Combined Treatment for Mixed Incontinence (ESTEEM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by NICHD Pelvic Floor Disorders Network
Sponsor:
Collaborators:
Women and Infants Hospital of Rhode Island
The Cleveland Clinic
Duke University
University of Alabama at Birmingham
University of New Mexico
University of Pennsylvania
University of Pittsburgh
University of California, San Diego
Kaiser Permanente
RTI International
Information provided by (Responsible Party):
dwallace, RTI International
ClinicalTrials.gov Identifier:
NCT01959347
First received: October 8, 2013
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Mixed Urinary Incontinence
Procedure: Miduretheral Sling
Other: Miduretheral Sling combined with peri-operative behavioral/pelvic floor therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Caregiver)
Primary Purpose: Treatment
Official Title: Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence (ESTEEM)

Resource links provided by NLM:


Further study details as provided by NICHD Pelvic Floor Disorders Network:

Primary Outcome Measures:
  • Severity of MUI symptoms [ Time Frame: 3, 6, and 12 month visits ] [ Designated as safety issue: No ]
    Change from baseline in severity of MUI symptoms at 1 year following MUS measured using the Urogenital Distress Inventory (UDI).


Secondary Outcome Measures:
  • OAB symptom outcomes [ Time Frame: 3, 6, 12 month visits ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Secondary urinary outcomes [ Time Frame: 3, 6, and 12 month visit ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To determine the cost effectiveness of combined MUS and peri-operative BPTx compared to MUS alone for the treatment of MUI symptoms


Estimated Enrollment: 472
Study Start Date: October 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Miduretheral Sling (Control)
Miduretheral Sling (Control)
Procedure: Miduretheral Sling
Other Name: MUS
Experimental: MUS+BPTx
Miduretheral Sling combined with peri-operative behavioral/pelvic floor therapy
Other: Miduretheral Sling combined with peri-operative behavioral/pelvic floor therapy
Other Name: MUS + BPTx

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01959347

Locations
United States, Alabama
University of Alabama at Birmingham, Department of Obstetrics and Gynecology Recruiting
Birmingham, Alabama, United States, 35249-7333
Contact: Velria Willis, RN, BSN, CCRC    205-975-8522    vwillis@uabmc.edu   
Principal Investigator: Holly E. Richter, PhD, MD         
United States, California
Kaiser Permanente -- Bellflower Recruiting
Downey, California, United States, 90242
Contact: Mercedes Cardona    562-657-4464    Mercedes.X.Cardona@kp.org   
Principal Investigator: John N Nguyen, MD         
University of California at San Diego, UCSD Women's Pelvic Medicine Center Recruiting
La Jolla, California, United States, 92037-0974
Contact: Joann Columbo    858-657-6827    jcolumbo@ucsd.edu   
Principal Investigator: Emily Lukacz, MD         
Kaiser Permanente -- San Diego Recruiting
San Diego, California, United States, 92110
Contact: Gisselle Zazueta-Damian    619-221-6274    Gisselle.Zazueta-Damian@kp.org   
Principal Investigator: Shawn A. Menefee, MD         
United States, New Mexico
University of New Mexico Health Sciences Center, Department of Obstetrics and Gynecology Recruiting
Albuquerque, New Mexico, United States, 87131-0001
Contact: Susan Lee    505-272-6826    srlee@salud.unm.edu   
Principal Investigator: Gena Dunivan, MD         
United States, North Carolina
Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery Recruiting
Durham, North Carolina, United States, 27707
Contact: Shantae Mclean    919-401-1018    shantae.mclean@dm.duke.edu   
Principal Investigator: Alison Weidner, MD         
United States, Ohio
Cleveland Clinic, Department OB/GYN Recruiting
Cleveland, Ohio, United States, 44195
Contact: Ly Pung, RN, BSN    216-445-5505    pungl@ccf.org   
Principal Investigator: Matthew Barber, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michelle Kingless    215-615-6569    kingleem@uphs.upenn.edu   
Principal Investigator: Ariana Smith, MD         
Principal Investigator: Diane Newman, PhD         
Magee-Womens Hospital, Department of Obstetrics and Gynecology Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Judy Gruss, RN    412-641-5388    grusja@mail.magee.edu   
Principal Investigator: Pam Moalli, MD         
Principal Investigator: Diane Borello- France, PhD         
United States, Rhode Island
Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery Recruiting
Providence, Rhode Island, United States, 02903
Contact: Ann Meers, RN, CCRC    401-276-7869    ameers@wihri.org   
Principal Investigator: Vivian Sung, MD         
Sponsors and Collaborators
NICHD Pelvic Floor Disorders Network
Women and Infants Hospital of Rhode Island
The Cleveland Clinic
Duke University
University of Alabama at Birmingham
University of New Mexico
University of Pennsylvania
University of Pittsburgh
University of California, San Diego
Kaiser Permanente
RTI International
Investigators
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
  More Information

No publications provided

Responsible Party: dwallace, Project Director, RTI International
ClinicalTrials.gov Identifier: NCT01959347     History of Changes
Other Study ID Numbers: PFDN-26P01, U10HD041261, U10HD069013, U10HD054215, U10HD041267, U10HD054214, U10HD069025, U10HD069010, U10HD041263, U01HD069031
Study First Received: October 8, 2013
Last Updated: April 17, 2014
Health Authority: United States: Federal Government

Keywords provided by NICHD Pelvic Floor Disorders Network:
Mixed urinary incontinence, midurethral sling, pelvic floor therapy

Additional relevant MeSH terms:
Urinary Incontinence
Urination Disorders
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on September 16, 2014