Role of Combination Therapy in Women With Refractory Overactive Bladder
- Conditions
- Overactive Bladder Syndrome
- Interventions
- Drug: Placebo
- Registration Number
- NCT06438861
- Lead Sponsor
- University of Alabama at Birmingham
- Brief Summary
Defined by the International Continence Society (ICS) as urinary "urgency, with or without urge incontinence, usually with frequency and nocturia", overactive bladder (OAB) presents as challenging syndrome to treat. OAB is a very prevalent condition, affecting between 11.8% to 16% of the population with equal impact on women and men and growing prevalence with age. OAB is associated with a significant financial burden to both patients and the health care system with a estimated cost of US $82.6 billion in 2020. Traditionally, a stepwise approach has been taken in managing OAB; starting first with lifestyle modifications, followed by anticholinergic or beta-3-agonist medications as the second line, and lastly, intradetrusor onabotulinumtoxinA injections, percutaneous tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM) as third line options. Given the limitations of this stepwise approach in patients with refractory OAB, combination therapy offers patients an increasing number of treatment options but the literature surrounding the efficacy of combination therapy is somewhat limited. A 2019 systematic review revealed there were only 32 studies in the current OAB literature that explored the role of combination therapy, and the majority of these studies examined the effect of lifestyle modifications with another intervention strategy, highlighting an untapped area of research5.
To date, there has only been a single pilot study conducted in Taiwan examining the effect of intradetrusor onabotulinumtoxinA injections with the addition of mirabegron for patients with refractory OAB. This study by Wang et al. explored the therapeutic impact of adding either an anticholinergic, solifenacin, or a beta-3 agonist, mirabegron, to intradetrusor onabotulinumtoxinA injections as compared to each other as well as patients receiving onabotulinumtoxinA alone. Ninety patients were enrolled with 30 patients allocated to the solifenacin arm, 31 to the mirabegron arm, and 29 to the control group. While the baseline data among the three arms was comparable, the percentage of OAB wet in the mirabegron plus onabotulinumtoxinA group was significantly less at 3-, 6-, 9-, and 12-month intervals than the solifenacin plus onabotulinumtoxinA and the onabotulinumtoxinA alone groups. While this pilot study reveals the potential additive benefit of a beta-3 agonist to intradetrusor onabotulinumtoxinA, no further studies have been performed to date and there are no studies regarding the additive benefit of vibegron, which has a more tolerable side effect profile and is not as limited by as many contraindications as mirabegron. If vibegron can potentiate the effect of intradetrusor onabotulinumtoxinA, this presents a new treatment strategy for OAB and could offer patients an additional line of therapy before having to pursue more invasive and costly management option of sacral neuro modulation.
- Detailed Description
The study will be a prospective double-blinded randomized control trial to examine the effect of administering vibegron versus placebo in conjunction with intradetrusor onabotulinumtoxinA injections for the management of refractory OAB. Patients who present to the University of Alabama at Birmingham urogynecology practice with refractory OAB undergoing the standard 100U intradetrusor onabotulinumtoxinA will be offered enrollment to either the onabotulinumtoxinA plus vibegron or the onabotulinumtoxinA plus placebo groups. Prior to onabotulinumtoxinA injections, patients' baseline demographics will be documented and their genitourinary symptoms will be assessed using the previously validated Urinary Distress Inventory Short Form (UDI-6), the Incontinence Impact Questionnaire Short Form (IIQ-7), the Overactive Bladder Questionnaire (The OAB-q), and a 3 day voiding diary. Patients will be blinded to which cohort they are randomized to. Each patient will undergo intradetrusor onabotulinumtoxinA injections of 100U either in the office or in the operating room depending on patient and provider preference. Patients will begin taking vibegron or a placebo pill daily starting the day of their procedure. At 12 weeks, patients will complete a 3 day voiding diary as well as the UDI-6, IIQ-7, and OAB-q questionnaires. Patient charts will be queried for timing of repeat onabotulinumtoxinA injection as another secondary outcome.
