Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (ROSETTA)
Condition: Urinary Incontinence, Urge
MeSH terms: Urinary Incontinence; Urinary Bladder, Overactive; Urinary Incontinence, Urge
Intervention: InterStim® device; Botox® injection
Intervention description: Eligible subjects will complete baseline assessments, be randomized and scheduled for first stage lead placement (FSLP) InterStim®. The criterion for an initial clinical response to InterStim® therapy will be defined as a ≥50% improvement in the mean number of UUIE/day on a minimum 3 day bladder diary, completed during the 7-14 days following the first stage lead placement (FSLP). Subjects with a ≥ 50% improvement mean number of UUIE/day will be eligible to proceed with implantation of the implantable pulse generator (IPG). Subjects will then be followed monthly to determine the response to therapy.; Eligible subjects will complete baseline assessments, be randomized and scheduled for Botox A® injection visit. Subjects who received a Botox A® injection will be assessed for a clinical response, at 1 month from injection, using the same clinical criterion (≥50% improvement in the mean number of UUIE/day on a 3 day bladder diary completed prior to the 1 month visit). Those subjects that experience a clinical response, at one month, will be eligible for a repeat Botox A® injection after 6 months, if they experience degradation of clinical effect, using the PGSC.
Intervention MeSH terms: Botulinum Toxins, Type A
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 386.0
Sex: Female
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Refractory Urinary Urge Incontinence; Botox A®; Interstim® Device

Summary:

      The purpose of this randomized, open-label, active-control trial is to compare the
      effectiveness of intra-detrusor botulinum toxin A (Botox A®, Allergan) versus sacral
      neuromodulation (InterStim®, Medtronic) for the treatment of refractory urge urinary
      incontinence. In addition, the study will evaluate select technical attributes of the
      interventions as well as the effect of these two interventions on other lower urinary tract
      and pelvic floor symptoms.

      Hypothesis: InterStim® therapy will result in a greater reduction in daily urge urinary
      incontinence episodes over the 6-month follow-up period as compared to Botox A® injection.

      A supplemental study investigates whether biological markers including those related to
      inflammation and connective tissue remodeling change following treatments with Botox A® and
      Interstim®.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Non-pregnant adult female at least 21 years old, with no plans to become pregnant
             during the course of the trial) and if of child-bearing potential, with a negative
             pregnancy test, and if sexually active, must be using medically acceptable
             contraception.

          -  6 urge urinary incontinence episodes on a 3-day baseline bladder diary, with these
             urge incontinence episodes representing greater than 50% of the total incontinent
             episodes recorded.

          -  Willing and able to complete all study related items and interviews.

          -  Refractory urinary urge urinary incontinence: defined as (1) Persistent symptoms
             despite at least one or more conservative treatments (e.g. supervised behavioral
             therapy, supervised physical therapy); and (2)Persistent symptoms despite the use of a
             minimum of two anticholinergics, or unable to tolerate medication due to side effects,
             or has a contraindication to taking anticholinergic medication.

          -  Currently not on an anticholinergic or antimuscarinic medication (e.g. oxybutynin,
             tolterodine, and/or fesoterodine) or be willing to stop medication for 3 weeks prior
             to completing baseline bladder diary and expected to remain off medications through
             duration of study.

          -  Demonstrates ability (or have caregiver demonstrate ability) to perform clean
             intermittent self-catheterization.

          -  Grossly neurologically normal on exam and no gross systemic neurologic conditions
             believed to affect urinary function.

          -  Urodynamic assessment within the previous 18 months prior to enrollment or done after
             enrollment, prior to randomization.

        Exclusion Criteria:

          -  Neurologic diseases such as multiple sclerosis, Parkinson Disease, CVA within 6 months
             prior to enrollment, myasthenia gravis, Charcot-Marie-Tooth disease, clinically
             significant peripheral neuropathy, and complete spinal cord injury.

          -  Untreated urinary tract infection (UTI).

          -  Any prior use of either study therapy for treatment of urinary urge incontinence
             (Botox A® or Interstim®).

          -  Current participation in any other conflicting interventional research study.

          -  PVR >150 ml on 2 occasions within 6 months prior to enrollment (If the PVR value was
             obtained by ultrasound and was ≥150 ml, the PVR will be confirmed by catheterization
             which will be the gold standard)

          -  Subjects with knowledge of planned MRIs or diathermy, except those allowable per
             Medtronic guidelines.

          -  Current or prior bladder malignancy.

          -  Surgically altered detrusor muscle, such as augmentation cystoplasty.

          -  Subjects taking aminoglycosides.

          -  Currently pregnant or lactating.

          -  Subjects who are on ambulatory anticoagulant therapy, including aspirin, who are
             unable to discontinue treatment for 24 hours prior to bladder injection and staged
             InterStim® procedure.

          -  Serum creatinine level greater than twice the upper limit of normal within the
             previous year prior to enrollment.

          -  Surgical treatment for stress incontinence (sling, Burch or urethral injection) or
             pelvic organ prolapse recommended or planned at enrollment by study investigator(s).

          -  Prior stress incontinence or prolapsed surgery within the last 6 months prior to
             enrollment.

          -  Allergy to lidocaine or bupivacaine.

          -  Prior pelvic radiation.

          -  Uninvestigated hematuria.

          -  Greater than or equal to Stage III vaginal prolapse.

          -  Known allergy to Botox A®.

          -  Use of a vaginal pessary.