ABC: Anticholinergic vs. Botox Comparison Study

• Sponsor: NICHD Pelvic Floor Disorders Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT01166438
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 249
• Locations: 11
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 22.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Urge Urinary Incontinence; Overactive Bladder	Drug: Botulinum toxin A (Botox A®); Drug: Solifenacin 5mg; Drug: Solifenacin 10mg; Drug: Trospium chloride	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 249 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Impact of Botulinum Toxin A Versus Anticholinergic Therapy for the Treatment of Bothersome Urge Urinary Incontinence
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Botox A A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets	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.; Other Names: (Botox A®)
Active Comparator: Standardized Anticholinergic Regimen 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; Oral Solifenacin 5mg once a day for up to 6 months; Other Names: Vesicare ; Drug: Solifenacin 10mg; Oral Solifenacin 10mg once a day for up to 4 months; Other Names: Vesicare ; Drug: Trospium chloride; Oral Trospium chloride XR 60mg once a day for up to 2 months; Other Names: Sanctura

Outcome Measures

Primary Outcome Measures

1. Change in Urge Urinary Incontinence (UUI) Episodes [Baseline through 6 months]

   Change from baseline in mean number of UUI episodes over 6 month double-blind period.

Secondary Outcome Measures

1. Change From Baseline in Score on OABq-SF [Baseline through 6 months]

   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.

2. Efficacy [6 months]

   Efficacy outcomes assessed reduction and resolution of incontinence, including urgency urinary incontinence (UUI).

3. Change in PFDI-SF and PFIQ-SF Total Scores [Baseline through 6 months]

   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.

4. Patient Global Impression of Improvement [3 and 6 months]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	USCD Medical Center	La Jolla	California	United States	92037
3	Kaiser Permanente	San Diego	California	United States	92037
4	Loyola University Medical Center	Maywood	Illinois	United States	60153
5	Oakwood Hospital	Dearborn	Michigan	United States	48124
6	Beaumont Hospital	Royal Oak	Michigan	United States	48073
7	Duke University	Durham	North Carolina	United States	27710
8	Cleveland Clinic	Cleveland	Ohio	United States	44195
9	Magee-Women's Hospital	Pittsburgh	Pennsylvania	United States	15213
10	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
11	University of Utah	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

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

Investigators

• Study Chair: Anthony Visco, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Pelvic Floor Disorders Network
• ABC Study Information

Publications

None provided.

• Responsible Party: NICHD Pelvic Floor Disorders Network
• ClinicalTrials.gov Identifier: NCT01166438
• Other Study ID Numbers: PFDN 17; 2U01HD041249; 2U10HD041250; 2U10HD041261; 2U10HD041267; 1U10HD054136; 1U10HD054214; 1U10HD054215; 1U10HD054241
• First Posted: Jul 21, 2010
• Last Update Posted: May 2, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by NICHD Pelvic Floor Disorders Network: incontinence; overactive bladder; botox; anticholinergic
• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Solifenacin Succinate; Trospium chloride; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 mon
Period Title: Double-blind Phase: 1st 6 Months
STARTED	122	127
Treated	121	126
COMPLETED	113	118
NOT COMPLETED	9	9
Period Title: Double-blind Phase: 1st 6 Months
STARTED	85	89
COMPLETED	51	33
NOT COMPLETED	34	56

