Sling vs Botox for Mixed Incontinence

Study Overview
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Brief Summary
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The primary aim is to compare the effectiveness of intradetrusor injection of 100 unit injection of Botulinum toxin A to mid-urethral sling for change in MUI symptoms 6 months following treatment.

Detailed Description
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Mixed urinary incontinence (MUI), defined as the presence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI), is a challenging condition for which clinicians frequently use multiple sequential treatments that have undergone limited evaluation in rigorous clinical trials. The Mixed Urinary Incontinence: Mid-urethral Sling vs. Botox A (MUSA) trial will estimate the effect of Botulinum toxin A (Botox A ®) compared to mid-urethral sling for the treatment of MUI symptoms in 146 women. MUSA is a randomized 2-arm clinical trial. The purpose of MUSA is to: compare treatment with either Botulinum toxin A (Botox A ®) or mid-urethral sling for women with MUI characterize patient characteristics associated with treatment response The primary objective is to estimate the effect of intradetrusor injections Botulinum toxin A (Botox A ®) compared to mid-urethral sling for treatment of MUI in 146 women 6 months after treatment. The change in severity of MUI symptoms will be measured using the Urogenital Distress Inventory. Secondary objectives include identifying predictors of treatment failure and cost-effectiveness of treatments in this MUI population. The study will continue with an additional 6 month observational period until 12 months post treatment. A supplemental study will characterize baseline putative proteins/protein pathways in women with MUI associated with change in UDI after treatment with MUS or onabotulinum toxin A.

Official Title
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Treatment for Mixed Urinary Incontinence: Mid-urethral Sling vs. Botox A

Conditions
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Urinary Incontinence, Stress, Urinary Incontinence, Urge

Intervention / Treatment
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* Drug: Botox® injection
* Device: Mid-urethral sling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Reporting at least moderate bother from UUI item on UDI * Do you experience urine leakage associated with a feeling of urgency? Reporting at least moderate bother from SUI item on UDI * Do you experience urine leakage related to physical activity, coughing, or sneezing? Diagnosis of SUI defined by a positive cough stress test (CST) or UDE within the past 18 months Presence of UUI on bladder diary with > 4 Urgency IE/3-day diary Urinary symptoms >3 months Persistent symptoms despite at least one or more conservative treatments (e.g. supervised behavioral therapy, physical therapy) as determined adequate by the physician. Inadequate response to oral overactive bladder medications (including anti-cholinergic and/or beta-mimetic medication) unless patient is intolerant of oral overactive bladder medications, or oral overactive bladder medications are contraindicated as determined by the treating provider. Urodynamics within past 18 months Demonstrates ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization. Exclusion Criteria: Anterior or apical compartment prolapse at or beyond the hymen (>0 on POPQ), regardless if patient is symptomatic * Women with anterior or apical prolapse above the hymen (<0) who do not report vaginal bulge symptoms will be eligible Planned concomitant surgery for anterior vaginal wall or apical prolapse > 0 * Women undergoing only rectocele repair or other repair unrelated to anterior or apical compartment are eligible Women undergoing hysterectomy for any indication will be excluded Active pelvic organ malignancy Age <21 years Pregnant or plans for future pregnancy in next 6 months, or within 12 months post-partum Post-void residual >150 cc on 2 occasions within the past 6 months, or current catheter use Participation in other trial that may influence results of this study Unevaluated hematuria Prior sling, synthetic mesh for prolapse, implanted nerve stimulator for urinary incontinence Spinal cord injury or advanced/severe neurologic conditions including Multiple Sclerosis, Parkinsons, Myasthenia Gravis, Charcot-Marie-Tooth Women on overactive bladder medication/therapy will be eligible after 3 week wash-out period Non-ambulatory History of serious adverse reaction to synthetic mesh Not able to complete study assessments per clinician judgment, or not available for 6 month follow-up Diagnosis of and/or history of bladder pain or chronic pelvic pain Women who had intravesical Botox injection within the past 12 months Women who have undergone anterior or apical pelvic organ prolapse repair within the past 6 months

