Status:Active, not recruiting
Keywords:Urge Incontinence , Overactive Bladder , Urinary Incontinence , BOTOX
Specialty:Urogyn and Pelvic Reconstructive Surgery
This study is a 6-month double-blind randomized trial comparing intra-detrusor botulinum toxin A (Botox A®) and anticholinergic therapy in women without neurologic disease with urge incontinence. All subjects will receive active drug and all subjects will receive placebo (see below). Subjects will be followed up to an additional six months off study drug to determine duration of treatment effect.
The primary aim is to compare the change in urge incontinence episodes over 6 months between women receiving a single intra-detrusor injection of 100 unit of botulinum toxin A (Botox A®) plus daily oral placebo tablets versus women receiving a single intra-detrusor injection of saline plus daily anticholinergic therapy. 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.
The secondary aims are:
1) To compare efficacy of both treatments arms in reducing urgency and urge incontinence (occurrence and bother).
2) To assess duration of effect (time with adequate control of urinary leakage) of each treatment arm (single injection of 100U botulinum toxin A or 6 months of anticholinergic therapy)
3) To compare the change from baseline in pelvic floor-specific, sexual and overall quality of life measures and treatment satisfaction between botulinum toxin A and anticholinergic medication
4) To compare safety and tolerability (urinary retention requiring catheterization, incomplete bladder emptying, dry mouth, dry eyes, constipation) between botulinum toxin A and anticholinergic medication
5) To compare compliance with placebo versus active pills
6) To compare cost-effectiveness between botulinum toxin A and anticholinergics management of urge incontinence
7) To describe outcomes (symptom control, urinary tract infections) using a standardized threshold and regimen for instituting clean intermittent self-catheterization
8) To describe clinical and urodynamic parameters (measured at baseline) that are associated with effectiveness and side effects including new onset voiding dysfunction and partial urinary retention in both treatment groups
9) To describe the proportion of subjects who have adequate symptom control with the active standardized anticholinergic regimen
1) Subject has signed informed consent
2) Females at least 21 years of age
3) 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.
4) Urge predominant (urge >50% of total incontinent episodes) urinary incontinence based on self-reported characterization of incontinent episodes on diary.
5) Demonstrated ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization in the event that this would be required.
6) 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.
7) Subject has undergone 3-week washout period if subject were on anticholinergic therapy prior to starting the baseline voiding diary for eligibility.
8) Subject is able to complete all study related items and interviews.
1) Any previous therapy with trospium chloride, solifenacin, or darifenacin
2) Failed three or more anticholinergic drugs.
Note: We define drugs based on the active compound of the particular medication. Any and all formulations of a particular active compound will be considered as a single drug trial. Specifically, any and all formulations of oxybutynin will be considered a single attempt with this active compound. Any use of tolterodine or fesoterodine will be considered a single drug trial of fesoterodine.
3) Contraindication to anticholinergic therapy, specifically with solifenacin or trospium.
4) Current symptomatic urinary tract infection that has not resolved prior to randomization.
5) Uncontrolled narrow-angle glaucoma
6) Gastric retention
7) Baseline need for intermittent self catheterization
8) PVR >150ml on 2 occasions with void(s) of greater than 150ml
9) Surgical treatment for stress incontinence (sling, Burch or urethral injection) or pelvic organ prolapse recommended or planned at enrollment by study investigator(s).
10) Any prior intra-detrusor botulinum toxin A injections
11) Previous or currently implanted neuromodulation (sacral or tibial).
12) Surgically altered detrusor muscle, such as augmentation cystoplasty.
13) Known allergy to botulinum toxin A.
14) Women with known neurologic disease believed to potentially affect urinary function (Multiple sclerosis, spinal cord injuries, myasthenia gravis, Charcot-Marie-Tooth disease).
15) Known allergy to lidocaine.
16) Currently pregnant or lactating patients or patients planning pregnancy within the next year.
17) 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.
18) Cystoscopic findings that preclude injection, in the opinion of the investigator.
19) Current or prior bladder malignancy.
20) In the opinion of the investigator, inability to understand diary instructions and complete 3-day voiding diary.
21) Subjects who are on anticoagulant therapy,excluding aspirin
22) Subject has been previously diagnosed with interstitial cystitis or chronic pelvic pain syndrome.
23) Subjects with hematuria who have not undergone a clinically appropriate evaluation.
24) Subjects taking aminoglycosides at the time of injection.
25) Serum creatinine level greater than twice the upper limit of normal within the previous year.
26) Two or more hospitalizations for medical conditions in the previous year.
27) Plans to move out of area in the next 6 months.