Combined Treatment for Mixed Incontinence (ESTEEM)
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.
|Urinary Incontinence, Stress Urinary Incontinence, Urge||Procedure: Miduretheral Sling Other: Miduretheral Sling with behavioral/pelvic floor therapy||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Treatment
|Official Title:||Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence (ESTEEM)|
- Severity of MUI symptoms [ Time Frame: 3, 6, and 12 month visits ]Change from baseline in severity of MUI symptoms at 1 year following MUS measured using the Urogenital Distress Inventory (UDI).
- OAB symptom outcomes [ Time Frame: 3, 6, 12 month visits ]To assess whether combined MUS+BPTx is superior to MUS alone for improving change in OAB symptoms at 1 year in women electing surgical treatment. OAB symptoms will be measured using Urogenital Distress Inventory (UDI)-irritative subscale scores
- SUI symptom outcomes [ Time Frame: 3, 6, 12 month visits ]To assess whether combined MUS+BPTx is superior to MUS alone for improving change in SUI symptoms at 1 year in women electing surgical treatment for MUI. SUI symptoms will be measured using the UDI-stress subscale.
- Secondary urinary outcomes [ Time Frame: 3, 6, and 12 month visit ]To assess whether combined MUS+BPTx is superior to MUS alone for improving the number of urgency and urge incontinence episodes (IEs) on bladder diary at 1 year following MUS surgery.
- Time to failure [ Time Frame: Up until 12 month visit ]To compare time to failure between MUS+BPTx versus MUS alone. Failure will be defined as initiation of any additional treatment for lower urinary tract symptoms (SUI, urge urinary incontinence (UUI)/OAB, or voiding dysfunction).
- Predictors of poor outcomes [ Time Frame: 3, 6, and 12 month visits ]To develop models to identify predictors of change of MUI, OAB, and SUI outcomes measured using the UDI between baseline and 1 year post-treatment.
- Quality of life and global impression [ Time Frame: 3, 6, and 12 month visits ]To compare quality of life outcomes and Patient Global Impression-Improvement (PGI-I), Patient Global Impression-Severity (PGI-S) between groups.
- Safety and additional treatments [ Time Frame: Up until 12 month visit ]To describe rates of reoperation (sling revision) for worsening OAB symptoms after MUS and to compare the proportion of women in each group initiating additional treatment for SUI and/or OAB, and the types of additional treatment (BPTx, medications, other).
- Minimally important difference (MID) and clinical definitions [ Time Frame: 3, 6, and 12 month visits ]To determine MIDs and clinically meaningful definitions of MUI that predict clinical outcomes using cut-offs and combinations of standardized measures
- Pelvic floor muscle (PFM) strengthening [ Time Frame: Baseline, 2 and 8 weeks, 12 months ]To compare pelvic floor muscle strength changes between women randomized to combined MUS+BPTx versus MUS alone and to estimate associations between pelvic floor muscle strength improvement and urinary incontinence symptoms. We will also explore predictors of unsuccessful pelvic floor muscle strengthening.
- Cost-effectiveness analysis [ Time Frame: Up until 12 month visit ]To determine the cost effectiveness of combined MUS and peri-operative BPTx compared to MUS alone for the treatment of MUI symptoms
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
Sham Comparator: Miduretheral Sling (Control)
Miduretheral Sling (Control)
Procedure: Miduretheral Sling
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).
Other Name: MUS
Miduretheral Sling with behavioral/pelvic floor therapy
Other: Miduretheral Sling with behavioral/pelvic floor therapy
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.
Other Name: MUS + BPTx
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01959347
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01959347
|United States, Alabama|
|University of Alabama at Birmingham, Department of Obstetrics and Gynecology|
|Birmingham, Alabama, United States, 35249-7333|
|United States, California|
|Kaiser Permanente -- Downey|
|Downey, California, United States, 90242|
|University of California at San Diego, UCSD Women's Pelvic Medicine Center|
|La Jolla, California, United States, 92037-0974|
|Kaiser Permanente -- San Diego|
|San Diego, California, United States, 92110|
|United States, New Mexico|
|University of New Mexico Health Sciences Center, Department of Obstetrics and Gynecology|
|Albuquerque, New Mexico, United States, 87131-0001|
|United States, North Carolina|
|Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery|
|Durham, North Carolina, United States, 27707|
|United States, Ohio|
|Cleveland Clinic, Department OB/GYN|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Magee-Womens Hospital, Department of Obstetrics and Gynecology|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Rhode Island|
|Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery|
|Providence, Rhode Island, United States, 02903|
|Principal Investigator:||Vivian W. Sung||Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery|
|Principal Investigator:||Dennis Wallace||RTI International|