Anticholinergic vs. Botox Comparison Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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.

Official Title
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Efficacy and Impact of Botulinum Toxin A Versus Anticholinergic Therapy for the Treatment of Bothersome Urge Urinary Incontinence

Conditions
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Urge Urinary Incontinence, Overactive Bladder

Intervention / Treatment
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* Drug: Botulinum toxin A (Botox A®)
* Drug: Solifenacin 5mg
* Drug: Solifenacin 10mg
* Drug: Trospium chloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botox A<br>A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets | Drug: Botulinum toxin A (Botox A®)<br>* 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.<br>* Other names: (Botox A®);|
| Active Comparator: Standardized Anticholinergic Regimen<br>A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium chloride XR 60mg, as well as a single intradetrusor injection of saline (placebo). All subjects will begin on solifenacin 5 mg for 2 mo. If a subject's symptoms are not adequately controlled at 2 mo, she will be escalated to solifenacin 10mg, and similarly at 4 mo to trospium XR 60mg. If a subject's symptoms are adequately controlled on solifenacin 5 mg, she may continue that study medication for the entirety of the study (6 mo). Additionally, if a subject is dose-escalated to solifenacin 10mg at study mo 2 or 4, and her symptoms are adequately controlled, she may continue the solifenacin 10mg dose for the remainder of the study. | Drug: Solifenacin 5mg<br>* Oral Solifenacin 5mg once a day for up to 6 months<br>* Other names: Vesicare;Drug: Solifenacin 10mg<br>* Oral Solifenacin 10mg once a day for up to 4 months<br>* Other names: Vesicare;Drug: Trospium chloride<br>* Oral Trospium chloride XR 60mg once a day for up to 2 months<br>* Other names: Sanctura;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urge Urinary Incontinence (UUI) Episodes | Change from baseline in mean number of UUI episodes over 6 month double-blind period. | Baseline through 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Score on OABq-SF | Values for the Overactive Bladder Questionnaire Short Form (OABq-SF) are changes from baseline in the adjusted mean scores for months 1 to 6. Scores on the OABq-SF range from 0 to 100, with higher scores on the symptom-severity scale indicating greater severity of symptoms and higher scores on the quality-of-life scale indicating better quality of life. Data were available for 123 participants in the Standardized Anticholinergic Regimen group and 119 in the Botox A A group. | Baseline through 6 months | 
| Efficacy | Efficacy outcomes assessed reduction and resolution of incontinence, including urgency urinary incontinence (UUI). | 6 months | 
| Change in PFDI-SF and PFIQ-SF Total Scores | Values for Pelvic Floor Distress Inventory Short Form (PFDI-SF) are changes from baseline in the adjusted mean scores for months 3 to 6. Scores on the PFDI-SF range from 0 to 300, with higher scores indicating more symptoms and more bothersome symptoms. Values for the Pelvic Floor Impact Questionnaire Short Form (PFIQ-SF) are changes from baseline in the adjusted mean scores for months 3 to 6. Scores on the PFIQ-SF range from 0 to 300, with higher scores indicating a more negative effect on activities, relationships, and feelings. | Baseline through 6 months | 
| Patient Global Impression of Improvement | The Patient Global Impression of Improvement (PGI-I) is a patient-reported measure of perceived improvement with treatment, as assessed on a scale of 1 (very much better) to 7 (very much worse). Included here are participants who had adequate improvement, defined as a rating of 1 or 2 (much better). | 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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incontinence, overactive bladder, botox, anticholinergic