Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder.

AIMS: In studies utilizing a 20-injection-site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10-injection-site paradigm targeting the lower bladder. METHODS: In this phase 4, double-blind, parallel-group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI-free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder. RESULTS: Of 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double-blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (-2.9) versus placebo (-0.3) (least squares mean difference [LSMD]: -2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75-50.37]), ≥75% (OR: 7.25 [2.00-26.29]), and ≥50% improvement (OR: 4.79 [1.87-12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: -2.24, p < 0.0001), nocturia (LSMD: -0.71, p = 0.0004), and urgency (LSMD: -2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23-52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double-blind period; no females used CIC during the double-blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo. CONCLUSION: In patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.

Taking OAB seriously: A qualitative evaluation of primary care education on overactive bladder syndrome management.

BACKGROUND: Overactive bladder (OAB) syndrome has a diverse etiology that disrupts quality of life domains in affected patients. OAB is significantly under-recognised and undertreated, especially in the primary care setting. In order to educate primary care providers about OAB recognition, evaluation and management, we created a virtual live-streamed and enduring education program. METHODS: We evaluated the impact of education on provider knowledge and self-efficacy via qualitative interviews with a sample of education participants. We analysed participant responses via constant comparative method, an iterative approach that allows for exploration of a priori issues and identification of emergent themes. RESULTS: We identified four key themes: (a) taking OAB seriously; (b) variations in therapy; (c) patient motivation; and (d) education value. Participants were proactive about screening for and managing OAB and recognised urgency as a key symptom; some participants used diagnostic tests that are not are not considered necessary in the workup of uncomplicated OAB patients. Participants varied in their descriptions of initial approaches to treatment and most participants described a longer-than-recommended follow-up window to monitor patients. Some participants characterised patients as looking for a "quick fix" in ways that could lead to provider inaction in relation to behavioural/lifestyle interventions. Overall, participants felt that the education validated their current practice and provided new knowledge about evaluation, initiating behavioural treatment, and combination therapy. CONCLUSIONS: Participant responses were congruent with education messages, which likely reflect their "readiness to learn". The rationale for diagnostic tests and evidence on the effectiveness of behavioural regimens represent ongoing areas of unmet educational need.

Feasibility of a Fully Implanted, Nickel Sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence.

PURPOSE: We performed a clinical feasibility trial to evaluate the safety and efficacy of a fully implanted, primary battery powered, nickel sized and shaped neuromodulation device called the eCoin® for tibial nerve stimulation to treat refractory urgency urinary incontinence. MATERIALS AND METHODS: This prospective, single arm, open label study included 46 participants with refractory urgency urinary incontinence. It was performed at multiple sites in the United States and New Zealand. The device was implanted in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality of life instruments were collected 3 and 6 months after activation and compared to baseline values. RESULTS: The mean ± SD age of participants was 63.4 ± 11.5 years and 45 (98%) were female. Episodes of urgency urinary incontinence were reduced a relative median of 71% after 3 months of treatment (4.2 vs 1.7 daily episodes at 3 months, p = 0.001). A 50% or greater decrease in reported episodes of urgency urinary incontinence was observed in 32 of 46 participants (69.6%) at 3 months with more than 20% dry at 3 and 6 months. I-QOL (Incontinence Quality of Life) scores improved an average of 25.9 points and 33 of 46 patients (72%) indicated improvement in symptoms. A single serious adverse event secondary to wound care resolved with intravenous antibiotics. CONCLUSIONS: The implantable neuromodulation device was a safe and effective treatment of urgency urinary incontinence associated with overactive bladder syndrome with a significant reduction or resolution of symptoms and no significant safety concerns.

Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials.

PURPOSE: SER120 desmopressin intranasal spray is the first U.S. Food and Drug Administration approved pharmacotherapy for nocturia. We evaluated its efficacy and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and DB4. MATERIALS AND METHODS: A total of 1,333 intent to treat patients 50 years old or older with 2.16 or more nocturic voids per night during a 2-week screening period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or placebo for a 12-week treatment. Co-primary end points were the mean change from baseline in nocturic episodes per night and the percent of patients with a 50% or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) quality of life questionnaire in DB4, time to the first nocturic void and the percent of nights with 1 or fewer nocturic voids. RESULTS: Each SER120 dose showed statistical significance vs placebo for the 2 co-primary end points, including the mean nocturic episodes per night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p <0.0001), the percent of patients with a 50% or greater reduction in mean nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3% with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary end points in the pooled analyses. The 1.66 mcg dose demonstrated significant improvements in the INTU score (p = 0.0255). The incidence of hyponatremia, defined as serum sodium 125 mmol/l or less regardless of symptoms or less than 130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and placebo groups, respectively. Other adverse events were similar across treatment groups. CONCLUSIONS: SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.

