Beta-Agonists vs Botox for Urinary Incontinence

(BEST Trial)

Recruiting at 4 trial locations

Overseen By Peter Jeppson, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Women and Infants Hospital of Rhode Island

Must not be taking: Anticholinergics

Disqualifiers: Bladder malignancy, Neurogenic bladder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 months

432 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are currently taking anticholinergic medications, you will need to stop them for 3 weeks before joining the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug for urinary incontinence?

Research shows that mirabegron, a component of the treatment, is effective in improving symptoms of urinary incontinence in patients with overactive bladder. Studies have demonstrated its efficacy and safety in various populations, including those who have not responded well to other treatments. ^{1 2 3 4 5}

Is mirabegron safe for treating urinary incontinence?

Mirabegron is generally considered safe for treating urinary incontinence, with most side effects being mild or moderate, such as high blood pressure, dry mouth, constipation, and headache. Studies show no significant increase in adverse events compared to control groups, and it is safe for use in both adults and children with specific dosing guidelines. ^{1 3 6 7 8}

How does the drug mirabegron differ from other treatments for urinary incontinence?

Mirabegron is unique because it works by stimulating beta-3 adrenergic receptors, which helps relax the bladder muscle, unlike other treatments that often target different pathways. It is available as an extended-release tablet or oral suspension, making it flexible for both adults and children. ^{2 3 4 5 7}

Research Team

Vivian Sung, MD, MPH

Principal Investigator

Women and Infants Hospital of Rhode Island

Peter Jeppson, MD

Principal Investigator

University of New Mexico

Eligibility Criteria

This trial is for women at least 18 years old who are significantly bothered by urgency urinary incontinence, have tried and not benefited from standard treatments, and are not pregnant. They must be willing to stop certain medications before joining the study. Women with mixed symptoms can join if their stress urinary incontinence is less bothersome and stable.

Inclusion Criteria

I am not on anticholinergics or can stop them for 3 weeks before joining.

My main issue is urge incontinence, not stress incontinence, which has been stable for over 3 months and I don't seek treatment for stress incontinence soon.

Are not and do not plan to become pregnant

Exclusion Criteria

I have had pelvic floor surgery in the last 3 months.

I have a condition where my bladder doesn't empty properly.

I cannot take certain medications due to my health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either beta agonist oral medication or intradetrusor onabotulinumtoxinA injections for urgency urinary incontinence

12 months

Visits at 3, 6, 9, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Beta3-Agonists
• OnabotulinumtoxinA 100 UNT [Botox]

Trial Overview The trial compares two treatments for urgency urinary incontinence: an oral medication called a beta3-agonist (Mirabegron/Vibegron) versus Botox injections. Participants will be randomly assigned to one of these treatments and monitored over 12 months, focusing on treatment satisfaction and symptom severity after 3 months.

Participant Groups

Group I: Beta-3 receptor agonist oral medication Active Control 1 Intervention

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.

Group II: Intradetrusor onabotulinumtoxinA Active Control 1 Intervention

OnabotulinumtoxinA at a dose of 100 units will be injected into the bladder per usual care pathways.

Beta3-Agonists is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Myrbetriq for:

• Overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency

Approved in European Union as Betmiga for:

• Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in patients with overactive bladder syndrome

Approved in Canada as Myrbetriq for:

• Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in patients with overactive bladder syndrome

Approved in Japan as Betanis for:

• Overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency

Who Is Running the Clinical Trial?

Women and Infants Hospital of Rhode Island

Lead Sponsor

Trials

119

Recruited

59,200+

Brown University

Collaborator

Trials

480

Recruited

724,000+

University of New Mexico

Collaborator

Trials

393

Recruited

3,526,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Howard University

Collaborator

Trials

44

Recruited

15,200+

Findings from Research

In a network meta-analysis of 19 trials involving treatment-experienced patients with overactive bladder, onabotulinumtoxinA showed better outcomes than mirabegron, particularly in reducing the number of urinations and incontinence episodes.