Primary outcome: Change in mean urinary urgency incontinence episodes at 12 weeks based on 3 day voiding diary
Secondary outcomes: Mean change in UDI-6 responses at 12 weeks, mean change in IIQ-7 responses at 12 weeks, mean change in OAB-q responses at 12 weeks, duration to repeat onabotulinumtoxinA injection
Sample Size Calculation:
It is anticipated that women randomized to the 100U intradetrusor onabotulinumtoxinA plus vibegron arm will experience a greater improvement in UUI episodes compared to the 100U intradetrusor onabotulinumtoxinA plus placebo cohort. A recent study comparing the PTNS plus mirabegron to PTNS plus placebo performed a sample size calculation using existing data 7,8. In that calculation, a 2-sided alpha=0.05, the estimate for that difference in improvement had been estimated to be 2.5 UUI episodes over a 3-day bladder diary pre-vs. post-treatment with a standard deviation of 3 and a power of 0.80 and given the assumed attrition rate of 10%, the total N per arm was estimated to be 27 subjects for the study. Given the similarities between this study and our proposed study, the sample size calculation was felt be applicable to this study.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 54
- Women undergoing intradetrusor botulinum injections for refractory OAB
- Age 18 years old or greater
- Fluency and literacy in English
- Capacity to provide consent
- Allergy to Vibegron
- Currently pregnant or planning to become pregnant
- Breastfeeding
- Current digoxin use
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 100U intradetrusor onabotulinumtoxinA plus placebo Placebo Each patient will undergo intradetrusor onabotulinumtoxinA injections of 100U either in the office or in the operating room depending on patient and provider preference. Patients randomized to this arm will begin taking a placebo pill daily starting the day of their procedure and continue for 3 months. 100U intradetrusor onabotulinumtoxinA plus vibegron Vibegron 75mg Each patient will undergo intradetrusor onabotulinumtoxinA injections of 100U either in the office or in the operating room depending on patient and provider preference. Patients randomized to this arm will begin taking vibegron 75mg daily, which is the standard dose, starting the day of their procedure and continue for 3 months.
- Primary Outcome Measures
Name Time Method Change in urinary urgency incontinence (UUI) episodes on 3 day voiding diary at 12 weeks after starting treatment as compared to baseline Pre-intervention baseline to 12 weeks following initiation of intervention Patients will be asked to complete a 3 day voiding diary at baseline and at 12 weeks following intradetrusor onabotulinumtoxinA injections and oral medication. The mean change in UUI episodes will be compared between the onabotulinumtoxinA injection plus vibegron verus onabotulinumtoxinA injection plus placebo groups.
- Secondary Outcome Measures
Name Time Method Change in UUI (Urge Urinary Incontinence)/OAB (Overactive Bladder) Quality of Life as Measured by the Incontinence Impact Questionnaire Short Form (IIQ-7) Questionnaire Pre-Intervention versus 12 weeks Post-Intervention Pre-intervention baseline to 12 weeks following initiation of intervention The IIQ-7 is the short form validated patient questionnaire that was developed from the incontinence impact questionnaire (IIQ). It consists of seven questions that focus on the impact of UUI on physical activity, travel, relationships, and emotional health. The responses are scored as follows: (0) not at all, (1) slightly, (2) moderately, (3) greatly. The mean score is multiplied by 33 1/3 to convert to a 0 to 100 scale with higher scores indicative of more symptoms distress. Subjects will complete the IIQ-7 survey at baseline and at 12 weeks post-intervention. The mean change in IIQ-7 responses will be compared.
Change in Symptom Distress as Measured by the Urogenital Distress Index (UDI-6) Questionnaire Pre-Intervention versus 12 weeks Post-Intervention Pre-intervention baseline to 12 weeks following initiation of intervention The UDI-6 is the short form validated patient questionnaire that was developed from the urogenital distress inventory (UDI). It consists of six questions that focus on lower urinary tract dysfunction including obstructive, irritative, and stress symptoms. The responses are scored as follows: (0) not at all, (1) slightly, (2) moderately, (3) greatly. The mean score is multiplied by 33 1/3 to convert to a 0 to 100 scale with higher scores indicative of more symptoms distress. Subjects will complete the UDI-6 survey at baseline and at 12 weeks post-intervention. The mean change in UDI-6 responses will be compared.
hange in UUI (Urge Urinary Incontinence)/OAB (Overactive Bladder) Quality of Life as Measured by the Overactive Bladder Questionnaire-Short Form (OAB-q SF) Questionnaire Pre-Intervention versus 12 weeks Post-Intervention Pre-intervention baseline to 12 weeks following initiation of intervention The OAB-q SF is the short form validated patient questionnaire that was developed from the Overactive Bladder Questionnaire (OAB-q). It consists of six questions that focus on the impact of bladder symptoms over the past 4 weeks. The responses are scored as follows: (1) not at all, (2) a little bit, (3) somewhat, (4) quite a bit, (5) a great deal, (6) a very great deal. The mean score is converted to a 0 to 100 scale with higher scores indicative of more symptoms distress. Subjects will complete the OAB-q SF survey at baseline and at 12 weeks post-intervention. The mean change in OAB-q SF responses will be compared.
Duration to repeat onabotulinumtoxinA injection Initiation of intervention until repeat injection, anticipate average of 1 year Patient require repeat intradetrusor onabotulinumtoxinA injection to treat refractory OAB. A chart review will be performed to determine time interval between initial onabotulinumtoxinA injection and subsequent injection to see if there is a difference with the addition of vibegron as compared to placebo.