Baseline Characteristics

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen	Total
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 mon	Total of all reporting groups
Overall Participants	121	126	247
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.3 (10.8)	56.7 (11.6)	57.9 (11.3)
Sex: Female, Male (Count of Participants)
Female	121 100%	126 100%	247 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 18.2%	22 17.5%	44 17.8%
Not Hispanic or Latino	99 81.8%	104 82.5%	203 82.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	1 0.8%	2 0.8%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 0.8%	0 0%	1 0.4%
Black or African American	18 14.9%	23 18.3%	41 16.6%
White	96 79.3%	98 77.8%	194 78.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 4.1%	4 3.2%	9 3.6%
Marital Status (Count of Participants)
Married or living as married	58 47.9%	57 45.2%	115 46.6%
Divorced, separated, or widowed	44 36.4%	48 38.1%	92 37.2%
Single, never married	15 12.4%	16 12.7%	31 12.6%
Other	0 0%	1 0.8%	1 0.4%
Not reported	4 3.3%	4 3.2%	8 3.2%
Educational level at least some college (Count of Participants)
Count of Participants [Participants]	86 71.1%	90 71.4%	176 71.3%
Type of health insurance (Count of Participants)
Private only	61 50.4%	60 47.6%	121 49%
Medicare or Medicaid only	10 8.3%	16 12.7%	26 10.5%
Other only	28 23.1%	34 27%	62 25.1%
Combination of several types	21 17.4%	16 12.7%	37 15%
Not reported	1 0.8%	0 0%	1 0.4%
Smoking status (Count of Participants)
Never smoked	66 54.5%	74 58.7%	140 56.7%
Previous smoker	39 32.2%	40 31.7%	79 32%
Current smoker	15 12.4%	12 9.5%	27 10.9%
Not reported	1 0.8%	0 0%	1 0.4%
Menopausal status (Count of Participants)
Premenopausal	15 12.4%	22 17.5%	37 15%
Postmenopausal	102 84.3%	92 73%	194 78.5%
Not sure	4 3.3%	12 9.5%	16 6.5%
No prior anticholinergic therapy (Count of Participants)
Count of Participants [Participants]	48 39.7%	54 42.9%	102 41.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 mon
Measure Participants	119	122
1 Month	-3.13 (0.2851)	-3.15 (0.2761)
2 Months	-3.32 (0.2854)	-3.25 (0.2762)
3 Months	-3.22 (0.2854)	-3.55 (0.278)
4 Months	-3.36 (0.2857)	-3.40 (0.2766)
5 Months	-3.42 (0.2881)	-3.49 (0.2777)
6 Months	-3.27 (0.2864)	-3.33 (0.2775)

2. Secondary Outcome

Title	Change From Baseline in Score on OABq-SF
Description	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.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 mon
Measure Participants	119	123
OABq-SF Symptom Severity Score	-44.08 (2.54)	-44.55 (2.44)
OABq-SF Quality of Life Score	37.13 (2.578)	37.05 (2.479)

3. Secondary Outcome

Title	Efficacy
Description	Efficacy outcomes assessed reduction and resolution of incontinence, including urgency urinary incontinence (UUI).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Efficacy outcomes were assessed in the modified intention-to-treat population, which included all participants who underwent randomization and received a study medication and who had a baseline measure and at least one follow-up measure for the outcome. Proportions were based on data from participants who returned at least four follow-up diaries.

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 mon
Measure Participants	112	119
Complete resolution of UUI	30 24.8%	16 12.7%
Complete resolution of all incontinence	26 21.5%	13 10.3%
>75% reduction in UUI episodes	61 50.4%	48 38.1%

4. Secondary Outcome

Title	Change in PFDI-SF and PFIQ-SF Total Scores
Description	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.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

Data were available for 111 participants in the Standardized Anticholinergic Regimen group and 102 in the Botox A group.

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 mon
Measure Participants	102	111
Change from baseline in PFDI-SF total score	-48.20 (5.56)	-43.69 (5.34)
Change from baseline in PFIQ-SF total score	-33.85 (6.313)	-32.82 (6.065)

5. Secondary Outcome

Title	Patient Global Impression of Improvement
Description	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).
Time Frame	3 and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Botox A	Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.	A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium 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. 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 XR 60mg once a day for up to 2 months
Measure Participants	111	116
Month 3	61 50.4%	59 46.8%
Month 6	60 49.6%	67 53.2%

