Treatment for Mixed Urinary Incontinence: Mid-urethral Sling vs. Botox A
Sling vs Botox for Mixed Incontinence
Sponsors
Lead Sponsor
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 
, Women and Infants Hospital of Rhode Island , Duke University , University of Pennsylvania , University of Pittsburgh , University of California, San Diego , Kaiser Permanente , University of Texas Southwestern Medical Center , University of Alabama at Birmingham , RTI International
, Women and Infants Hospital of Rhode Island , Duke University , University of Pennsylvania , University of Pittsburgh , University of California, San Diego , Kaiser Permanente , University of Texas Southwestern Medical Center , University of Alabama at Birmingham , RTI International Source
NICHD Pelvic Floor Disorders Network
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
Is Us Export
No
Brief Summary
The primary aim is to determine whether a single 100 unit injection of Botulinum toxin A is
superior to mid-urethral sling for improving MUI symptoms 3 months following treatment.
Detailed 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 140 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 Botulinum toxin A (Botox A ®) compared to
mid-urethral sling for treatment of MUI in 140 women 3 months after treatment. The change in
severity of MUI symptoms will be measured using the Urogenital Distress Inventory.1
Secondary objectives include identifying predictors of treatment failure and
cost-effectiveness of treatments in this MUI population.
Overall Status
Not yet recruiting
Start Date
2020-04-01
Completion Date
2023-05-01
Primary Completion Date
2023-05-01
Phase
Phase 3
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Change in Urogenital Distress Inventory (UDI) Total Score |
Baseline until 3 months |
Secondary Outcome
Measure |
Time Frame |
|
Change in Urogenital Distress Inventory (UDI) Stress Subscore |
Baseline until 3 months |
|
Change in Urogenital Distress Inventory (UDI) Irritative Sub-Score |
Baseline until 3 months |
Enrollment
140
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Botox A® injection
Intervention Type
Device
Intervention Name
Description
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.
Arm Group Label
Mid-urethral sling
Eligibility
Criteria
Inclusion Criteria:
1. Reporting at least "moderate bother" from UUI item on UDI
* "Do you usually experience urine leakage associated with a feeling of urgency, that
is a strong sensation of needing to go to the bathroom?"
2. Reporting at least "moderate bother" from SUI item on UDI
* "Do you usually experience urine leakage related to coughing, sneezing, or laughing"
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)
7. Urodynamics within past 18 months
8. 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 3 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, Myasthesia Gravis, Marie-charcot-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 3
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
Gender
Female
Gender Based
Yes
Minimum Age
21 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Heidi S Harvey, MD |
Principal Investigator |
University of Pennsylvania |
|
Marie Gantz, PhD |
Principal Investigator |
RTI International |
Location
Facility |
Status |
Contact |
Investigator |
|
University of Alabama at Birmingham, Department of Obstetrics and Gynecology Birmingham Alabama 35249 United States |
Not yet recruiting |
Last Name: Holly E Richter, PhD, MD Role: Principal Investigator | |
|
University of California at San Diego La Jolla California 92037-0974 United States |
Not yet recruiting |
Last Name: Emily Lukacz, MD Role: Principal Investigator | |
|
Kaiser Permanente San Diego California 92110 United States |
Not yet recruiting |
Last Name: Shawn Menefee Role: Principal Investigator | |
|
Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery Durham North Carolina 27707 United States |
Not yet recruiting |
Last Name: Anthony G Visco, MD Role: Principal Investigator | |
|
University of Pennsylvania Philadelphia Pennsylvania 19104 United States |
Not yet recruiting |
Last Name: Heidi Harvie, MD Role: Principal Investigator | |
|
Magee-Women's Hospital, Department of Obstetrics and Gynecology Pittsburgh Pennsylvania 15213 United States |
Not yet recruiting |
Last Name: Halina M Zyczynski, MD Role: Principal Investigator | |
|
Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery Providence Rhode Island 02903 United States |
Not yet recruiting |
Last Name: Vivian Sung, MD Role: Principal Investigator | |
|
University of Texas Southwestern Medical Center Dallas Texas 75390 United States |
Not yet recruiting |
Location Countries
Country
United States
Verification Date
2019-11-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
U24HD069031-06
UG1HD069013-06
UG1HD041267-18
UG1HD069010-07
UG1HD069006-07
UG1HD041261-17
UG1HD054214-12
UG1HD054241-12
Number Of Arms
2
Intervention Browse
Mesh Term
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
Arm Group
Arm Group Label
Botox A® injection
Arm Group Type
Active Comparator
Description
A dose of 100 units of Botulinum toxin A will be injected into the bladder. Follow up visits at 2 weeks and 3 months post intervention to collect clinical and patient-reported outcomes.
Arm Group Label
Mid-urethral sling
Arm Group Type
Active Comparator
Description
Mid-urethral Sling Procedure includes retropubic as well as transobturator full length slings. Follow up visits at 2 weeks and 3 months post intervention to collect clinical and patient-reported outcomes.
Firstreceived Results Date
N/A
Acronym
MUSA
Other Outcome
Measure
Change from baseline Total Number of Incontinence Episodes
Time Frame
Baseline until 3 months
Description
Based on data collected from participant-completed diaries at baseline and 3 months, the outcome variable is computed as the difference in total number of incontinence episodes at 3 months and the total number of incontinence episodes at baseline. Higher counts mean worse outcome.
Measure
Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Satisfaction Score
Time Frame
3 months
Description
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.
Measure
Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Side Effect Score
Time Frame
3 months
Description
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.
Measure
Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Endorsement Score
Time Frame
3 months
Description
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.
Measure
Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Convenience Score
Time Frame
3 months
Description
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
Measure
Overactive Bladder Satisfaction with Treatment Questionnaire (OAB-SATq) Preference Score
Time Frame
3 months
Description
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
Measure
Overactive Bladder Questionnaire-Long Form (OABq-LF) Symptom Severity Score
Time Frame
Baseline until 3 months
Description
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 difference in score at 3 months and the score at baseline.
Measure
Patient Global Impression of Improvement (PGI-I)
Time Frame
3 months
Description
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).
Measure
The Patient Global Impression of Severity (PGI-S)
Time Frame
Baseline until 3 months
Description
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.
Measure
Incontinence Impact Questionnaire-Long Form (IIq-LF) Total Score
Time Frame
Baseline until 3 months
Description
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 the score at baseline.
Measure
Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA Revised (PISQ-IR) Sexually Active Average Score
Time Frame
Baseline until 3 months
Description
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 the score at baseline.
Measure
European Quality of Life-5 Dimensions (EQ-5D) Index Score
Time Frame
Baseline until 3 months
Description
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 the score at baseline.
Measure
European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale Score
Time Frame
Baseline until 3 months
Description
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 the score at baseline.
Measure
Short-Form Health Survey (SF-36) - Scores
Time Frame
Baseline until 3 months
Description
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 the score at baseline.
Patient Data
Sharing Ipd
Yes
Ipd Description
Data sharing according to the NIH Policy
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
At 3 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 3 months.
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
November 18, 2019
Study First Submitted Qc
November 19, 2019
Study First Posted
November 21, 2019
Last Update Submitted
November 20, 2019
Last Update Submitted Qc
November 20, 2019
Last Update Posted
November 22, 2019
ClinicalTrials.gov processed this data on December 13, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.