation was found between JADAD and MOMENT (Spearman’s rho = 0.548, p < 0.05) scores. This indicates that higher methodological quality is associated with higher outcome reporting quality.ConclusionsDevelopment of COS and core outcome measure sets will address variations and lead to higher quality evidence. We recommend the most commonly reported outcomes in each domain, as interim COS. For efficacy we recommend: UUI episodes, urgency and nocturia episodes; for safety: antimuscarinic adverse events, other adverse events and discontinuation rates; for QoL: OAB-q, PPBC and IIQ scores.

Contemporary Landmark Trials Update in the Management of Idiopathic Overactive Bladder

The landmark trials evaluating the different lines of treatment for overactive bladder (OAB) were reviewed to provide a summary of the most recent advances in behavioral, medical, and surgical management of OAB in the last 5 to 10 years. Clinical trials for the treatment of OAB have evaluated the efficacy and effectiveness of different combinations of medical management, surgical management, and conservative therapies in quality of life improvement in these patients. All three lines of therapy include safe and effective treatment options that can be used as monotherapy or in combination to treat a variety of patient characteristics and comorbidities. The three lines of treatment currently available to patients continue to be improved with new innovations in strategies for their use in combination with one another and improving technology to make them safer, more effective, and individualized to each patient’s needs.

Onabotulinum toxin-A versus extended release tolterodine in the management of idiopathic overactive bladder in children: A pilot randomised controlled trial (OVERT trial)

Idiopathic Overactive Bladder is the most common cause of urinary incontinence in children. Anticholinergic medications are successful in only 20% of those with daily wetting so there is a real need to find a more effective treatment for this condition. Onabotulinum toxin A injections are often used as a treatment but there have been no randomised controlled trials investigating effectiveness in children. To provide information that would inform the design and conduct of a definitive trial comparing onabotulinum toxin A with extended-release tolterodine for the management of therapy resistant idiopathic overactive bladder in children. Specific objectives were to assess rates of eligibility, recruitment, acceptability of randomisation, loss to follow-up, acceptability of urodynamic assessment and obtain primary outcome data for sample size estimation. Single-centre, parallel, two-arm, open-label pilot randomised controlled trial. Eligible patients (aged 7-16 years) were recruited at Royal Manchester Children's Hospital and randomised (1:1) using a web-based system. EudraCT 2014-001068-36; Funding: UK NIHR Research for Patient Benefit Programme. 98 patients were assessed for eligibility, 85 (87%) were eligible for screening, parents of 62 (73%) provided consent, 46 (74%) remained eligible and were randomised (onabotulinum=22, tolterodine=24). All participants commenced allocated treatment. Two patients withdrew from follow-up. All participants underwent urodynamic assessment at baseline and 35 (76%) additionally at week 6. The mean (standard deviation) number of wetting episodes per day at week 6 was 1.4 (1.7) in the onabotulinum group and 1.6 (1.0) in the tolterodine group. There was one serious adverse event (probably related to the drug) and 22 non-serious adverse events reported by 8 participants in the onabotulinum group (36%). There were 23 non-serious adverse events reported by 9 participants in the tolterodine group (38%). Recruitment was challenging but eligibility and consent rates were high as were retention rates. Treatment compliance in the botox group was high but it was difficult to measure in the tolterodine group. Treatment switching was also an issue. Recruitment to a definitive trial was demonstrated to be feasible if a large number of centres are involved, though further consideration is required regarding trial design.

Long-term follow-up reveals a low persistence rate of abobotulinumtoxinA injections for idiopathic overactive bladder

Little is known about long-term efficacy and tolerance of intra-detrusor injections of abobotulinumtoxinA for management of idiopathic overactive bladder (OAB). We report long-term efficacy and compliance of abobotulinumtoxinA in patients treated for OAB. All patients treated with abotulinumtoxinA for OAB in a tertiary reference centre between 2005 and 2012 were included in a retrospective analysis. Patients received 150, 250 or 500 U of abotulinumtoxinA as first injection. The primary endpoint was the discontinuation rate at 5 years. Other outcomes of interest were: rate of failure, reasons for discontinuation and subsequent treatment elected in those who did not persist with abobotulinumtoxinA. Fifty-nine patients (50 women and 9 men) were included. Forty-one patients (69.4%) received 250 U of abobotulinumtoxinA as first injection. Thirteen patients (22%) received 500 U and 5 (8.4%) received 150 U of BoNT-A. Median follow-up was 83.6 months [0.3-183.6]. Median number of injections per patient was 2 [1-15] and median reinjection interval was 10.7 [3-86.4] months. The estimated 5-year discontinuation-free survival rate was 23.4%. Fourteen patients (23.7%) experienced persistent improvement of symptoms and 12 patients (20.3%) stopped the injections because of tolerability issues. Main cause of discontinuation was primary failure, which occurred in 21 patients (35.5%). Overall, 59.3% of patients were successfully treated with first abobotulinumtoxinA injection. Although the estimated 5-year discontinuation-free survival rate is low, abobotulinumtoxinA could be considered as an alternative off-labelled in patients not responders to onabotulinumtoxinA after failure of other conservative measures. 3.

