Clinical trial NCT01166438: Anticholinergic vs. Botox Comparison Study
Official title: Efficacy and Impact of Botulinum Toxin A Versus Anticholinergic Therapy for the Treatment of Bothersome Urge Urinary Incontinence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urge Urinary Incontinence
Overactive Bladder
Keywords: incontinence
overactive bladder
botox
anticholinergic
Lead sponsor: NICHD Pelvic Floor Disorders Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2010-07-21
Enrollment: 249
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Urge Urinary Incontinence (UUI) Episodes
timeFrame: Baseline through 6 months
Secondary outcomes:
measure: Change From Baseline in Score on OABq-SF
timeFrame: Baseline through 6 months
measure: Efficacy
timeFrame: 6 months
measure: Change in PFDI-SF and PFIQ-SF Total Scores
timeFrame: Baseline through 6 months
measure: Patient Global Impression of Improvement
timeFrame: 3 and 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: USCD Medical Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: Magee-Women's Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Duke University
name: Anthony Visco, MD
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.