Beta-Agonist Versus OnabotulinumtoxinA Trial for Urgency Urinary Incontinence (BEST)

The goal of this clinical trial is to compare treatment outcomes between an oral medication (beta agonist) versus onabotulinumtoxinA injections in women with urgency urinary incontinence (UUI).

Participants will be randomly selected to receive one of the two treatments. The primary outcome measure will be at 3 months, and women will be followed for a total of 12 months.

Based on patient expert input, there are 2 primary outcomes: Treatment satisfaction and urinary symptom severity.

Study Overview

• Status: Recruiting
• Conditions: Urgency Urinary Incontinence
• Intervention / Treatment: Drug: OnabotulinumtoxinA 100 UNT [Botox]; Drug: Beta3-Agonists, Adrenergic [Mirabegron/Vibegron]

Detailed Description

The purpose of this study is to directly compare 2 primary outcomes (Treatment satisfaction and urinary symptom severity) between beta agonist oral medication versus onabotulinumtoxinA intradetrusor bladder injection for the treatment of UUI.

The study will also compare secondary outcomes identified as important by patients. At the end of the study, the investigators will have patient and stakeholder-derived comparative outcomes between these 2 commonly available treatment categories. A stakeholder and community engagement (CE) plan will be developed and implemented. The investigators will also develop a model to help guide patients and providers through this decision process.

SPECIFIC AIMS Specific Aim 1: Compare the efficacy of beta agonist versus onabotulinumtoxinA on patient-important treatment outcomes at 3 months in women with UUI.

This multi-center, randomized clinical trial (RCT) includes 5 sites across the U.S. Two co-primary outcomes will be measured using validated patient-reported outcomes (PROs), selected by patients: Co-primary outcome 1: Symptom severity, measured by change in Overactive Bladder Questionnaire-Symptom Bother Scale (OAB-q-SS) score.

Co-primary outcome 2: Treatment satisfaction, measured by the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General (FACIT-TS-G), powered based on a single item.

Specific Aim 2: Compare secondary patient-important outcomes. Direct comparisons between intervention effects on secondary outcomes chosen by patients and stakeholders, including adverse events, UUI quality of life, global improvement, and sexual function.

Specific Aim 3: Use predictive modeling to help stakeholders better determine expected outcomes after treatment with beta agonist versus onabotulinumtoxinA.

Comparators: Beta agonist oral medication (mirabegron or vibegron) versus intradetrusor onabotulinumtoxinA.

Both beta-agonists and onabotulinumtoxinA are US Food and Drug Administration (FDA) approved for the treatment of UUI, and widely available options with established efficacy.

432 women will be randomly assigned to each treatment option: 216 to beta agonist oral medication and 216 to intradetrusor onabotulintoxinA. Women will be undergo outcomes assessments at 3, 6, 9, and 12 months. The primary outcome measure will be at 3 months.

• Study Type: Interventional
• Enrollment (Estimated): 432
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ann Meers, BS, RN; Phone Number: 48228 401-274-1100; Email: Ameers@wihri.org
• Study Contact Backup: Name: Sara Veera, BS; Phone Number: 48222 401-274-1100; Email: sveera@wihri.org

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Sunita Patel; Phone Number: 205-996-0241; Email: sunitapatel@uabmc.edu
      • Principal Investigator: Holly Richter, PhD, MD
  • California
    • San Diego, California, United States, 92093
      • Recruiting
      • University of California, San Diego
      • Principal Investigator: Emily Lukacz, MD
      • Contact: Kyle Herrala; Phone Number: 858-657-6827; Email: UrogynRSCH@ucsd.edu
  • District of Columbia
    • Washington, District of Columbia, United States, 20059
      • Recruiting
      • Howard University
      • Contact: Angela Silva; Email: asilva@thecpin.com
      • Principal Investigator: Tatiana Sanses, MD
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Recruiting
      • University of New Mexico
      • Contact: Karen Taylor; Phone Number: 505-205-4118; Email: Kataylor@salud.unm.edu
      • Contact: Cassandra Darley; Email: cjdarley@salud.unm.edu
      • Principal Investigator: Peter Jeppson, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Women & Infants Hospital of Rhode Island
      • Contact: Ann Meers, BS, RN; Phone Number: 48228 401-274-1100; Email: Ameers@wihri.org
      • Contact: Sara Veera, BS; Phone Number: 48222 401-274-1100; Email: sveera@wihri.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria*:

