Beta-Agonists vs Botox for Urinary Incontinence

(BEST Trial)

Recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which treatment is more effective for women with urgency urinary incontinence (UUI): an oral medication called beta-agonist (specifically Beta3-Agonists, such as Mirabegron or Myrbetriq) or Botox injections. Participants will be randomly assigned to receive either the oral medication or Botox, and researchers will assess their treatment satisfaction and symptom severity after three months. Women experiencing significant bother from UUI despite trying other treatments might be suitable candidates for this trial. The study will also monitor some participants for up to five years to evaluate the long-term effectiveness of the treatments. As a Phase 4 trial, this research involves treatments that are already FDA-approved and proven effective, aiming to understand how they benefit more patients.

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 is the safety track record for these treatments?

Research has shown that both treatments in this trial—beta3-agonists and onabotulinumtoxinA (Botox)—are generally safe for treating urinary incontinence.

For beta3-agonists, studies have found that medications like mirabegron, taken in doses of 25 mg and 50 mg, do not significantly increase the risk of urination difficulties. They are well-tolerated and help reduce incontinence episodes.

OnabotulinumtoxinA, or Botox, also has a good safety record. Research indicates it is effective and well-tolerated for people with overactive bladder. Some side effects, such as urinary tract infections (UTIs), may occur, but repeated Botox treatments have been considered safe over time.

These findings provide strong evidence for the safety of both treatments studied in this trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for urinary incontinence, which often involve lifestyle changes, pelvic floor exercises, or medications targeting different receptors, Beta3-agonists work by selectively activating beta-3 receptors to relax the bladder muscle and increase its storage capacity. This unique mechanism of action can potentially reduce urgency without the common side effects associated with other medications. On the other hand, OnabotulinumtoxinA, commonly known as Botox, is injected directly into the bladder muscle, temporarily paralyzing it to prevent overactivity. This localized approach can be especially effective for those who haven't had success with oral medications. Researchers are excited about these treatments because they offer different mechanisms and delivery methods that could provide relief for patients who have not responded well to traditional therapies.

What evidence suggests that this trial's treatments could be effective for urinary incontinence?

This trial will compare the effectiveness of Beta-3 receptor agonists, such as vibegron and mirabegron, with Botox injections for managing urinary incontinence. Research has shown that medications like vibegron and mirabegron can reduce the sudden need to urinate, frequent bathroom trips, and accidental leaks. Specifically, studies found that vibegron significantly improves these issues and helps control urine release. Similarly, mirabegron reduces leaks in people with an overactive bladder.

Botox injections have also successfully treated urinary leaks. Between 42% and 87% of patients reported no leaks after treatment, with a 60-80% reduction in leak episodes. Botox has proven effective in significantly reducing leaks, even in older adults. Research supports both treatments as effective options for managing urinary incontinence. ^{6 7 8 9 10}

Who Is on the Research Team?

Vivian Sung, MD, MPH

Principal Investigator

Women and Infants Hospital of Rhode Island

Peter Jeppson, MD

Principal Investigator

University of New Mexico

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40856729/

Vibegron in overactive bladder: a comprehensive review of ... Results: Pivotal phase III trials have demonstrated significant reductions in urgency, urinary frequency and urgency urinary incontinence with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8520873/

Efficacy of Vibegron and Mirabegron for Overactive Bladder Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks.

3. link.springer.com link.springer.com/article/10.1007/s00345-025-05799-8

Vibegron in overactive bladder: a comprehensive review of ... The trial reported significant reductions in urinary frequency, urgency episodes and UUI episodes with vibegron 50 mg and 100 mg compared with ...

4. myrbetriqhcp.com myrbetriqhcp.com/efficacy/clinical-studies/

Clinical Studies | MYRBETRIQ® (mirabegron ER tablets) Myrbetriq significantly reduced incontinence episodes per 24 hours · Co-primary Endpoint · Myrbetriq was effective in treating the symptoms of overactive bladder ...

5. auajournals.org auajournals.org/doi/10.1097/JU.0000000000003999

Efficacy and Safety of Vibegron for Persistent Symptoms ... In this trial, vibegron met all primary and secondary end points, and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3491758/

Mirabegron: a review of recent data and its prospects in the ... In addition, mirabegron 25 mg and 50 mg resulted in reduction in mean number of incontinence episodes per 24 h that was significantly lower in the age group ...

7. myrbetriqhcp.com myrbetriqhcp.com/safety/

Safety | MYRBETRIQ® (mirabegron ER tablets) A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with mirabegron; however, MYRBETRIQ ...

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1376535/full

Examining the safety of mirabegron: an analysis of real- ... Mirabegron appeared to exhibit good safety regarding urinary retention. Therefore, a reasonable interpretation of the study results was that disease progression ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2666168325014247

Efficacy and Safety of Mirabegron in Males with Overactive ... Results showed that mirabegron is effective and safe in male OAB patients, with or without BPE or receiving medications for LUTS management. Patient summary. We ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/ijcp.12433

Safety and tolerability of the β 3 -adrenoceptor agonist ... In the pooled 12-week analysis, there were seven cases of urinary retention in the placebo group (0.5%); one (0.1%) in the mirabegron 50 mg ...