A pilot feasibility study of treating overactive bladder patients with percutaneous saphenous nerve stimulation.

AIMS: Effective long-term treatment of overactive bladder (OAB) remains a significant clinical challenge. We present our initial experience with a new bladder neuromodulation method that electrically targets the saphenous nerve (SAFN). METHODS: A total of 18 OAB patients (female, 55-84 years) were provided with percutaneous SAFN stimulation. The SAFN was targeted with a needle electrode inserted below the medial condyle of the tibia. Activation of the SAFN was confirmed by the patient's perception of paresthesia radiating down the leg. Electrical stimulation was applied for 30 min and subsequently repeated weekly for 3 months. The effects of stimulation were assessed by a 4-day bladder diary and quality-of-life questionaire (OAB-q). RESULTS: Percutaneous SAFN stimulation was confirmed in all 16 patients who completed the study, and no adverse events were reported. Positive response to SAFN stimulation was achieved in 87.5% (14 of 16) of patients, as determined by either a minimum 50% reduction in bladder symptoms or a minimum 10 point increase in the HRQL total score. CONCLUSIONS: Electrical activation of the SAFN was consistently achieved using anatomical landmarks and patient feedback. The procedure was well tolerated and, based on our small cohort of patients, appears efficacious, and safe. This pilot study provides early feasibility data that points to a promising new intervention for treating OAB.

Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add-on mirabegron therapy to solifenacin (BESIDE).

AIMS/OBJECTIVES: In the BESIDE study, combination therapy (antimuscarinic [solifenacin] and ß3 -adrenoceptor agonist [mirabegron]) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. METHODS: OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters. RESULTS: The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy; SBP was unchanged with combination and decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77 mseconds). CONCLUSION: The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined.

Mirabegron as Add-On Treatment to Solifenacin in Patients with Incontinent Overactive Bladder and an Inadequate Response to Solifenacin Monotherapy: Responder Analyses and Patient-Reported Outcomes from the BESIDE Study [corrected].

PURPOSE: We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg. MATERIALS AND METHODS: Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC. RESULTS: Overall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 and 10 mg (OR 1.47, 95% CI 1.17-1.84, p = 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively). CONCLUSIONS: Significantly more patients on the combination achieved clinically meaningful improvements in incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.

Validation of a bladder symptom screening tool in women with incontinence due to overactive bladder.

INTRODUCTION AND HYPOTHESIS: The Actionable Bladder Symptom Screening Tool (ABSST) was initially developed to identify patients with multiple sclerosis (MS) who could benefit from lower urinary tract assessment and treatment. Assessment of the measurement properties of the ABSST, including its ability to identify patients experiencing bladder symptoms related to overactive bladder (OAB), was undertaken in a general female population. METHODS: One hundred women completed the ABSST, OAB Questionnaire Short Form (OAB-q SF), and a patient global impression of severity (PGI-S) scale. Half of the sample had urgency urinary incontinence (UUI), while the other half did not. Descriptive statistics, reliability, and validity were examined, as was sensitivity and specificity of the previous cut-off score established in MS. RESULTS: Fifty-three women with UUI/OAB and 47 controls took part (71.0 % Caucasian). Patients with UUI/OAB were older (54.6 vs 40.4 years), had a higher body mass index (31.1 vs 26.4 kg/m(2)), and more comorbid conditions. The Cronbach's alpha reliability of ABSST was 0.90. High correlations with OAB-q SF Symptom Bother and Health Related Quality of Life (r = 0.83 and -0.81 respectively) supported concurrent validity. Using the PGI-S severity scores as a reference, the ABSST was able to distinguish patients with differing severity levels (known-group validity). Physician assessment of the need for further evaluation/treatment showed sensitivity (79 %) and specificity (98 %), supporting a cut-off score of ≥3. CONCLUSIONS: The previous MS ABSST scoring algorithm was validated in a non-neurogenic female population. ABSST is a reliable, valid, and sensitive tool for screening women with UUI/OAB.

Two-year Pivotal Study Analysis of the Safety and Efficacy of Implantable Tibial Nerve Stimulation With eCoin for Urgency Urinary Incontinence.