Efficacy and tolerance of botulinum toxin injections after sacral nerve stimulation failure for idiopathic overactive bladder.

Management of idiopathic overactive bladder (iOAB) after the failure of sacral nerve modulation (SNM) is very challenging. To the best of our knowledge, no study has evaluated the use of botulinum toxin A (BoNT-A) after SNM failure for iOAB. The aim of this study is to evaluate the tolerance and efficacy of BoNT-A injection after the failure of SNM for iOAB. We conducted a retrospective multicentric analysis of all patients who had received either onabotulinumtoxinA or abobotulinumtoxinA intradetrusor injection for iOAB after SNM failure, between January 2004 and December 2017. The primary outcome was the percentage of success of first BoNT-A injection (either resolution of their urinary incontinence or their frequency or more than 50% reduction in frequency). Secondary outcomes were results of urodynamic studies, complications, total number of injections, causes of withdrawal, and subsequent treatment. Seventy-six patients (62 female) were included. The percentage of success of first BoNT-A injection was 43.4% (n = 33). All overactive bladder symptoms were significantly improved on the 3-day bladder diary. Twenty-eight patients (36.8%) were put under clean intermittent self-catheterization transitory. After a mean follow-up of 57.7 (±38.5) months, median number of injections was 2 (1-15). Overall, 42 patients (55.2%) stopped injections during follow-up. The estimated 36-months discontinuation-free rate was 48.1%. Mean cause of discontinuation was a primary failure (n = 32; 42.1%). BoNT-A can be used in SNM nonresponders with a success rate of 43.4% but is associated with a high long-term discontinuation rate.

Impact of urodynamic evaluation on the treatment of women with idiopathic overactive bladder: a systematic review.

Overactive bladder (OAB) is a common clinical condition affecting women. The impact of urodynamics (UDS) on the management of idiopathic OAB in women is highly debated. This systematic review analyzes the impact of UDS on the choice and on the outcomes of treatment of female idiopathic OAB. A systematic literature search in the PubMed/Medline, Web of Science, Scopus and Cochrane databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement to identify clinical trials, randomized controlled trials, meta-analyses, and guidelines on female OAB and UDS published from 2000. A total of 1554 records were initially identified and 12 articles were included in the final qualitative synthesis. UDS represents the main tool to diagnose detrusor overactivity (DO) in OAB female patients which is considered one of the major OAB underlying pathophysiology factor. UDS can underline the presence of voiding dysfunction that could be considered as another underlying cause of uncomplicated female OAB. On the basis of this urodynamic findings, we can better define different aspects of OAB syndrome leading to a more tailored and proper treatment. UDS can have a useful role in the diagnosis of idiopathic OAB in women given the possibility to gain a precise diagnosis and, therefore, a tailored treatment based on the underlying cause. The integration of clinics with UDS and all the other diagnostic available tools is desirable.

Current pharmacological management of idiopathic overactive bladder in children in the UK: a national survey of practice

Children with daytime urinary incontinence secondary to idiopathic overactive bladder (IOAB) commonly present to paediatric urologists following failure of standard urotherapy and/or 1st-line anticholinergics. Off-label oral medications and intravesical botulinum toxin A (BtA) are being increasingly used for treatment-refractory IOAB, despite the paucity of high-quality evidence and guidelines. Knowledge of contemporary paediatric urologists' practice allows specialists to keep up-to-date with current trends in the management of IOAB in children. 1. To present an analysis of contemporary tertiary management of IOABin children and 2. to highlight current trends in practice and identify areas of high variability in care for targeted research. Paediatric urologists (55 individuals) who attended the 2018 national British Association of Paediatric Urologists (BAPU) congress responded to a 20-question survey presented at the congress. Respondents could submit one answer per question, and one survey was taken per respondent, using secure software to disable any manipulation. Answers were analysed prospectively by a single reviewer. Of UK paediatric urologists, 98% regularly manage children with IOAB, 48% use 48-hfrequency/volume charts and others use three or seven-day bladder diaries to aid diagnosis. Oxybutynin is the 1st-line therapy for 85%, 2nd-line is tolterodine (53%), and 3rd-line is solifenacin (41%). Mirabegron is used either alone or in combination with solifenacin as 4th-line management by 55%. Those who use intravesical Botulinum toxin A (BtA) accounted for 81% and 84% of these perform invasive urodynamic assessment prior to BtA administration. Post-BtA, assessment was clinical in 18%, 24% use invasive urodynamics, whereas uroflowmetry is preferred by 58%. Of the paediatric urologists, 72% believe the most clinically significant outcome of treatment is patient-reported improvement. Treatment success is defined variably: 49% define success as completely dry, whereas 35% accept a 90% improvement as success. Off-label medications are being used widely either alone or in combination by paediatric urologists. In oral therapy-resistant IOAB, BtA is being used by the majority of specialists, usually after formal urodynamic assessment. However, post-BtA assessment and evaluation of treatment success for IOAB are variable.

