Anticholinergic vs. Botox Comparison Study
Condition: Urge Urinary Incontinence; Overactive Bladder
MeSH terms: Urinary Incontinence; Enuresis; Urinary Bladder, Overactive; Urinary Incontinence, Urge
Intervention: Botulinum toxin A (Botox A®); Solifenacin 5mg; Solifenacin 10mg; Trospium chloride
Intervention description: A single intradetrusor injection of 100U botulinum toxin A in 10 mL plus 0.1 mL of indigo carmine administered during cytoscopy. Between 100 and 200ml of saline is instilled into the bladder prior to injection to allow adequate visualization of the entire bladder urothelium. The treating physician will inject a total of 10.1 mL of the masked substance into approximately 15 to 20 different detrusor muscle sites under direct visualization using disposable needles. Injections will be spread out to equally cover the posterior bladder wall and dome, but spare the bladder trigone and ureteral orifices.; Oral Solifenacin 5mg once a day for up to 6 months; Oral Solifenacin 10mg once a day for up to 4 months; Oral Trospium chloride XR 60mg once a day for up to 2 months
Intervention MeSH terms: Solifenacin Succinate; Trospium chloride; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 249.0
Sex: Female
Minimum age: 21 Years
Healthy volunteers: No
Keywords: incontinence; overactive bladder; botox; anticholinergic

Summary:

      Urinary incontinence is a prevalent condition that markedly impacts quality of life and
      disproportionately affects women. Overactive Bladder syndrome (OAB) is defined as symptoms of
      urgency and frequency with urge urinary incontinence (OAB-wet) and without urge incontinence
      (OAB-dry). Conservative first line treatments for urge incontinence combined with other OAB
      symptoms (OAB-wet) include behavioral therapy, pelvic floor training +/- biofeedback, or the
      use of anticholinergic medications. These treatment modalities may not result in total
      continence and often drug therapy is discontinued because of lack of efficacy, side effects
      and cost or because of not wanting to take a pill. Behavioral therapy and pelvic muscle
      exercises require consistent, active intervention by the patient which is often not
      sustained. Thus, the objective of the Anticholinergic vs Botox Comparison Study (ABC) is to
      determine whether a single intra-detrusor injection of botulinum toxin A (Botox A®) is more
      effective than a standardized regimen of oral anticholinergics in reducing urge urinary
      incontinence. The null hypothesis is that there is no difference in the change from baseline
      in average number of urge urinary incontinence episodes over 6 months between groups.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has signed informed consent.

          -  Females at least 21 years of age

          -  Five or more urge urinary incontinence episodes on a three-day voiding diary. Urge
             incontinence episodes will be determined based on voiding diary and subject indication
             of coincident urge symptoms, allowing self-characterization of incontinence type.

          -  Urge predominant (urge >50% of total incontinent episodes) urinary incontinence based
             on self-reported characterization of incontinent episodes on diary.

          -  Demonstrated ability (or have caregiver demonstrate ability) to perform clean
             intermittent self-catheterization in the event that this would be required.

          -  Request for treatment for urge urinary incontinence. The patient may have tried other
             non-pharmacologic treatments for urge incontinence, such as supervised behavioral
             therapy, supervised physical therapy, unsupervised physical therapy, supervised
             biofeedback, and transvaginal electrical stimulation.

          -  Subject has undergone 3-week washout period if subject were on anticholinergic therapy
             prior to enrollment.

          -  Subject is able to complete all study related items and interviews.

        Exclusion Criteria:

          -  Any previous therapy with trospium chloride, solifenacin, or darifenacin

          -  Failed three or more anticholinergic drugs.

          -  Contraindication to anticholinergic therapy, specifically with solifenacin or
             trospium.

          -  Current symptomatic urinary tract infection that has not resolved prior to
             randomization.

          -  Uncontrolled narrow-angle glaucoma

          -  Gastric retention

          -  Baseline need for intermittent self catheterization

          -  PVR >150ml on 2 occasions with void(s) of greater than 150ml

          -  Surgical treatment for stress incontinence (sling, Burch or urethral injection) or
             pelvic organ prolapse recommended or planned at enrollment by study investigator(s).

          -  Any prior intra-detrusor botulinum toxin A injections

          -  Previous or currently implanted neuromodulation (sacral or tibial).

          -  Surgically altered detrusor muscle, such as augmentation cystoplasty.

          -  Known allergy to botulinum toxin A.

          -  Women with known neurologic disease believed to potentially affect urinary function
             (Multiple sclerosis, spinal cord injuries, myasthenia gravis, Charcot-Marie-Tooth
             disease).

          -  Known allergy to lidocaine.

          -  Currently pregnant or lactating patients or patients planning pregnancy within the
             next year.

          -  Sexually active premenopausal women with a uterus who have either not had a tubal
             ligation or are not on a medically approved form of contraception for at least 3
             months prior to and throughout the duration of the study.

          -  Cystoscopic findings that preclude injection, in the opinion of the investigator.

          -  Current or prior bladder malignancy.

          -  In the opinion of the investigator, inability to understand diary instructions and
             complete 3-day voiding diary.

          -  Subjects who are on anticoagulant therapy,excluding aspirin

          -  Subject has been previously diagnosed with interstitial cystitis or chronic pelvic
             pain syndrome.

          -  Subjects with hematuria who have not undergone a clinically appropriate evaluation.

          -  Subjects taking aminoglycosides at the time of injection.

          -  Serum creatinine level greater than twice the upper limit of normal within the
             previous year.

          -  Two or more hospitalizations for medical conditions in the previous year.

          -  Plans to move out of area in the next 6 months.