Sling vs Botox for Mixed Incontinence

NCT04171531 | Completed Phase 3 Results DMC FDA Drug

• 9 other identifiers: PFDN-31P01U24HD069031-06UG1HD069013-06UG1HD041267-18UG1HD069010-07UG1HD069006-07UG1HD041261-17UG1HD054214-12UG1HD054241-12
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 8

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.

Conditions

Urinary Incontinence, Stress; Urinary Incontinence, Urge

Keywords

urinary incontinence; midurethral sling; Botulinum toxin A (Botox A ®)

Outcome Measures

Primary Outcomes (1)

• UDI-LF Total Score Change From Baseline

  The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI scale has a range from 0 to 300 with higher scores indicating greater distress. The outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline.

  3, 6, 9, and 12 Months

Secondary Outcomes (2)

• UDI-LF Stress Score Change From Baseline

  3, 6, 9, and 12 Months

• UDI-LF Irritative Score Change From Baseline

  3, 6, 9, and 12 Months

Other Outcomes (52)

• UDI-LF Obstructive Score Change From Baseline

  3, 6, 9, and 12 Months

• Average Daily Frequency of Combined Mixed Stress/Urge and Non-categorized Incontinence Epsiodes Change From Baseline

  3, 6, and 12 Months

• Average Daily Frequency of All Incontinence Epsiodes Change From Baseline

  3, 6, and 12 Months

Study Arms (2)

Botox A® injection

ACTIVE COMPARATOR

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

Mid-urethral sling

ACTIVE COMPARATOR

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

Interventions

Botox® injection DRUG

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.

Botox A® injection

Mid-urethral sling DEVICE

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.

Mid-urethral sling

Eligibility Criteria

• Age: 21 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (8)

University of Alabama at Birmingham, Department of Obstetrics and Gynecology

Birmingham, Alabama, 35249, United States

Location

University of California at San Diego

La Jolla, California, 92037-0974, United States

Location

Kaiser Permanente

San Diego, California, 92110, United States

Location

Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery

Durham, North Carolina, 27707, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Magee-Women's Hospital, Department of Obstetrics and Gynecology

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery

Providence, Rhode Island, 02903, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (3)

• Harvie HS, Menefee SA, Richter HE, Sung VW, Chermansky CJ, Rahn DD, Amundsen CL, Arya LA, Rhodes E, Mazloomdoost D, Thomas S; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Midurethral Sling vs OnabotulinumtoxinA in Females With Urinary Incontinence: The MUSA Randomized Clinical Trial. JAMA. 2025 Jun 3;333(21):1887-1896. doi: 10.1001/jama.2025.4682.

  PMID: 40323617 DERIVED

• Harvie HS, Richter HE, Sung VW, Chermansky CJ, Menefee SA, Rahn DD, Amundsen CL, Arya LA, Huitema C, Mazloomdoost D, Thomas S; NICHD Pelvic Floor Disorders Network. Trial Design for Mixed Urinary Incontinence: Midurethral Sling Versus Botulinum Toxin A. Urogynecology (Phila). 2024 May 1;30(5):478-488. doi: 10.1097/SPV.0000000000001422. Epub 2024 Jan 11.

  PMID: 38212101 DERIVED

• 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.

  PMID: 34242627 DERIVED

MeSH Terms

Conditions

Urinary Incontinence, Stress; Urinary Incontinence, Urge; Urinary Incontinence

Interventions

Botulinum Toxins, Type A; Suburethral Slings

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Prostheses and Implants; Equipment and Supplies

Results Point of Contact

• Title: Marie Gantz
• Organization: RTI International

mgantz@rti.org

919-541-5110

Study Officials

• Heidi S Harvey, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Marie Gantz, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 21, 2019
• Study Start: June 8, 2020
• Primary Completion: February 12, 2024
• Study Completion: February 12, 2024
• Last Updated: June 3, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)