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Anticholinergic vs. Botox Comparison Study (ABC)

Primary Purpose

Urge Urinary Incontinence, Overactive Bladder

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Botulinum toxin A (Botox A®)
Solifenacin 5mg
Solifenacin 10mg
Trospium chloride
Sponsored by
NICHD Pelvic Floor Disorders Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urge Urinary Incontinence focused on measuring incontinence, overactive bladder, botox, anticholinergic

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • The University of Alabama at Birmingham
  • USCD Medical Center
  • Kaiser Permanente
  • Loyola University Medical Center
  • Oakwood Hospital
  • Beaumont Hospital
  • Duke University
  • Cleveland Clinic
  • Magee-Women's Hospital
  • University of Texas Southwestern Medical Center
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Botox A

Standardized Anticholinergic Regimen

Arm Description

A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets

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.

Outcomes

Primary Outcome Measures

Change in Urge Urinary Incontinence (UUI) Episodes
Change from baseline in mean number of UUI episodes over 6 month double-blind period.

Secondary Outcome Measures

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

Full Information

First Posted
July 19, 2010
Last Updated
April 30, 2018
Sponsor
NICHD Pelvic Floor Disorders Network
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT01166438
Brief Title
Anticholinergic vs. Botox Comparison Study
Acronym
ABC
Official Title
Efficacy and Impact of Botulinum Toxin A Versus Anticholinergic Therapy for the Treatment of Bothersome Urge Urinary Incontinence
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NICHD Pelvic Floor Disorders Network
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urge Urinary Incontinence, Overactive Bladder
Keywords
incontinence, overactive bladder, botox, anticholinergic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
249 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Botox A
Arm Type
Experimental
Arm Description
A single intradetrusor injection of 100U botulinum toxin A (Botox A®) plus daily oral placebo tablets
Arm Title
Standardized Anticholinergic Regimen
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Botulinum toxin A (Botox A®)
Other Intervention Name(s)
(Botox A®)
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.
Intervention Type
Drug
Intervention Name(s)
Solifenacin 5mg
Other Intervention Name(s)
Vesicare
Intervention Description
Oral Solifenacin 5mg once a day for up to 6 months
Intervention Type
Drug
Intervention Name(s)
Solifenacin 10mg
Other Intervention Name(s)
Vesicare
Intervention Description
Oral Solifenacin 10mg once a day for up to 4 months
Intervention Type
Drug
Intervention Name(s)
Trospium chloride
Other Intervention Name(s)
Sanctura
Intervention Description
Oral Trospium chloride XR 60mg once a day for up to 2 months
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
Title
Efficacy
Description
Efficacy outcomes assessed reduction and resolution of incontinence, including urgency urinary incontinence (UUI).
Time Frame
6 months
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
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Visco, MD
Organizational Affiliation
Duke University
Official's Role
Study Chair
Facility Information:
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
USCD Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Kaiser Permanente
City
San Diego
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Oakwood Hospital
City
Dearborn
State/Province
Michigan
ZIP/Postal Code
48124
Country
United States
Facility Name
Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Magee-Women's Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33620895
Citation
Hendrickson WK, Amundsen CL, Rahn DD, Meyer I, Bradley MS, Smith AL, Myers DL, Jelovsek JE, Lukacz ES. Comparison of 100 U With 200 U of Intradetrusor OnabotulinumToxinA for Nonneurogenic Urgency Incontinence. Female Pelvic Med Reconstr Surg. 2021 Mar 1;27(3):140-146. doi: 10.1097/SPV.0000000000001020.
Results Reference
derived
PubMed Identifier
27564385
Citation
Visco AG, Zyczynski H, Brubaker L, Nygaard I, Xu X, Lukacz ES, Paraiso MF, Greer J, Rahn DD, Meikle SF, Honeycutt AA. Cost-Effectiveness Analysis of Anticholinergics Versus Botox for Urgency Urinary Incontinence: Results From the Anticholinergic Versus Botox Comparison Randomized Trial. Female Pelvic Med Reconstr Surg. 2016 Sep-Oct;22(5):311-6. doi: 10.1097/SPV.0000000000000277.
Results Reference
derived
PubMed Identifier
26516810
Citation
Visco AG, Brubaker L, Jelovsek JE, Wilson TS, Norton P, Zyczynski HM, Spino C, Sirls L, Nguyen JN, Rahn DD, Meikle SF, Nolen TL; Pelvic Floor Disorders Network. Adherence to Oral Therapy for Urgency Urinary Incontinence: Results from the Anticholinergic Versus Botox Comparison (ABC) Trial. Female Pelvic Med Reconstr Surg. 2016 Jan-Feb;22(1):24-8. doi: 10.1097/SPV.0000000000000215.
Results Reference
derived
PubMed Identifier
23036134
Citation
Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF, Menefee SA, Schaffer J, Lowder J, Khandwala S, Sirls L, Spino C, Nolen TL, Wallace D, Meikle SF; Pelvic Floor Disorders Network. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med. 2012 Nov 8;367(19):1803-13. doi: 10.1056/NEJMoa1208872. Epub 2012 Oct 4.
Results Reference
derived
PubMed Identifier
22008247
Citation
Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF, Menefee SA, Schaffer J, Wei J, Chai T, Janz N, Spino C, Meikle S; Pelvic Floor Disorders Network. Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial. Contemp Clin Trials. 2012 Jan;33(1):184-96. doi: 10.1016/j.cct.2011.09.019. Epub 2011 Oct 8.
Results Reference
derived
Links:
URL
http://www.pfdnetwork.org
Description
Pelvic Floor Disorders Network
URL
https://pfdnetwork.azurewebsites.net/ResearchStudies/CompletedStudies/ABC.aspx
Description
ABC Study Information

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Anticholinergic vs. Botox Comparison Study

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