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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 6 months, the effect of treatment with Botox A or mid-urethral sling will be evaluated within a classic RCT model. The analysis will determine the effect of treatment on the primary outcome, change in Urogenital Distress Inventory (UDI) score at 6 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Botox A® injection<br>A dose of 100 units of Botulinum toxin A will be injected into the bladder. Follow up visits at 2 weeks, 3 and 6 months post intervention to collect clinical and patient-reported outcomes. | Drug: Botox® injection<br>* Botulinum toxin A will be prepared by dissolving 100 units of botulinum toxin A into 10 ml of injectable saline. Indigo carmine or methylene blue 0.1 ml will be added to each syringe of botulinum toxin A. The treating physician will inject a total of 10 ml of the Botox A® into approximately 15 to 20 different detrusor muscle sites under direct visualization.<br>|
| Active Comparator: Mid-urethral sling<br>Mid-urethral Sling Procedure includes retropubic as well as transobturator full length slings. Follow up visits at 2 weeks, 3 and 6 months post intervention to collect clinical and patient-reported outcomes. | Device: Mid-urethral sling<br>* Mid-urethral Sling Procedure includes retropubic as well as transobturator full length slings. Mini-sling and single-incision sling will not be allowed due to potential risk for higher failure rate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urogenital Distress Inventory (UDI) Total Score at 6 Months | The Urogenital Distress Inventory Total Score is a standardized a measure of overactive bladder symptoms and health-related quality of life. The score ranges from 0-300 with higher scores indicating a worse outcome. The outcome is calculated as the difference in score at 6 months and the score at baseline. | Baseline until 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urogenital Distress Inventory (UDI) Stress Subscore at 6 Months | The Urogenital Distress Inventory Stress Score is a standardized a measure of stress-related overactive bladder symptoms and quality of life. The score ranges from 0-100 with higher scores indicating a worse outcome.Higher scores mean worse outcome. The outcome is calculated as the difference in the stress subscore at 6 months and the score at baseline. | Baseline until 6 months | 
| Change in Urogenital Distress Inventory (UDI) Stress Subscore at 12 Months | The Urogenital Distress Inventory Stress Score is a standardized a measure of stress-related overactive bladder symptoms and quality of life. The score ranges from 0-100 with higher scores indicating a worse outcome.Higher scores mean worse outcome. The outcome is calculated as the difference in the stress subscore at 12 months and the score at baseline. | Baseline until 12 months | 
| Change in Urogenital Distress Inventory (UDI) Irritative Sub-Score at 6 Months | The Urogenital Distress Inventory Irritative Score is a standardized a measure of irritation-related overactive bladder symptoms and quality of life. The score ranges from 0-100 with higher scores indicating a worse outcome. The outcome is calculated as the difference in the irritative subscore at 6 months and the score at baseline. | Baseline until 6 months | 
| Change in Urogenital Distress Inventory (UDI) Irritative Sub-Score at 12 Months | The Urogenital Distress Inventory Irritative Score is a standardized a measure of irritation-related overactive bladder symptoms and quality of life. The score ranges from 0-100 with higher scores indicating a worse outcome. The outcome is calculated as the difference in the irritative subscore at 12 months and the score at baseline. | Baseline until 12 months | 
| Change in Urogenital Distress Inventory (UDI) Total Score at 3 Months | The Urogenital Distress Inventory Irritative Score is a standardized a measure of irritation-related overactive bladder symptoms and quality of life. The score ranges from 0-100 with higher scores indicating a worse outcome. The outcome is calculated as the difference in the irritative subscore at 3 months and the score at baseline. | Baseline until 3 months | 
| Change in Urogenital Distress Inventory (UDI) Total Score at 12 Months | The Urogenital Distress Inventory Total Score is a standardized a measure of overactive bladder symptoms and health-related quality of life. The score ranges from 0-300 with higher scores indicating a worse outcome. The outcome is calculated as the difference in score at 12 months and the score at baseline. | Baseline until 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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urinary incontinence, midurethral sling, Botulinum toxin A (Botox A ®)