Anticholinergic vs. Botox Comparison Study

Overactive Bladder Clinical Trial

— ABC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01166438
• Other study ID #: PFDN 17
• Secondary ID: 2U01HD0412492U10
• Status: Completed
• Phase: Phase 3
• Start date: March 2010
• Est. completion date: May 2012

Study information

• Verified date: April 2018
• Source: NICHD Pelvic Floor Disorders Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Enuresis
• Overactive Bladder
• Urge Urinary Incontinence
• Urinary Bladder, Overactive
• Urinary Incontinence
• Urinary Incontinence, Urge

Intervention

Drug:
• Botulinum toxin A (Botox A®)
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.
• Solifenacin 5mg
Oral Solifenacin 5mg once a day for up to 6 months
• Solifenacin 10mg
Oral Solifenacin 10mg once a day for up to 4 months
• Trospium chloride
Oral Trospium chloride XR 60mg once a day for up to 2 months

Locations

Country	Name	City	State
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Oakwood Hospital	Dearborn	Michigan
United States	Duke University	Durham	North Carolina
United States	USCD Medical Center	La Jolla	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Magee-Women's Hospital	Pittsburgh	Pennsylvania
United States	Beaumont Hospital	Royal Oak	Michigan
United States	University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Pelvic Floor Disorders Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Efficacy	Efficacy outcomes assessed reduction and resolution of incontinence, including urgency urinary incontinence (UUI).	6 months
Secondary	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
Secondary	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

External Links

•   ABC Study Information
•   Pelvic Floor Disorders Network