Combined Treatment for Mixed Incontinence

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.

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