OBJECTIVE: To evaluate the continued effectiveness and safety of the eCoin Implantable Tibial Nerve Stimulator system (ITNS) for urgency urinary incontinence (UUI) in patients with overactive bladder (OAB). The 1-year pivotal study was extended through 2 years. The ITNS is a novel and recently FDA-approved therapy. METHODS: A prospective, multicenter, single-arm trial was conducted on 137 subjects with refractory UUI to evaluate eCoin ITNS therapy. A 3-day voiding diary was collected along with the OAB questionnaire, Patient Global Impression of Improvement, and a custom Likert scale on subject satisfaction. The primary efficacy measure was the proportion of subjects who achieved at least 50% reduction from baseline in number of UUI episodes. The primary safety measure was device-related adverse events (AEs). RESULTS: Seventy-two subjects completed the 96-week evaluation. Around 78% (95% CI: 67%-87%) experienced at least 50% reduction in UUI episodes; 48% (95% CI, 36%-60%) experienced at least 75% reduction, and 22% (95% CI, 13%-33%) were dry on a 3-day diary. Subjects reported a decrease from baseline in their UUI episodes/day of 2.61 (SD 2.97) and 2.97 (SD 2.64) at 48 weeks and 96 weeks, respectively. Around 91.3% did not require additional medications for OAB. No serious or unanticipated AEs were reported in this extension phase. CONCLUSION: The eCoin ITNS demonstrated consistent continuing effectiveness and safety in treating OAB patients with UUI. The findings support it as an excellent treatment option for refractory patients.

Tibial Nerve Stimulation for Urge Urinary Incontinence and Overactive Bladder: Narrative Review of Randomized Controlled Trials and Applicability to Implantable Devices.

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve.

Cost of neuromodulation therapies for overactive bladder: percutaneous tibial nerve stimulation versus sacral nerve stimulation.

PURPOSE: Conservative therapy and antimuscarinic agents are first line therapies for overactive bladder. Patients refractory to treatment are candidates for neuromodulation therapy. We estimated the costs and cost-effectiveness of percutaneous tibial nerve stimulation and sacral nerve stimulation. MATERIALS AND METHODS: A Markov model was constructed to simulate the total costs and effectiveness of percutaneous tibial and sacral nerve stimulation during 2 years. Cost data used average Medicare national physician payments, and ambulatory payment classification and diagnosis related group payments for hospital based care and office visits. Clinical effectiveness, and the rates of patient adherence to treatment and adverse events were estimated by a review of the literature. RESULTS: The costs of initial therapy were $1,773 for 12 weekly percutaneous tibial nerve stimulation treatments and $1,857 for test sacral nerve stimulation. For ongoing therapy the cost of the sacral nerve stimulation surgical implant was $22,970. Cumulative discounted 2-year costs were $3,850 for percutaneous tibial nerve stimulation and $14,160 for sacral nerve stimulation, including those who discontinued therapy. Of the patients 48% and 49%, respectively, remained on therapy. The incremental cost-effectiveness ratio was $573,000 per additional patient on sacral nerve stimulation. When considering only patients who completed initial stimulation successfully, the costs were $4,867 and $24,342 for percutaneous tibial and sacral nerve stimulation with 71% and 90%, respectively, remaining on therapy for an incremental cost-effectiveness ratio of $99,872. CONCLUSIONS: Percutaneous tibial nerve stimulation and sacral nerve stimulation are safe, effective neuromodulation therapies for overactive bladder. In this economic model percutaneous tibial nerve stimulation had substantially lower cost. An additional 1% of patients would remain on therapy at 2 years if sacral nerve stimulation were used rather than percutaneous tibial nerve stimulation but the average cost per additional patient would be more than $500,000.

Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study.

PURPOSE: We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent® PC Neuromodulation System for overactive bladder after 3 years of therapy. MATERIALS AND METHODS: Fifty participants in the randomized, double-blind SUmiT (Sham Effectiveness in Treatment of Overactive Bladder Symptoms) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospective study to assess long-term outcomes with percutaneous tibial nerve stimulation. STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aimed at sustaining overactive bladder symptom improvement. Overactive bladder and quality of life questionnaires were completed every 3 months and 3-day voiding diaries were completed every 6 months. RESULTS: A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol. A Bayesian model estimated that 77% (95% CI 64-90) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years. Compared to baseline, median voids per day decreased from 12.0 (IQR 10.3-13.7) to 8.7 (IQR 7.3-11.3), nighttime voids per night decreased from 2.7 (IQR 1.7-3.3) to 1.7 (IQR 1.0-2.7) and urge incontinence episodes per day decreased from 3.3 (IQR 0.7-6.0) to 0.3 (IQR 0.0-1.0) (all p <0.0001). All quality of life parameters remained markedly improved from baseline through 3 years (all p <0.0001). One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup. CONCLUSIONS: Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month.

