Sling vs Botox for Mixed Incontinence (MUSA)

NICHD Pelvic Floor Disorders Network

Status and phase: Completed; Phase 3

Conditions: Urinary Incontinence, Stress; Urinary Incontinence, Urge

Treatments: Device: Mid-urethral sling; Drug: Botox® injection

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT04171531

PFDN-31P01

UG1HD054241-12 (U.S. NIH Grant/Contract)

U24HD069031-06 (U.S. NIH Grant/Contract)

UG1HD054214-12 (U.S. NIH Grant/Contract)

UG1HD069006-07 (U.S. NIH Grant/Contract)

UG1HD069010-07 (U.S. NIH Grant/Contract)

UG1HD041267-18 (U.S. NIH Grant/Contract)

UG1HD069013-06 (U.S. NIH Grant/Contract)

UG1HD041261-17 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 patients

Sex: Female

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

Botox A® injection

Active Comparator group

Description:

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.

Treatment:

Drug: Botox® injection

Mid-urethral sling

Active Comparator group

Description:

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.

Treatment:

Device: Mid-urethral sling