Combined Treatment for Mixed Incontinence

Study Overview
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Brief Summary
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The overarching goal of this randomized trial is to estimate the effect of combined midurethral sling (MUS) and peri-operative behavioral/pelvic floor therapy (BPTx) compared to MUS alone on successful treatment of MUI symptoms in 472 women. Secondary objectives include estimating the effect of combined treatment compared to MUS on improving overactive bladder (OAB) and stress urinary incontinence (SUI) outcomes separately, need for additional treatment, time to failure and identifying predictors of poor outcomes in this MUI population. A supplemental study, The Human Microbiome Study of ESTEEM, will evaluate the urinary and vaginal microbiome as it relates to women with MUI, their treatment and unaffected controls.

Detailed Description
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ESTEEM is a multi-center randomized trial of 472 women with MUI who have elected to undergo surgical treatment for SUI. Participants will be randomized to a peri-operative BPTx program+MUS versus MUS alone. The purpose is to compare combined MUS+BPTx versus MUS alone (control) on improving MUI symptoms at 1 year. Patients will be assigned to one of the two treatment groups. Randomization will be stratified by clinical site and by UUI severity, which will be defined by the number of urgency urinary IEs on diary. The primary outcome for this study is the mean change from baseline in UDI-total score at 1 year postoperative. The UDI is a validated, disease-specific, patient-reported outcome (PRO) measure. Secondary outcomes UUI/OAB outcomes will be measured using the UDI-irritative subscale that measures symptom burden, impact, and changes related to OAB. It is highly responsive to treatment-related change and is able to discriminate among levels of change in all bladder diary variables (urinary urgency, frequency and urge incontinence) and patient ratings of treatment benefit that will characterize how MUS may affect all OAB symptoms individually and as a whole. SUI symptom outcomes will be measured using the UDI-stress subscale to compare SUI outcomes between women randomized to MUS + BPTx versus MUS alone. Other UUI/OAB outcomes that will be compared between groups include 1) the change in IE frequency and type, number of urgency episodes, urgency severity with voids, number of diurnal voids, and number of nocturnal voids using a bladder diary; 2) patient satisfaction with treatment using the OAB-SAT-q; 3) bother and heal related quality of life using the OAB-q subscale For analyzing time to failure, failure will be defined as initiation of any additional treatment for either SUI or UUI/OAB symptoms during the follow-up period. Subjects lost to follow up will be censored at the time of their last visit. Quality of life/global impression will be assessed be compared between treatment groups using the a) Incontinence Impact Questionnaire (IIQ), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ), c) European Quality of Life-5 Dimensions (EQ-5D), d) Adaptation Index and e) Patient Global Impression of Improvement (PGI-I) and Patient Global Impression of Severity (PGI-S). Safety/additional treatments will be characterized as a) additional re-treatments for SUI or UUI within 12 months of treatment, and type of re-treatment and b) return to OR for sling revision due to worsened OAB symptoms. To evaluate the association between PFM strength and improvements in UI symptoms, we will objectively assess PFM strength changes using the Peritron Perineometer, and instrument specifically designed for pelvic floor assessment.

Official Title
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Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence (ESTEEM)

Conditions
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Urinary Incontinence, Stress, Urinary Incontinence, Urge

Intervention / Treatment
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* Procedure: Miduretheral Sling
* Other: Miduretheral Sling with behavioral/pelvic floor therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of both SUI and UUI on bladder diary; and > 2 IEs/3 days > 1 Stress IE/3 day diary > 1 Urge IE/3 day diary Reporting at least moderate bother from UUI item on the 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? Reporting at least moderate bother from SUI item on UDI Do you usually experience urine leakage related to coughing, sneezing, or laughing Diagnosis of SUI defined by a positive cough stress test (CST) or urodynamic evaluation within the past 18 months Desires surgical treatment for SUI symptoms Urinary symptoms >3 months Subjects understand that BPTx is a treatment option for MUI outside of ESTEEM study protocol Urodynamics within past 18 months Exclusion Criteria: Anterior or apical compartment prolapse at or beyond the hymen (>0 on POPQ), regardless if patient is symptomatic a)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 a)Women undergoing only rectocele repair 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 12 months, or within 12 months post-partum Post-void residual >150 cc on 2 occasions, 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 incontinence Spinal cord injury or advanced/severe neurologic conditions including Multiple Sclerosis, Parkinsons Women on anti-muscarinic therapy will be eligible after 3 week wash-out period Non-ambulatory History of serious adverse reaction to synthetic mesh Not able to complete study assessments per clinician judgment, or not available for 12 month follow-up Women who only report other IE on bladder diary, and do not report at minimum 1 stress and 1 urge IE/3 days Diagnosis of and/or history of bladder pain or chronic pelvic pain Women who had intravesical Botox injection within the past 12 months

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Miduretheral Sling (Control)<br>Miduretheral Sling (Control) | Procedure: Miduretheral Sling<br>* MUS can include the TVT™ (mechanical cut mesh only, Gynecare, ETHICON Women's Health & Urology, Somerville, NJ), TVT-O™ (mechanical cut mesh only, Gynecare), or Monarc™ (American Medical Systems, Minnetonka, MN).<br>* Other names: MUS;|
| Experimental: MUS+BPTx<br>Miduretheral Sling with behavioral/pelvic floor therapy | Other: Miduretheral Sling with behavioral/pelvic floor therapy<br>* MUS is combined with components of behavioral therapy (designed to change behaviors to encourage continence), and pelvic floor muscle therapy (designed to strengthen the pelvic floor muscles, enhance the physiological closure of the bladder neck, and improve coordination). This is done prior to MUS (1 visit) and after MUS for 5 visits at 2, 4, 6, 8 weeks and 6 months.<br>* Other names: MUS + BPTx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline UDI Total Score | The Urogenital Distress Inventory (UDI) 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 change from baseline outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline. | 3, 6, and 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline UDI Stress Score | The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI Stress subscale has a range from 0 to 100 with higher scores indicating greater distress. The change from baseline outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline. | 3, 6, and 12 Months | 
| Change From Baseline UDI Irritative Score | The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI Irritative subscale has a range from 0 to 100 with higher scores indicating greater distress. The change from baseline outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline. | 3, 6, and 12 Months | 
| Change From Baseline UDI Obstructive Score | The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI Obstructive subscale has a range from 0 to 100 with higher scores indicating greater distress. The change from baseline outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline. | 3, 6, and 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pelvic floor therapy, urinary incontinence, midurethral sling