Development of a short form and scoring algorithm from the validated actionable bladder symptom screening tool.

BACKGROUND: The majority of multiple sclerosis (MS) patients develop some form of lower urinary tract dysfunction, usually as a result of neurogenic detrusor overactivity (NDO). Patients identify urinary incontinence as one of the worst aspects of this disease. Despite the high prevalence of NDO, urological evaluation and treatment are significantly under-accessed in this population. The objectives of this study were: 1) to adapt the previously validated Actionable Bladder Symptom Screening Tool (ABSST) to a short form for ease and brevity of application in a clinical setting that is clinically meaningful; and 2) to develop a scoring algorithm that would be interpretable in terms of referring/considering precise diagnosis and treatment. METHODS: A US-based, non-randomized, multi-center, stand-alone observational study was conducted to assess the psychometric properties of the ABSST among patients who have MS with and without NDO. Mixed psychometric methods (e.g., classical statistics (Psychometric theory (3rd ed.). New York: McGraw-Hill; 1994) and item response methods (Applying the Rasch Model: Fundamental Measurement in the Human Sciences. New Jersey: Lawrence Earlbaum Associates; 2001)) were used to evaluate the predictive and clinical validity of the shortened form. The latter included clinicians flagging clinically meaningful items and associated response options which would indicate the need for further evaluation or treatment. RESULTS: A total of 151 patients, all with MS and with and without NDO, were recruited by 28 clinicians in various US geographical locations. Approximately 41% of patients reported a history of or currently having urinary incontinence and/or urinary urgency. The prediction model across the entire range of classification thresholds was evaluated, plotting the true positive identification rate against the false positive rate (1-Specificity) for various cut scores. In this study, the cut-point or total score of greater than or equal to 6 had a sensitivity of approximately 85%, and specificity of approximately 93% (i.e., 85% patients would warrant being referred to a urologist and 93% of the patients whose symptoms would not warrant urologist referral). CONCLUSIONS: Overall the short form ABSST demonstrated sensitivity and specificity as it maintained the integrity of the longer form tool. Concurrent validity for each subscale as well as predictive and concurrent validity of the total shortened instrument was demonstrated. This instrument provides a new method for assessing bladder problems among MS patients, and may facilitate earlier and more precise diagnosis, treatment, and/or referral to a specialist.

Sustained therapeutic effects of percutaneous tibial nerve stimulation: 24-month results of the STEP study.

AIMS: To evaluate the safety, sustained effectiveness, and treatment interval for percutaneous tibial nerve stimulation (PTNS) for overactive bladder (OAB) therapy through 24 months. METHODS: A prospective study following treatment success after 12 weekly PTNS treatments, subjects were prescribed a 14-week tapering protocol, followed by ongoing therapy with a Personal Treatment Plan determined by the investigator and subject to sustain subject OAB symptom improvement. Questionnaires were completed every 3 months, voiding diaries every 6 months; adverse events were reported throughout. RESULTS: Of 50 subjects enrolled, 35 remained in the study at 24 months. During the 24 months following initial treatment success and a 14-week tapering protocol, mean treatments per month was 1.3. Voiding diary and OAB-q data demonstrate sustained improvement reported at 13 weeks through 24 months. Improvements in frequency, urge incontinence episodes, night-time voids and moderate-to-severe urgency episodes from voiding diaries at 6, 12, 18, and 24 months were statistically significant compared to baseline (prior to initial 12 weekly treatments). Compared to baseline, OAB-q symptom severity scores and health related quality of life scores were statistically significant for improvement at each tested time point. Five mild adverse events of unknown relation to treatment were reported. CONCLUSION: Sustained safety and efficacy of PTNS were demonstrated over 24 months with initial success after 12 weekly treatments, followed by a 14-week prescribed tapering protocol and a Personalized Treatment Plan. With an average of 1.3 treatments per month, PTNS therapy is a safe, durable, and valuable long-term OAB treatment option to sustain clinically significant OAB symptom control.