OnabotulinumtoxinA in the treatment of overactive bladder: a cost-effectiveness analysis versus best supportive care in England and Wales.

The cost-effectiveness of onabotulinumtoxinA (BOTOX(®)) 100U+best supportive care (BSC) was compared with BSC alone in the management of idiopathic overactive bladder in adult patients who are not adequately managed with anticholinergics. BSC included incontinence pads and, for a proportion of patients, anticholinergics and/or occasional clean intermittent catheterisation. A five-state Markov model was used to estimate total costs and outcomes over a 10-year period. The cohort was based on data from two placebo-controlled trials and a long-term extension study of onabotulinumtoxinA. After discontinuation of initial treatment, a proportion of patients progressed to downstream sacral nerve stimulation (SNS). Cost and resource use was estimated from a National Health Service perspective in England and Wales using relevant reference sources for 2012 or 2013. Results showed that onabotulinumtoxinA was associated with lower costs and greater health benefits than BSC in the base case, with probabilistic sensitivity analysis indicating an 89% probability that the incremental cost-effectiveness ratio would fall below £20,000. OnabotulinumtoxinA remained dominant over BSC in all but two scenarios tested; it was also economically dominant when compared directly with SNS therapy. In conclusion, onabotulinumtoxinA appears to be a cost-effective treatment for overactive bladder compared with BSC alone.

Botulinum Toxin-A Injections for Idiopathic Overactive Bladder: A Systematic Review and Meta-Analysis

Objective: To review the current evidence on the efficacy and safety of botulinum toxin-A in the management of idiopathic overactive bladder (OAB). Methods: A systematic search of PubMed, Embase and the Cochrane Central Search Library was performed. All randomized controlled trials comparing botulinum toxin-A with placebo, different doses and injection techniques, in patients with idiopathic OAB was included. The analyzed outcomes were quantification of symptoms, urodynamic outcomes, quality of life and adverse events. Result: A total of 1,020 participants from 12 randomized controlled trials were included. Botulinum toxin-A was associated with less urinary frequency, less incontinence episodes, improvement in quality of life, higher post-void residual-related catheterization and higher urinary tract infection. Doses of 100-300 U were not consistently differentiated from each other in voiding diary, quality of life and urge urinary incontinence. No statistically significant difference was seen between bladder body and bladder base, bladder body and bladder body plus trigone in urinary retention and urinary tract infection. Conclusion: Botulinum toxin-A is associated with significant improvement in OAB symptoms in patients with idiopathic OAB. However, there is a higher incidence of postoperative urinary retention and urinary infection compared to placebo. Low-dose botulinum toxin-A seems to be the optimum dose that appropriately balances the benefits with adverse events. Trigone inclusion seems as safe and effective as trigone-sparing injection.

Efficacy and Safety of OnabotulinumtoxinA for Idiopathic Overactive Bladder: A Double-Blind, Placebo Controlled, Randomized, Dose Ranging Trial

Treatment options for patients with overactive bladder refractory to anticholinergics are limited. We assessed the dose response across a range of doses of onabotulinumtoxinA (BOTOX®) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics. In a phase 2, multicenter, randomized, double-blind study, 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50, 100, 150, 200 or 300 U intradetrusor onabotulinumtoxinA, or placebo. Symptoms were recorded using a 7-day bladder diary. The primary efficacy variable was weekly urinary urgency incontinence episodes and the primary end point was week 12. Demographics and baseline characteristics were balanced across the treatment groups. Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater for primary and secondary efficacy measures, including the proportion of incontinence-free patients. When the dose response curves were analyzed, doses greater than 150 U contributed minimal additional or clinically relevant improvement in symptoms. This finding was also reflected in health related quality of life assessments. Dose dependent changes in post-void residual urine volume were observed and the use of clean intermittent catheterization was also dose dependent. The only adverse events significantly greater with onabotulinumtoxinA than with placebo were urinary tract infection and urinary retention. OnabotulinumtoxinA at doses of 100 U or greater demonstrated durable efficacy in the management of idiopathic overactive bladder and urinary urgency incontinence. A dose of 100 U may be the dose that appropriately balances the symptom benefits with the post-void residual urine volume related safety profile.

The second-line management of idiopathic overactive bladder: what is the place of sacral neuromodulation and botulinum toxin-A in contemporary practice?

The second-line management of idiopathic overactive bladder: what is the place of sacral neuromodulation and botulinum toxin-A in contemporary practice?