Anticholinergic vs. Botox Comparison Study

NCT ID: NCT01166438

Last Updated: 2018-05-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

249 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2012-05-31

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.

Conditions

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Urge Urinary Incontinence Overactive Bladder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Botox A

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

Group Type EXPERIMENTAL

Botulinum toxin A (Botox A®)

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Solifenacin 5mg

Intervention Type DRUG

Oral Solifenacin 5mg once a day for up to 6 months

Solifenacin 10mg

Intervention Type DRUG

Oral Solifenacin 10mg once a day for up to 4 months

Trospium chloride

Intervention Type DRUG

Oral Trospium chloride XR 60mg once a day for up to 2 months

Interventions

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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.

Intervention Type DRUG

Solifenacin 5mg

Oral Solifenacin 5mg once a day for up to 6 months

Intervention Type DRUG

Solifenacin 10mg

Oral Solifenacin 10mg once a day for up to 4 months

Intervention Type DRUG

Trospium chloride

Oral Trospium chloride XR 60mg once a day for up to 2 months

Intervention Type DRUG

Other Intervention Names

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(Botox A®) Vesicare Vesicare Sanctura

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.
Minimum Eligible Age

21 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

NICHD Pelvic Floor Disorders Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anthony Visco, MD

Role: STUDY_CHAIR

Duke University

Locations

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The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

USCD Medical Center

La Jolla, California, United States

Site Status

Kaiser Permanente

San Diego, California, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Oakwood Hospital

Dearborn, Michigan, United States

Site Status

Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Magee-Women's Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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Choi BI, Fontes Noronha M, Kaindl J, Wolfe AJ. Complete genome sequences of Aerococcus loyolae ATCC TSD-300T, Aerococcus mictus ATCC TSD-301T, and Aerococcus tenax ATCC TSD-302T. Microbiol Resour Announc. 2024 Jun 11;13(6):e0015624. doi: 10.1128/mra.00156-24. Epub 2024 Apr 23.

Reference Type DERIVED
PMID: 38651909 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33620895 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27564385 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26516810 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23036134 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22008247 (View on PubMed)

Other Identifiers

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2U01HD041249

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2U10HD041250

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2U10HD041261

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2U10HD041267

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U10HD054136

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U10HD054214

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U10HD054215

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U10HD054241

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PFDN 17

Identifier Type: -

Identifier Source: org_study_id

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