Percutaneous tibial nerve stimulation: a clinically and cost effective addition to the overactive bladder algorithm of care.

Overactive bladder affects millions of adults, with profound personal and economic costs. Although antimuscarinic drugs can cause a reduction in voiding symptoms, the effect is modest, and many patients are intolerant of the side effects, or do not experience sufficient relief. For these patients, the modulation of bladder reflex pathways via percutaneous tibial nerve stimulation (PTNS) or via implanted sacral nerve stimulation (SNS) has been acknowledged as a logical next step in the algorithm of care. This review examines the mechanism of action, the relative benefits, adverse effects, and costs of percutaneous nerve stimulation compared to other treatment modalities.

Six-Month Outcomes of Reimplantation of a Coin-Sized Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome With Urgency Urinary Incontinence.

OBJECTIVE: The eCoin (Valencia Technologies Corporation, Valencia, CA) is a battery-powered, nickel-sized and shaped neuromodulation device for the treatment of overactive bladder, and it is implanted in the lower leg in a short office or outpatient procedure under local anesthesia. A follow-on trial was conducted to evaluate the feasibility, safety, and efficacy of eCoin reimplantation. METHODS: This was a prospective, single-arm, open-label study, including 23 participants with refractory urgency urinary incontinence (UUI) who were previously participants in the eCoin clinical feasibility trial. This follow-on study was conducted at 7 sites in the United States and New Zealand. Participants were reimplanted with a new eCoin device and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 12 weeks and 24 weeks postactivation, were compared with baseline. RESULTS: Participants of the study were considered responders if they reported a ≥ 50% reduction from baseline in episodes of UUI on a 3-day voiding diary. At 12 weeks of treatment, 74% (95% confidence interval [CI], 52%-90%) of participants were considered responders. At 24 weeks of treatment, 82% (95% CI, 60%-95%) of participants were considered responders with 36% (95% CI, 20%-57%) of participants achieving complete continence. There were no device-related serious adverse events reported during the study. CONCLUSIONS: The reimplantation of eCoin was both safe and effective in treating UUI associated with overactive bladder syndrome. The demonstrated significant reduction or resolution of symptoms with no serious safety concern suggests that eCoin is a convenient and maintainable therapeutic device.

Twelve-month Durability of a Fully-implanted, Nickel-sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence: A Single-Arm, Prospective Study.

OBJECTIVES: To evaluate the safety and efficacy of the eCoin - a nickel-sized, primary battery-powered, neuromodulation device for the treatment of urgency urinary incontinence which is implanted in the lower leg in a 20-minute procedure under local anesthesia. A feasibility clinical trial was conducted and the results after 1 year of treatment with the eCoin are presented. METHODS: A total of 46 participants with refractory urgency urinary incontinence were included in this prospective, single-arm, open-label study. This study was conducted at 7 sites in the United States and New Zealand. Participants in this study were implanted with the eCoin in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 3, 6, and 12 months' post-activation, were compared to baseline values. RESULTS: Responders were defined as those who had a ≥50% reduction in reported episodes of urgency urinary incontinence. At 12 months', 65% of participants were considered responders with 26% of participants achieving complete continence. The median number of urgency urinary incontinence episodes per day decreased from 4.2 at baseline to 1.7 at 12 months'. Seventy percent of participants reported feeling "better", "much better", or "very much better" on the Likert 7-point maximum scale. One participant experienced a related serious adverse event. CONCLUSION: The eCoin is a safe and effective treatment for urgency urinary incontinence associated with overactive bladder syndrome, with significant reduction or complete resolution of symptoms and no significant safety concerns.

Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial.

PURPOSE: The Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) was a multicenter, double-blind, randomized, controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy. The improvement in global response assessment, voiding diary parameters, and overactive bladder and quality of life questionnaires was evaluated. MATERIALS AND METHODS: A total of 220 adults with overactive bladder symptoms were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy. Overactive bladder and quality of life questionnaires as well as 3-day voiding diaries were completed at baseline and at 13 weeks. Subject global response assessments were completed at week 13. RESULTS: The 13-week subject global response assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5% reporting moderately or markedly improved responses compared to 20.9% of sham subjects from baseline (p <0.001). All individual global response assessment subset symptom components demonstrated statistically significant improvement from baseline to 13 weeks for percutaneous tibial nerve stimulation compared to sham. Voiding diary parameters after 12 weeks of therapy showed percutaneous tibial nerve stimulation subjects had statistically significant improvements in frequency, nighttime voids, voids with moderate to severe urgency and urinary urge incontinence episodes compared to sham. No serious device related adverse events or malfunctions were reported. CONCLUSIONS: This pivotal multicenter, double-blind, randomized, sham controlled trial provides level I evidence that percutaneous tibial nerve stimulation therapy is safe and effective in treating overactive bladder symptoms. The compelling efficacy of percutaneous tibial nerve stimulation demonstrated in this trial is consistent with other recently published reports and supports the use of peripheral neuromodulation therapy for overactive bladder.

