Beta-Agonist Versus OnabotulinumtoxinA Trial for Urgency Urinary Incontinence

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare treatment outcomes between an oral medication (beta agonist) versus onabotulinumtoxinA injections in women with urgency urinary incontinence (UUI). Participants will be randomly selected to receive one of the two treatments. The primary outcome measure will be at 3 months, and women will be followed for a total of 12 months. Based on patient expert input, there are 2 primary outcomes: Treatment satisfaction and urinary symptom severity.

Detailed Description
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The purpose of this study is to directly compare 2 primary outcomes (Treatment satisfaction and urinary symptom severity) between beta agonist oral medication versus onabotulinumtoxinA intradetrusor bladder injection for the treatment of UUI. The study will also compare secondary outcomes identified as important by patients. At the end of the study, the investigators will have patient and stakeholder-derived comparative outcomes between these 2 commonly available treatment categories. A stakeholder and community engagement (CE) plan will be developed and implemented. The investigators will also develop a model to help guide patients and providers through this decision process. SPECIFIC AIMS Specific Aim 1: Compare the efficacy of beta agonist versus onabotulinumtoxinA on patient-important treatment outcomes at 3 months in women with UUI. This multi-center, randomized clinical trial (RCT) includes 5 sites across the U.S. Two co-primary outcomes will be measured using validated patient-reported outcomes (PROs), selected by patients: Co-primary outcome 1: Symptom severity, measured by change in Overactive Bladder Questionnaire-Symptom Bother Scale (OAB-q-SS) score. Co-primary outcome 2: Treatment satisfaction, measured by the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General (FACIT-TS-G), powered based on a single item. Specific Aim 2: Compare secondary patient-important outcomes. Direct comparisons between intervention effects on secondary outcomes chosen by patients and stakeholders, including adverse events, UUI quality of life, global improvement, and sexual function. Specific Aim 3: Use predictive modeling to help stakeholders better determine expected outcomes after treatment with beta agonist versus onabotulinumtoxinA. Comparators: Beta agonist oral medication (mirabegron or vibegron) versus intradetrusor onabotulinumtoxinA. Both beta-agonists and onabotulinumtoxinA are US Food and Drug Administration (FDA) approved for the treatment of UUI, and widely available options with established efficacy. 432 women will be randomly assigned to each treatment option: 216 to beta agonist oral medication and 216 to intradetrusor onabotulintoxinA. Women will be undergo outcomes assessments at 3, 6, 9, and 12 months. The primary outcome measure will be at 3 months.

Official Title
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Beta-Agonist Versus OnabotulinumtoxinA Trial for Urgency Urinary Incontinence

Conditions
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Urgency Urinary Incontinence

Intervention / Treatment
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* Drug: Beta3-Agonists, Adrenergic [Mirabegron/Vibegron]
* Drug: OnabotulinumtoxinA 100 UNT [Botox]


Participation Criteria
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Eligibility Criteria
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Inclusion criteria*: 18 years or older report at least quite a bit bothered or worse by their UUI defined by response to OAB-q-SS item #8 How bothered are you by urine loss associated with a strong desire to urinate? are not and do not plan to become pregnant have persistent UUI defined as previous unsuccessful results after conservative and anticholinergic treatment, or are unable to tolerate or have contraindications to anticholinergics are currently not taking anticholinergics or are willing to stop medication for 3 weeks prior to enrollment. for participants reporting mixed urinary incontinence symptoms, participant must (a) have less bother from SUI than from UUI, defined as a response of Not at all bothered or only a little bit bothered by SUI on the Urogenital Distress Inventory item Do you experience urine leakage related to physical activity? (walking, running, laughing, sneezing, coughing), and (b) SUI symptoms be stable (> 3 months), and (c)participant does not desire additional treatment for SUI in the upcoming 3 months. Participants after unsuccessful neuromodulation trial can be eligible after a 4-week washout period. Exclusion criteria: clinical contraindication to beta-3 agonist or onabotulinumtoxinA prior therapeutic trial of either study treatment unevaluated hematuria, current or prior bladder malignancy surgically altered detrusor muscle prior pelvic radiation post-void residual >150 mL in past 3 months neurogenic bladder pelvic floor surgery within the past 3 months anticipating pelvic surgery within primary outcome follow up period (3 months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At 3 months, the effect of treatment with beta agonist oral medication or onabotulinumtoxinA will be evaluated within a classic RCT model. The analysis will determine the effect of treatment on the co-primary outcomes: Treatment satisfaction and urinary symptom severity.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Beta-3 receptor agonist oral medication<br>Selective beta-3 receptor agonist oral medication approved for the treatment of urgency urinary incontinence including mirabegron or vibegron. Usual clinical care standards will be used for prescribing and dosing changes. For mirabegron, dosages are 25 mg and 50 mg as clinically indicated. For vibegron, dosage is 75 mg daily by mouth as clinically indicated. | Drug: Beta3-Agonists, Adrenergic [Mirabegron/Vibegron]<br>* The beta-agonist oral medication will be prescribed and dose adjusted per usual care.<br>|
| Active Comparator: Intradetrusor onabotulinumtoxinA<br>OnabotulinumtoxinA at a dose of 100 units will be injected into the bladder per usual care pathways. | Drug: OnabotulinumtoxinA 100 UNT [Botox]<br>* OnabotulinumtoxinA will be prepared by dissolving 100 units into 10 ml of injectable saline. The injection will be an office based procedure, performed per usual care.<br>* Other names: Botox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in score Overactive Bladder Questionnaire-Symptom Bother Scale (OAB-q-SS) at 3 months | 8-item questionnaire measuring symptom bother of overactive bladder symptoms, higher scores indicate more bothersome symptoms | Baseline until 3 months | 
| Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General Questionnaire (FACIT-TS-G) at 3 months | Single item How do you rate this treatment overall on a 5-point likert scale | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Overactive Bladder Questionnaire-Symptom Bother Scale (OAB-q-SS) | 8-item questionnaire measuring symptom bother of overactive bladder symptoms | Baseline until 6, 9, 12 months | 
| Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General Questionnaire (FACIT-TS-G) at 3 months | 8-item questionnaire assessing treatment satisfaction of adults undergoing treatment for chronic conditions | 6, 9, 12 months | 
| Change in Overactive Bladder Questionnaire-Health Related Quality of Life (OAB-q-HRQL) | Overactive bladder disease specific questionnaire measuring quality of life, higher scores indicate better HRQL | Baseline to 3, 6, 9, 12 months | 
| Change in Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-IR) | Validated tool assessing female sexual function in women with pelvic floor disorders; higher scores reflect better sexual functioning | Baseline to 3, 6, 9, 12 months | 
| Patient global impression of improvement (PGI-I) | Global measure of patient impression of improvement, likert scale | 3, 6, 9, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UUI, Urgency Incontinence, Beta Agonist, onabotulintoxinA, Botox, Community Engagement