Combined Treatment for Mixed Incontinence

NCT ID: NCT01959347

Last Updated: 2020-05-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

480 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-28

Study Completion Date

2017-09-29

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.

Conditions

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Urinary Incontinence, Stress Urinary Incontinence, Urge

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Caregivers

Study Groups

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Miduretheral Sling (Control)

Miduretheral Sling (Control)

Group Type SHAM_COMPARATOR

Miduretheral Sling

Intervention Type PROCEDURE

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).

MUS+BPTx

Miduretheral Sling with behavioral/pelvic floor therapy

Group Type EXPERIMENTAL

Miduretheral Sling with behavioral/pelvic floor therapy

Intervention Type OTHER

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.

Interventions

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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).

Intervention Type PROCEDURE

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.

Intervention Type OTHER

Other Intervention Names

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MUS MUS + BPTx

Eligibility Criteria

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Inclusion Criteria

1. Presence of both SUI and UUI on bladder diary; and \> 2 IEs/3 days

1. \> 1 Stress IE/3 day diary
2. \> 1 Urge IE/3 day diary
2. 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?"
3. Reporting at least "moderate bother" from SUI item on UDI "Do you usually experience urine leakage related to coughing, sneezing, or laughing"
4. Diagnosis of SUI defined by a positive cough stress test (CST) or urodynamic evaluation within the past 18 months
5. Desires surgical treatment for SUI symptoms
6. Urinary symptoms \>3 months
7. Subjects understand that BPTx is a treatment option for MUI outside of ESTEEM study protocol
8. Urodynamics within past 18 months

Exclusion Criteria

1. 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
2. Planned concomitant surgery for anterior vaginal wall or apical prolapse \> 0

a)Women undergoing only rectocele repair 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 12 months, or within 12 months post-partum
7. Post-void residual \>150 cc on 2 occasions, 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 incontinence
11. Spinal cord injury or advanced/severe neurologic conditions including Multiple Sclerosis, Parkinsons
12. Women on anti-muscarinic 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 12 month follow-up
16. Women who only report "other IE" on bladder diary, and do not report at minimum 1 stress and 1 urge IE/3 days
17. Diagnosis of and/or history of bladder pain or chronic pelvic pain
18. Women who had intravesical Botox injection within the past 12 months
Minimum Eligible Age

21 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role collaborator

University of New Mexico

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role collaborator

Kaiser Permanente

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

RTI International

OTHER

Sponsor Role collaborator

NICHD Pelvic Floor Disorders Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vivian W. Sung

Role: PRINCIPAL_INVESTIGATOR

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

Dennis Wallace

Role: PRINCIPAL_INVESTIGATOR

RTI International

Locations

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University of Alabama at Birmingham, Department of Obstetrics and Gynecology

Birmingham, Alabama, United States

Site Status

Kaiser Permanente -- Downey

Downey, California, United States

Site Status

University of California at San Diego, UCSD Women's Pelvic Medicine Center

La Jolla, California, United States

Site Status

Kaiser Permanente -- San Diego

San Diego, California, United States

Site Status

University of New Mexico Health Sciences Center, Department of Obstetrics and Gynecology

Albuquerque, New Mexico, United States

Site Status

Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery

Durham, North Carolina, United States

Site Status

Cleveland Clinic, Department OB/GYN

Cleveland, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Magee-Womens Hospital, Department of Obstetrics and Gynecology

Pittsburgh, Pennsylvania, United States

Site Status

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

Providence, Rhode Island, United States

Site Status

Countries

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United States

References

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Richter HE, Carnes MU, Komesu YM, Lukacz ES, Arya L, Bradley M, Rogers RG, Sung VW, Siddiqui NY, Carper B, Mazloomdoost D, Dinwiddie D, Gantz MG; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Association between the urogenital microbiome and surgical treatment response in women undergoing midurethral sling operation for mixed urinary incontinence. Am J Obstet Gynecol. 2022 Jan;226(1):93.e1-93.e15. doi: 10.1016/j.ajog.2021.07.008. Epub 2021 Jul 21.

Reference Type DERIVED
PMID: 34297969 (View on PubMed)

Sung VW, Richter HE, Moalli P, Weidner AC, Nguyen JN, Smith AL, Dunivan G, Ridgeway B, Borello-France D, Newman DK, Mazloomdoost D, Carper B, Gantz MG; NICHD Pelvic Floor Disorders Network. Characteristics Associated With Treatment Failure 1 Year After Midurethral Sling in Women With Mixed Urinary Incontinence. Obstet Gynecol. 2021 Aug 1;138(2):199-207. doi: 10.1097/AOG.0000000000004444.

Reference Type DERIVED
PMID: 34237755 (View on PubMed)

Sung VW, Richter HE, Moalli P, Weidner AC, Nguyen JN, Smith AL, Dunivan G, Ridgeway B, Borello-France D, Newman DK, Mazloomdoost D, Carper B, Gantz MG; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network*. Characteristics Associated With Treatment Failure 1 Year After Midurethral Sling in Women With Mixed Urinary Incontinence. Obstet Gynecol. 2020 Sep;136(3):482-491. doi: 10.1097/AOG.0000000000003989.

Reference Type DERIVED
PMID: 32769647 (View on PubMed)

Sung VW, Borello-France D, Newman DK, Richter HE, Lukacz ES, Moalli P, Weidner AC, Smith AL, Dunivan G, Ridgeway B, Nguyen JN, Mazloomdoost D, Carper B, Gantz MG; NICHD Pelvic Floor Disorders Network. Effect of Behavioral and Pelvic Floor Muscle Therapy Combined With Surgery vs Surgery Alone on Incontinence Symptoms Among Women With Mixed Urinary Incontinence: The ESTEEM Randomized Clinical Trial. JAMA. 2019 Sep 17;322(11):1066-1076. doi: 10.1001/jama.2019.12467.

Reference Type DERIVED
PMID: 31529007 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U10HD041261

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD069013

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD054215

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD041267

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD054214

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD069025

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD069010

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD041263

Identifier Type: NIH

Identifier Source: secondary_id

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U01HD069031

Identifier Type: NIH

Identifier Source: secondary_id

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PFDN-26P01

Identifier Type: -

Identifier Source: org_study_id

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