Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (ROSETTA)

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: Female

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®.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NICHD Pelvic Floor Disorders Network
• Collaborators: Brown University; Duke University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Oregon Health and Science University; RTI International; The Cleveland Clinic; University of Alabama at Birmingham; University of California, San Diego; University of New Mexico; University of Pennsylvania; University of Pittsburgh
• Treatments: abobotulinumtoxinA; Botulinum Toxins; Botulinum Toxins, Type A; incobotulinumtoxinA; onabotulinumtoxinA

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.