Sling vs Botox for Mixed Incontinence

Urinary Incontinence, Stress Clinical Trial

— MUSA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04171531
• Other study ID #: PFDN-31P01
• Secondary ID: U24HD069031-06UG
• Status: Completed
• Phase: Phase 3
• Start date: June 8, 2020
• Est. completion date: February 12, 2024

Study information

• Verified date: April 2024
• Source: NICHD Pelvic Floor Disorders Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: February 12, 2024
• Est. primary completion date: February 12, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Reporting at least "moderate bother" from UUI item on UDI

• "Do you experience urine leakage associated with a feeling of urgency?"

2. Reporting at least "moderate bother" from SUI item on UDI

• "Do you experience urine leakage related to physical activity, coughing, or sneezing?"

3. Diagnosis of SUI defined by a positive cough stress test (CST) or UDE within the past 18 months

4. Presence of UUI on bladder diary with > 4 Urgency IE/3-day diary

5. Urinary symptoms >3 months

6. Persistent symptoms despite at least one or more conservative treatments (e.g. supervised behavioral therapy, physical therapy) as determined adequate by the physician.

7. Inadequate response to oral overactive bladder medications (including anti-cholinergic and/or beta-mimetic medication) unless patient is

1. intolerant of oral overactive bladder medications, or

2. oral overactive bladder medications are contraindicated as determined by the treating provider.

8. Urodynamics within past 18 months

9. Demonstrates ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization.

Exclusion Criteria:

1. 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

2. 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

3. Women undergoing hysterectomy for any indication will be excluded

4. Active pelvic organ malignancy

5. Age <21 years

6. Pregnant or plans for future pregnancy in next 6 months, or within 12 months post-partum

7. Post-void residual >150 cc on 2 occasions within the past 6 months, or current catheter use

8. Participation in other trial that may influence results of this study

9. Unevaluated hematuria

10. Prior sling, synthetic mesh for prolapse, implanted nerve stimulator for urinary incontinence

11. Spinal cord injury or advanced/severe neurologic conditions including Multiple Sclerosis, Parkinsons, Myasthenia Gravis, Charcot-Marie-Tooth

12. Women on overactive bladder medication/therapy will be eligible after 3 week wash-out period

13. Non-ambulatory

14. History of serious adverse reaction to synthetic mesh

15. Not able to complete study assessments per clinician judgment, or not available for 6 month follow-up

16. Diagnosis of and/or history of bladder pain or chronic pelvic pain

17. Women who had intravesical Botox injection within the past 12 months

18. Women who have undergone anterior or apical pelvic organ prolapse repair within the past 6 months

Related Conditions & MeSH terms

• Enuresis
• Urinary Incontinence
• Urinary Incontinence, Stress
• Urinary Incontinence, Urge

Intervention

Drug:
• Botox® injection
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.

Device:
• Mid-urethral sling
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.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham, Department of Obstetrics and Gynecology	Birmingham	Alabama
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery	Durham	North Carolina
United States	University of California at San Diego	La Jolla	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Magee-Women's Hospital, Department of Obstetrics and Gynecology	Pittsburgh	Pennsylvania
United States	Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery	Providence	Rhode Island
United States	Kaiser Permanente	San Diego	California

Sponsors (11)

Lead Sponsor	Collaborator
NICHD Pelvic Floor Disorders Network	Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Kaiser Permanente, RTI International, University of Alabama at Birmingham, University of California, San Diego, University of Pennsylvania, University of Pittsburgh, University of Texas Southwestern Medical Center, Women and Infants Hospital of Rhode Island