1. 18 years or older
2. report at least "quite a bit bothered" or worse by their UUI defined by response to OAB-q-SS item #8 "How bothered are you by urine loss associated with a strong desire to urinate?"
3. are not and do not plan to become pregnant
4. have persistent UUI defined as previous unsuccessful results after conservative and anticholinergic treatment, or are unable to tolerate or have contraindications to anticholinergics
5. are currently not taking anticholinergics or are willing to stop medication for 3 weeks prior to enrollment.
6. for participants reporting mixed urinary incontinence symptoms, participant must (a) have less bother from SUI than from UUI, defined as a response of "Not at all bothered" or only "a little bit bothered" by SUI on the Urogenital Distress Inventory item "Do you experience urine leakage related to physical activity? (walking, running, laughing, sneezing, coughing), and (b) SUI symptoms be stable (> 3 months), and (c)participant does not desire additional treatment for SUI in the upcoming 3 months.
7. Participants after unsuccessful neuromodulation trial can be eligible after a 4-week washout period.

Exclusion criteria:

1. clinical contraindication to beta-3 agonist or onabotulinumtoxinA
2. prior therapeutic trial of either study treatment
3. unevaluated hematuria, current or prior bladder malignancy
4. surgically altered detrusor muscle
5. prior pelvic radiation
6. post-void residual >150 mL in past 3 months
7. neurogenic bladder
8. pelvic floor surgery within the past 3 months
9. anticipating pelvic surgery within primary outcome follow up period (3 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intradetrusor onabotulinumtoxinA; OnabotulinumtoxinA at a dose of 100 units will be injected into the bladder per usual care pathways.	Drug: OnabotulinumtoxinA 100 UNT [Botox]; OnabotulinumtoxinA will be prepared by dissolving 100 units into 10 ml of injectable saline. The injection will be an office based procedure, performed per usual care.; Other Names: Botox
Active Comparator: Beta-3 receptor agonist oral medication; Selective beta-3 receptor agonist oral medication approved for the treatment of urgency urinary incontinence including mirabegron or vibegron. Usual clinical care standards will be used for prescribing and dosing changes. For mirabegron, dosages are 25 mg and 50 mg as clinically indicated. For vibegron, dosage is 75 mg daily by mouth as clinically indicated.	Drug: Beta3-Agonists, Adrenergic [Mirabegron/Vibegron]; The beta-agonist oral medication will be prescribed and dose adjusted per usual care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in score Overactive Bladder Questionnaire-Symptom Bother Scale (OAB-q-SS) at 3 months	8-item questionnaire measuring symptom bother of overactive bladder symptoms, higher scores indicate more bothersome symptoms	Baseline until 3 months
Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General Questionnaire (FACIT-TS-G) at 3 months	Single item "How do you rate this treatment overall" on a 5-point likert scale	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Overactive Bladder Questionnaire-Symptom Bother Scale (OAB-q-SS)	8-item questionnaire measuring symptom bother of overactive bladder symptoms	Baseline until 6, 9, 12 months
Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General Questionnaire (FACIT-TS-G) at 3 months	8-item questionnaire assessing treatment satisfaction of adults undergoing treatment for chronic conditions	6, 9, 12 months
Change in Overactive Bladder Questionnaire-Health Related Quality of Life (OAB-q-HRQL)	Overactive bladder disease specific questionnaire measuring quality of life, higher scores indicate better HRQL	Baseline to 3, 6, 9, 12 months
Change in Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-IR)	Validated tool assessing female sexual function in women with pelvic floor disorders; higher scores reflect better sexual functioning	Baseline to 3, 6, 9, 12 months
Patient global impression of improvement (PGI-I)	Global measure of patient impression of improvement, likert scale	3, 6, 9, 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Cognitive Function-Short Form	Generic cognitive function measure (8 items), higher scores indicate better function	Baseline to 3, 6, 9, 12 months

Collaborators and Investigators

• Sponsor: Women and Infants Hospital of Rhode Island
• Collaborators: Patient-Centered Outcomes Research Institute; University of California, San Diego; University of Alabama at Birmingham; Brown University; University of New Mexico; Howard University
• Investigators: Principal Investigator: Vivian Sung, MD, MPH, Women and Infants Hospital of Rhode Island; Principal Investigator: Peter Jeppson, MD, University of New Mexico

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Botox; Community Engagement; UUI; Urgency Incontinence; Beta Agonist; onabotulintoxinA
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Incontinence; Enuresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Urological Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Adrenergic beta-Agonists; Botulinum Toxins, Type A; abobotulinumtoxinA; Adrenergic Agonists; Mirabegron; Adrenergic Agents; Adrenergic beta-3 Receptor Agonists
• Other Study ID Numbers: 1895985

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified database once cleaned will be available to the team, collaborators, and broader scientific community once the primary paper is published. Requests received from outside investigators will be reviewed by the research team to ensure aims do not duplicate pre-specified objective and aims of the original protocol, and the database will be released if approved.
• IPD Sharing Time Frame: Once the primary paper is published.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No