Anticholinergic vs. Botox Comparison Study

NCT01166438 | Completed Phase 3 Results DMC

• 9 other identifiers: PFDN 172U01HD0412492U10HD0412502U10HD0412612U10HD0412671U10HD0541361U10HD0542141U10HD0542151U10HD054241
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 11

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.

Conditions

Urge Urinary Incontinence; Overactive Bladder

Keywords

incontinence; overactive bladder; botox; anticholinergic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Baseline in Score on OABq-SF

  Baseline through 6 months

• Efficacy

  6 months

• Change in PFDI-SF and PFIQ-SF Total Scores

  Baseline through 6 months

• Patient Global Impression of Improvement

  3 and 6 months

Study Arms (2)

Botox A

EXPERIMENTAL

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

Drug: Botulinum toxin A (Botox A®)

Standardized Anticholinergic Regimen

ACTIVE COMPARATOR

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; Drug: Solifenacin 10mg; Drug: Trospium chloride

Interventions

Botulinum toxin A (Botox A®) 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.

Also known as: (Botox A®)

Botox A

Solifenacin 5mg DRUG

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

Also known as: Vesicare

Standardized Anticholinergic Regimen

Solifenacin 10mg DRUG

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

Also known as: Vesicare

Standardized Anticholinergic Regimen

Trospium chloride DRUG

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

Also known as: Sanctura

Standardized Anticholinergic Regimen

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (11)

The University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

USCD Medical Center

La Jolla, California, 92037, United States

Location

Kaiser Permanente

San Diego, California, 92037, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Oakwood Hospital

Dearborn, Michigan, 48124, United States

Location

Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Magee-Women's Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (6)

• 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.

  PMID: 38651909 DERIVED

• 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.

  PMID: 33620895 DERIVED

• 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.

  PMID: 27564385 DERIVED

• 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.

  PMID: 26516810 DERIVED

• 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.

  PMID: 23036134 DERIVED

• 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.

  PMID: 22008247 DERIVED

MeSH Terms

Conditions

Urinary Incontinence, Urge; Urinary Bladder, Overactive

Interventions

Botulinum Toxins, Type A; Solifenacin Succinate; trospium chloride

Condition Hierarchy (Ancestors)

Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Marie Gantz
• Organization: RTI International

mgantz@rti.org

919-597-5110

Study Officials

• Anthony Visco, MD

  Duke University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2010
• First Posted: July 21, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 2, 2018
• Results First Posted: December 6, 2017

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)