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline Total Number of Incontinence Episodes	Based on data collected from participant-completed diaries at baseline and 6 months, the outcome variable is computed as the difference in total number of incontinence episodes at 6 months and the total number of incontinence episodes at baseline. Higher counts mean worse outcome.	Baseline until 6 months
Other	Change in Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Satisfaction Score	The Overactive Bladder Satisfaction with Treatment Questionnaire Satisfaction Score is a standardized a measure of satisfaction with treatment for overactive bladder symptoms. The score ranges from 0-100 with higher scores indicating a better outcome. The outcome is calculated as a difference between 3 and 6 months.	3 months until 6 months
Other	Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Side Effect Score	The Overactive Bladder Satisfaction with Treatment Questionnaire Side Effect Score is a standardized a measure of the impact of side effects from treatment for overactive bladder symptoms. The score ranges from 0-100 with higher scores indicating a better outcome. The outcome is calculated as a difference between 3 and 6 months.	3 months until 6 months
Other	Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Endorsement Score	The Overactive Bladder Satisfaction with Treatment Questionnaire Endorsement Score is a standardized a measure of endorsement of treatment for overactive bladder symptoms. The score ranges from 0-100 with higher scores indicating a better outcome. The outcome is calculated as a difference between 3 and 6 months.	3 months until 6 months
Other	Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Convenience Score	The Overactive Bladder Satisfaction with Treatment Questionnaire Convenience Score is a standardized a measure of convenience of treatment for overactive bladder symptoms. he score ranges from 0-100 with higher scores indicating a better outcome. The outcome is calculated as a difference between 3 and 6 months.	3 months until 6 months
Other	Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Preference Score	The Overactive Bladder Satisfaction with Treatment Questionnaire Preference Score is a standardized a measure preference for treatment for overactive bladder symptoms. It is calculated as the percent of respondents who respond "Slight" or "Definite" preference for a new treatment among those respondents who have had previous treatment for overactive bladder. The score ranges from 0-100 with higher scores indicating a better outcome. The outcome is calculated as a difference between 3 and 6 months.	3 months until 6 months.
Other	Overactive Bladder Questionnaire-Long Form (OABq-LF) Symptom Severity Score	The Overactive Bladder Questionnaire-Long Form Symptom Severity Score is a standardized a measure of the severity of 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 change from baseline in scores at 3 months and 6 months.	Baseline until 6 months
Other	Patient Global Impression of Improvement (PGI-I)	The Patient Global Impression of Improvement (PGI-I) is a patient-reported measure of perceived improvement with treatment, as assessed on a scale of 1 (very much better) to 7 (very much worse). Included here are participants who had improvement as indicated by a rating of 1 (very much better), 2 (much better). The outcome is calculated as the difference between 3 months and 6 months.	3 months until 6 months
Other	The Patient Global Impression of Severity (PGI-S)	The Patient Global Impression of Severity (PGI-S) is a patient-reported measure of perceived severity of condition, as assessed on a scale of 1 (Normal) to 4 (Severe). Included here are participants who reported Normal or Mild severity as indicated by a rating of 1 or 2. The outcome is calculated as the difference between baseline and 6 months.	Baseline until 6 months
Other	Incontinence Impact Questionnaire-Long Form (IIq-LF) Total Score	The Incontinence Impact Questionnaire-Long Form is a standardized a measure of health-related quality of life. The score ranges from 0-400 with higher scores indicating a worse outcome. The outcome is calculated as the difference in score at 3 months and 6 months.	3 months until 6 months
Other	Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA Revised (PISQ-IR) Sexually Active Average Score	The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA Revised Sexually Active Average Score Form is a standardized a measure of sexual function in women with pelvic organ prolapse or urinary incontinence. The score ranges from 1-5 with higher scores indicating better sexual functioning. The outcome is calculated as the difference in score at 3 months and 6 months.	3 months and 6 months
Other	European Quality of Life-5 Dimensions (EQ-5D) Index Score	EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life. The score ranges from 0-1 with higer scores indicating better outcome. The outcome is calculated as the difference in score at 3 months and 6 months.	3 months and 6 months
Other	European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale Score	EQ-5D is a standardized instrument developed by the EuroQol Group as a patient-reported measure of health-related quality of life. The score ranges from 0-100 with higher scores meaning better outcome. The outcome is calculated as the difference in score at 3 months and 6 months.	3 months and 6 months
Other	Short-Form Health Survey (SF-36) - Scores	The SF-36 is a multi-purpose, short-form health survey with 36 questions providing a score for physical and mental health summary measures. The scores range from 0-100 with higher scores indicating better outcomes. The outcome is calculated as the difference in score at 3 months and 6 months.	3 months and 6 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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