Clinical trial NCT04171531: Sling vs Botox for Mixed Incontinence
Official title: Treatment for Mixed Urinary Incontinence: Mid-urethral Sling vs. Botox A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Incontinence, Stress
Urinary Incontinence, Urge
Keywords: urinary incontinence
midurethral sling
Botulinum toxin A (Botox A ®)
Lead sponsor: NICHD Pelvic Floor Disorders Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Women and Infants Hospital of Rhode Island
name: Duke University
name: University of Pennsylvania
name: University of Pittsburgh
name: University of California, San Diego
name: Kaiser Permanente
name: University of Texas Southwestern Medical Center
name: University of Alabama at Birmingham
name: RTI International
First posted: 2019-11-21
Enrollment: 150
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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 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 outcomes include:

• Urogenital Distress Inventory Stress and Irritative subscales

Other outcomes include:

* Urogenital Distress Inventory Obstructive subscale
* Patient bladder diary metrics including numbers of daily incontinence episodes and voids and voiding frequency
* Other patient reported outcomes/validated instruments and associated scales and subscales: EQ-5D, IIQ-LF, OABq-LF, OAB-SATq, PISQ-IR, PGI-I, PGI-S, PGSC, and SF-36
* Physical measures of effectiveness: Postvoid Residual Volume

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. Those results are not reported with this record.

Eligibility criteria: 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

Primary outcomes:
measure: UDI-LF Total Score Change From Baseline
timeFrame: 3, 6, 9, and 12 Months
Secondary outcomes:
measure: UDI-LF Stress Score Change From Baseline
timeFrame: 3, 6, 9, and 12 Months
measure: UDI-LF Irritative Score Change From Baseline
timeFrame: 3, 6, 9, and 12 Months
Other outcomes:
measure: UDI-LF Obstructive Score Change From Baseline
timeFrame: 3, 6, 9, and 12 Months
measure: Average Daily Frequency of Combined Mixed Stress/Urge and Non-categorized Incontinence Epsiodes Change From Baseline
timeFrame: 3, 6, and 12 Months
measure: Average Daily Frequency of All Incontinence Epsiodes Change From Baseline
timeFrame: 3, 6, and 12 Months
measure: Average Daily Frequency of Diurnal Voids Change From Baseline
timeFrame: 3, 6, and 12 Months
measure: Average Daily Frequency of Nocturnal Voids Change From Baseline
timeFrame: 3, 6, and 12 Months
measure: Average Daily Frequency of All Voids Change From Baseline
timeFrame: 3, 6, and 12 Months
measure: Normalization of Voiding Frequency
timeFrame: 3, 6, and 12 Months
measure: Improvement of 50% or More in Voiding Frequency Post Baseline
timeFrame: 3, 6, and 12 Months
measure: Worsening Voiding Frequency Post Baseline
timeFrame: 3, 6, and 12 Months
measure: Change From Baseline EQ-5D Visual Analog Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, and 12 Months
measure: Change From Baseline EQ-5D Index Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, and 12 Months
measure: Change From Baseline IIQ-LF Physical Activity Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline IIQ-LF Travel Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline IIQ-LF Social/Relationships Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline IIQ-LF Emotional Health Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline IIQ-LF Total Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline OABq-LF Symptom Severity Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline OABq-LF Coping Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline OABq-LF Concern Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline OABq-LF Sleep Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline OABq-LF Social Score
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline OABq-LF HRQL Total Score
timeFrame: 3, 6, 9, and 12 Months
measure: OAB-SATq-LF Satisfaction Score
timeFrame: 3, 6, 9, and 12 Months
measure: OAB-SATq-LF Side Effects Score
timeFrame: 3, 6, 9, and 12 Months
measure: OAB-SATq-LF Endorsement Score
timeFrame: 3, 6, 9, and 12 Months
measure: OAB-SATq-LF Convenience Score
timeFrame: 3, 6, 9, and 12 Months
measure: OAB-SAT-q Preference Indicator
timeFrame: 3, 6, 9, and 12 Months
measure: PGI-I Score Binary Improvement Indicator
timeFrame: 3, 6, 9, and 12 Months
measure: PGI-S Score Binary Condition Severity Indicator
timeFrame: Baseline and 3, 6, 9, and 12 Months
measure: PGSC Score Binary Improvement Indicator
timeFrame: 3, 6, 9, and 12 Months
measure: Change From Baseline PISQ-IR NSA-PR Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR NSA-CS Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR NSA-GQA Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR NSA-CI Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA-AO Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA-PR Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA-CS Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA-GQR Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA-CI Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA-D Score
timeFrame: 3, 6, 9, and 12 months
measure: Change From Baseline PISQ-IR SA Average Score
timeFrame: 3, 6, 9, and 12 months
measure: SF-36 Physical Functioning Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Role Physical Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Bodily Pain Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 General Health Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Vitality Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Social Functioning Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Emotional Role Limitations Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Mental Health Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Physical Composite Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: SF-36 Mental Composite Score
timeFrame: 0.5 Months (2 Weeks) and 3, 6, 9, and 12 months
measure: Postvoid Residual Volume
timeFrame: Baseline, 3, 6, and 12 Months
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Department of Obstetrics and Gynecology
state: Alabama
city: La Jolla
country: United States
facility: University of California at San Diego
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: Durham
country: United States
facility: Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Women's Hospital, Department of Obstetrics and Gynecology
state: Pennsylvania
city: Providence
country: United States
facility: Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Pennsylvania
name: Heidi S Harvey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Marie Gantz, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harvie HS, Sung VW, Neuwahl SJ, Honeycutt AA, Meyer I, Chermansky CJ, Menefee S, Hendrickson WK, Dunivan GC, Mazloomdoost D, Bass SJ, Gantz MG; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Cost-effectiveness of behavioral and pelvic floor muscle therapy combined with midurethral sling surgery vs surgery alone among women with mixed urinary incontinence: results of the Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence randomized trial. Am J Obstet Gynecol. 2021 Dec;225(6):651.e1-651.e26. doi: 10.1016/j.ajog.2021.06.099. Epub 2021 Jul 6.