However, mirabegron had a lower risk of urinary tract infections compared to onabotulinumtoxinA, suggesting it may be a safer option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Relative Efficacy and Safety of Mirabegron and OnabotulinumtoxinA in Patients With Overactive Bladder who Have Previously Been Managed With an Antimuscarinic: A Network Meta-analysis. Lozano-Ortega, G., Walker, D., Rogula, B., et al.[2019]

In a study of 35 children with idiopathic overactive bladder who did not respond to antimuscarinics, adding mirabegron significantly improved bladder capacity from 50% to 74% of expected levels, indicating its efficacy as an add-on therapy.

The treatment was generally well tolerated, with only mild to moderate side effects reported in seven patients, and it was deemed a safe alternative for managing urinary incontinence in this pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Therapy for Refractory Overactive Bladder in Children: A Prospective Open-Label Study. Morin, F., Blais, AS., Nadeau, G., et al.[2019]

In a 12-week study involving 83 women with urgency urinary incontinence (UUI) treated with mirabegron, those who showed symptom improvement had a significantly richer and more diverse urobiome compared to nonresponders.

The findings suggest that changes in the urobiome may be linked to the effectiveness of mirabegron in treating UUI, indicating a potential mechanism for symptom improvement that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptom improvement with mirabegron treatment is associated with urobiome changes in adult women. Halverson, T., Mueller, ER., Brubaker, L., et al.[2022]

In a study involving 1139 patients with overactive bladder, mirabegron 50 mg was found to significantly reduce the number of daily micturitions and urgency episodes compared to placebo, demonstrating its efficacy in treating OAB symptoms.

The safety profile of mirabegron was favorable, with adverse events occurring at rates similar to placebo, and most side effects were mild, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III, randomised, double-blind, placebo-controlled study of the β3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder. Yamaguchi, O., Marui, E., Kakizaki, H., et al.[2022]

In a study of 63 patients with chronic neurogenic detrusor overactivity, mirabegron significantly reduced urinary incontinence from 60.3% to 38.1% and improved bladder capacity and detrusor compliance.

Mirabegron was well-tolerated, with no patients discontinuing treatment due to side effects, suggesting it has a good safety profile and may allow for lower doses of other medications used for NDO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effects of Mirabegron in Patients with Chronic Neurogenic Detrusor Overactivity - A Retrospective Cohort Study. Krebs, J., Pannek, J., Rademacher, F., et al.[2022]

Mirabegron effectively reduces symptoms of overactive bladder, such as incontinence episodes and frequency of urination, as shown in Phase III trials involving various doses, and is particularly beneficial for patients who previously found antimuscarinics ineffective or intolerable.

The treatment is generally safe, with most side effects being mild to moderate, including hypertension and dry mouth, and it has a lower incidence of dry mouth compared to antimuscarinics, making it a suitable option for older patients as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of the β3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome. Vij, M., Drake, MJ.[2020]

Mirabegron, a beta-3 adrenergic agonist, has been approved for treating neurogenic detrusor overactivity in pediatric patients aged 3 years and older, marking a significant advancement in pediatric urology.

The medication is available in two formulations: extended-release tablets for children weighing 35 kg or more, and an extended-release oral suspension for those under 35 kg, emphasizing the importance of appropriate dosing based on weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. Keam, SJ.[2021]

Mirabegron significantly improves bladder compliance, reduces urinary incontinence episodes, and enhances quality of life in patients with neurogenic lower urinary tract dysfunction, based on a meta-analysis of four randomized controlled trials involving 245 patients.

The treatment is considered safe, as there were no significant differences in adverse events or serious side effects like arrhythmias and hypertension when compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Mirabegron for the Treatment of Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review and Meta-analysis. Zhang, D., Sun, F., Yao, H., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

The Relative Efficacy and Safety of Mirabegron and OnabotulinumtoxinA in Patients With Overactive Bladder who Have Previously Been Managed With an Antimuscarinic: A Network Meta-analysis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Dual Therapy for Refractory Overactive Bladder in Children: A Prospective Open-Label Study. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Symptom improvement with mirabegron treatment is associated with urobiome changes in adult women. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Phase III, randomised, double-blind, placebo-controlled study of the β3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Real-World Effects of Mirabegron in Patients with Chronic Neurogenic Detrusor Overactivity - A Retrospective Cohort Study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Clinical use of the β3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Mirabegron for the Treatment of Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review and Meta-analysis. [2021]