Trial of NASHA Dx Urethral Bulking System

1. 1. Female, ≥ 18 years of age
2. All women of childbearing potential must have a negative urine pregnancy test result documented prior to inclusion into the trial at Screening.
3. SUI or stress predominant mixed urinary incontinence due to intrinsic sphincter deficiency (ISD) for at least 6 months
4. Failed conservative therapy for stress urinary incontinence
5. Documentation of at least 3 stress urinary incontinence episodes measured over 3 days
6. Baseline 24-hr. pad weight test ≥ 5 g
7. Intrinsic sphincter deficiency stress urinary incontinence defined as a urodynamic assessment in the past 6 months with Valsalva leak-point pressure (VLPP) \< 60 cm H2O and/or a maximal urethral closure pressure (MUCP) 20 cm H2O
8. Clinical laboratory values such as white blood cell count, hemoglobin, AST/ALT, Creatinine, Bilirubin, blood glucose are within normal limits, or if abnormal, considered and documented as not clinically significant by the investigator
9. Cleared for surgery by anesthesiologist preoperatively
10. Life expectancy of more than 2 years
11. Been informed of, and be able to perform, the study treatments and procedures, and signed an informed consent form.
12. Provided authorization to use and disclose information for research purposes [HIPAA (Health Insurance Portability and Accountability Act of 1996; US sites) or country-specific requirement]

Exclusion Criteria:

1. 1. Urgency Predominant Mixed urinary incontinence, confirmed by 3-day bladder diary. (greater than 50% of incontinence episodes due to urge or less than 50% of incontinence episodes due to stress).
2. Negative cough test or lack of leakage with valsalva maneuver on physical exam
3. Historical Detrusor overactivity as determined by urodynamic assessment within the past year
4. Significant urethral hypermobility (e.g. vaginal swab > 30° from horizontal bladder neck)
5. History of urethral bulking, artificial urinary sphincters and previous urethral surgery for incontinence or non-incontinence related indications (eg. fistulas or diverticula) are not permitted
6. Patient may not have undergone a Mid-Urethral Sling (MUS), retropubic colpo or pubovaginal sling less than 6 months from screening
7. Polyuria (≥ 3 L/24 hrs.)
8. Three or more culture proven bacterial UTIs in the last 12 months or 2 culture proven bacterial UTIs in the last 6 months
9. Current urogenital infection: urethritis, cystitis, urinary tract infection or vaginitis
10. Unevaluated hematuria
11. No prolapse through the introitus at screening visit
12. Body mass index (BMI) > 35 kg/m2
13. Currently taking or has taken within 4 weeks prior to the screening/baseline visit, pharmacological treatment for Overactive Bladder (OAB) (including but not limited to anti-cholinergics or beta adrenergics)
14. Allergy to hyaluronic acid-based products or dextran or history of severe allergies or anaphylaxis including hypersensitivity to local anesthetics such as lidocaine or antibiotics used for treating urinary tract infections
15. Active autoimmune diseases (e.g., connective tissue diseases) that could affect or confound treatment outcome
16. Systemic corticosteroids - currently taking, or has taken, within 3 months prior to the initial treatment visit
17. Currently has cancer or has a history of cancer within the past 5 years. Subjects with a history of skin cancer with no evidence of skin malignancy for less than 2 years, will be excluded. Note: basal cell carcinoma is not an exclusion criterion
18. Any unstable or severe cardio-vascular disease
19. Uncontrolled diabetes defined as HbA1c greater than 8% within the prior 6 months or at screening. Note: Patients with suspected or known diabetes mellitus type II who lack an HbA1c result within the past 6 months will have a random glucose test at screening and a HbA1c test at screening. Patients with blood glucose >180 mg/dL will be excluded or HbA1c of 8% or greater will be excluded
20. Active herpes genitalis (lesion, prodrome, symptoms)
21. Currently participating in any other clinical trial or has participated in another clinical trial within 3 months prior to the screening/baseline visit, where the outcome measures may overlap.
22. History of drug/alcohol abuse, mental dysfunction health condition, or other factors limiting her ability to cooperate fully
23. Pregnant, lactating, or not practicing adequate contraception (refer to inclusion criteria), was intending to become pregnant, or to lactate for the duration of this study (approximately 12 months)
24. Not physically able to perform study procedures
25. Bladder dysfunction in the setting of known neurologic disease that negatively impacts bladder function (including but not limited to stroke, multiple sclerosis, and Parkinson's disease) or known neurologic pathology that in the opinion of the investigator contributes to bladder dysfunction
26. Post Void Residual (PVR) > 150 ml on at least 2 occasions
27. Uncontrolled bleeding disorders
28. Impassable urethral strictures
29. Vaginal delivery or Cesarean section within 3 months prior to the screening/baseline visit
30. Any other condition, which, in the opinion of the investigator, would make the subject not a suitable candidate for the study