Adverse Events

Arm/Group Title	Botox A		Standardized Anticholinergic Regimen
Arm/Group Description	A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets 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.		A standardized 3-step anticholinergic regimen of daily oral solifenacin 5mg, solifenacin 10mg, and/or trospium XR 60mg, as well as a single intradetrusor injection of saline (placebo). All subjects will begin on solifenacin 5 mg for 2 mo. Dose escalation or drug change will be based exclusively on the result of the Patient Global Symptom Control Rating. 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.
All Cause Mortality
	Botox A		Standardized Anticholinergic Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Botox A		Standardized Anticholinergic Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/121 (4.1%)		7/126 (5.6%)
Cardiac disorders
Cardiac septal hypertrophy	0/121 (0%)		1/126 (0.8%)
Myocardial infarction	0/121 (0%)		1/126 (0.8%)
Gastrointestinal disorders
Ileus	0/121 (0%)		1/126 (0.8%)
General disorders
Chest Pain	0/121 (0%)		1/126 (0.8%)
Hepatobiliary disorders
Cholelithiasis	0/121 (0%)		1/126 (0.8%)
Infections and infestations
Appendicitis	0/121 (0%)		1/126 (0.8%)
Upper respiratory tract infection	1/121 (0.8%)		0/126 (0%)
Injury, poisoning and procedural complications
Head injury	1/121 (0.8%)		0/126 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/121 (0.8%)		0/126 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma	0/121 (0%)		1/126 (0.8%)
Nervous system disorders
Convulsion	1/121 (0.8%)		0/126 (0%)
Renal and urinary disorders
Haematuria	1/121 (0.8%)		0/126 (0%)
Other (Not Including Serious) Adverse Events
	Botox A		Standardized Anticholinergic Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/121 (79.3%)		97/126 (77%)
Eye disorders
Dry eye	32/121 (26.4%)		31/126 (24.6%)
Any Eye Disorders	34/121 (28.1%)		31/126 (24.6%)
Gastrointestinal disorders
Constipation	31/121 (25.6%)		37/126 (29.4%)
Diarrhea	21/121 (17.4%)		15/126 (11.9%)
Dry mouth	44/121 (36.4%)		64/126 (50.8%)
Nausea	6/121 (5%)		5/126 (4%)
Any Gastrointestinal Disorders	63/121 (52.1%)		74/126 (58.7%)
General disorders
Chills	12/121 (9.9%)		12/126 (9.5%)
Influenza-like illness	9/121 (7.4%)		7/126 (5.6%)
Injection site pain	34/121 (28.1%)		36/126 (28.6%)
Pyrexia	8/121 (6.6%)		6/126 (4.8%)
Any General Disorders and Administration Site Conditions	49/121 (40.5%)		41/126 (32.5%)
Immune system disorders
Hypersensitivity	7/121 (5.8%)		1/126 (0.8%)
Any Immune System Disorders	7/121 (5.8%)		1/126 (0.8%)
Infections and infestations
Urinary tract infection	37/121 (30.6%)		19/126 (15.1%)
Any Infections and Infestations	37/121 (30.6%)		20/126 (15.9%)
Musculoskeletal and connective tissue disorders
Flank Pain	8/121 (6.6%)		3/126 (2.4%)
Any Musculoskeletal and Connective Tissue Disorders	11/121 (9.1%)		5/126 (4%)
Renal and urinary disorders
Haematuria	28/121 (23.1%)		23/126 (18.3%)
Urine abnormality	17/121 (14%)		14/126 (11.1%)
Urine odour abnormal	16/121 (13.2%)		10/126 (7.9%)
Any Renal and Urinary Disorders	49/121 (40.5%)		38/126 (30.2%)
Skin and subcutaneous tissue disorders
Rash	8/121 (6.6%)		6/126 (4.8%)
Any Skin and Subcutaneous Tissue Disorders	8/121 (6.6%)		6/126 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.