Long-term durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder.

PURPOSE: The Overactive Bladder Innovative Therapy Trial during phase 1 was a randomized trial demonstrating comparable effectiveness of percutaneous tibial nerve stimulation and extended-release tolterodine during 12 weeks of therapy for frequency, nocturia, urgency, voided volume and urge incontinence episodes. In this second phase of the Overactive Bladder Innovative Therapy Trial we assessed the sustained therapeutic efficacy of percutaneous tibial nerve stimulation in subjects with overactive bladder during 1 year. MATERIALS AND METHODS: After 12 weeks subjects randomized to weekly percutaneous tibial nerve stimulation with Urgent((R)) PC were offered an additional 9 months of treatment with assessments at 6 and 12 months from baseline. Outcome measures included voiding diary data, overactive bladder questionnaires, global response assessments and safety assessments. RESULTS: A total of 33 percutaneous tibial nerve stimulation responders continued therapy with 32 and 25 subjects completing 6 and 12 months of therapy, respectively. Subjects received a mean of 12.1 treatments during an average of 263 days, with a mean of 21 days (median 17) between treatments. Subject global response assessments showed sustained improvement from 12 weeks at 6 and 12 months, with 94% and 96% of responders, respectively. At 12 months mean improvements from baseline included a frequency of 2.8 voids daily (p <0.001), urge incontinence of 1.6 episodes daily (p <0.001), nocturia with 0.8 voids (p <0.05) and a voided volume of 39 cc (p <0.05). Overactive bladder questionnaire symptom severity was significantly improved from 12 weeks to 12 months (p <0.01) as well as from 6 to 12 months (p <0.01). No serious adverse events occurred. CONCLUSIONS: Statistically significant overactive bladder symptom improvement achieved with 12 weekly percutaneous tibial nerve stimulation treatments demonstrates excellent durability through 12 months. The durability of response demonstrates the effectiveness of percutaneous tibial nerve stimulation as a viable, long-term therapy for overactive bladder.

The pharmacokinetic profile of fesoterodine 8 mg with daytime or nighttime dosing.

PURPOSE: Diurnal variation can affect drug pharmacokinetics. Fesoterodine is a new antimuscarinic drug for the treatment of overactive bladder (OAB). We estimated the relative bioavailability of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine, following nighttime and daytime administration. METHODS: In this randomized, open-label, two-period, two-treatment crossover, single-dose study, healthy subjects received daytime and nighttime oral dosing of fesoterodine 8-mg sustained-release tablets, separated by a minimum 60-h washout period. Blood samples for 5-HMT PK determination were collected before dosing and at specified intervals up to 48 h postdose. Safety was assessed by adverse event (AE) reports. RESULTS: Fourteen subjects completed the study. Plasma concentration versus time profiles (AUC) of 5-HMT were similar for daytime and nighttime dosing. Mean AUC(infinity) 5-HMT values were 47.9 and 51.4 ng h/mL for nighttime and daytime dosing, respectively; the mean time to reach maximum concentration (C(max)) values were 3.9 and 5.0 ng/mL, respectively. Nighttime versus daytime AUC(infinity) and C(max) ratios of 5-HMT were 93 and 79%, respectively; 90% confidence intervals (CIs) indicated equivalence for AUC(infinity) but not for C(max). The median time to reach maximum concentration (T(max)) was 5.0 h for both dosing regimens, and the mean terminal elimination half-life (T((1/2))) was 5.9 and 5.7 h for nighttime and daytime dosing, respectively. Seven treatment-related AEs, most commonly headache, occurred in five subjects. CONCLUSIONS: The AUC values for daytime and nighttime administration of fesoterodine were equivalent. The 21% reduction in the C(max) for nighttime dosing is unlikely to be clinically relevant. No safety issues were apparent. These results support both daytime and nighttime administration of fesoterodine for OAB treatment.