Vaginal Estrogen vs Oral Mirabegron for Overactive Bladder

Overseen By Katherine L Dengler, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Walter Reed National Military Medical Center

Must not be taking: Anticholinergics, Beta-3 agonists

Disqualifiers: Multiple sclerosis, Parkinson's, 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: 2

Duration: 12 weeks

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for postmenopausal women with bladder issues such as frequent urination, strong urges, or nighttime urination. Researchers compare two treatments: a vaginal estrogen cream and an oral medication called Mirabegron, which relaxes the bladder muscle. Participants will be randomly assigned to one of these treatments to determine which is more effective over 12 weeks. Postmenopausal women with bothersome bladder symptoms might be suitable for this study. As a Phase 4 trial, the treatments have already received FDA approval and proven effective, and this research aims to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you have not taken anticholinergic or beta-3 agonists in the past month, so you may need to stop these medications before participating.

What is the safety track record for these treatments?

Research has shown that Mirabegron is generally well-tolerated by people with overactive bladder, reducing symptoms like urgency and frequent urination. The side effects align with existing knowledge about the drug, with no major issues reported.

Studies suggest that vaginal estrogen effectively improves bladder symptoms in postmenopausal women, reducing urinary tract infections and enhancing bladder health.

Both treatments have demonstrated safety in past studies, providing confidence in their use. However, consulting a doctor is essential to determine if these options are suitable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for overactive bladder because they offer unique approaches compared to standard options like anticholinergics or beta-3 adrenergic agonists. Vaginal estrogen, applied as a cream, directly targets local tissues to potentially improve bladder function and reduce symptoms by strengthening the vaginal and urethral tissue. This local application minimizes systemic side effects often seen with oral medications. On the other hand, mirabegron works by relaxing the bladder muscle via beta-3 adrenergic receptor stimulation, offering an oral alternative to anticholinergics, and may provide relief with fewer side effects like dry mouth or constipation. Both treatments offer fresh perspectives on managing overactive bladder by either utilizing local hormone therapy or a novel oral medication mechanism.

What evidence suggests that this trial's treatments could be effective for overactive bladder?

This trial will compare the effectiveness of vaginal estrogen and oral mirabegron for treating overactive bladder. Research has shown that vaginal estrogen can reduce symptoms of an overactive bladder, such as urgency and frequent urination, in postmenopausal women. Studies have found that it increases certain bacteria in the bladder, which may help maintain bladder health. Meanwhile, mirabegron effectively decreases the number of incontinence episodes and improves bladder function. Evidence indicates that it can reduce incontinence by about 50% compared to a placebo. Both treatments have a strong record of aiding bladder control issues, each working in different ways. Participants in this trial will receive either vaginal estrogen with a placebo oral pill or oral mirabegron with a placebo vaginal cream. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher W Heuer, DO

Principal Investigator

Urogynecology Fellow

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with overactive bladder symptoms who can read and speak English. They must have had no periods for 12 months, or certain surgeries, or high hormone levels. Women with significant pelvic issues, neurological conditions like MS or Parkinson's, a history of pelvic radiation, interstitial cystitis, frequent UTIs, or recent use of similar meds cannot join.

Inclusion Criteria

Ability to speak and read English

Your score on the OAB-q SF questionnaire is 14 or higher (which is adjusted to 20).

You are a woman who has stopped having periods for at least a year, had both ovaries removed at least a year ago, had a hysterectomy and still have ovaries and are over 55 years old, or have a specific hormone level.

Exclusion Criteria

You have severe pelvic organ prolapse and cannot use vaginal estrogen therapy.

You have a medical reason that prevents you from using vaginal estrogen or mirabegron.

You have had unexplained vaginal bleeding after menopause in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomized to receive either vaginal estradiol or oral Mirabegron for 12 weeks

12 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, completing questionnaires and diaries

4 weeks

1 visit (in-person)

Extension

Participants may opt into dual treatment with both vaginal estradiol and Mirabegron for an additional 12 weeks

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron 50 MG [Myrbetriq]
• Vaginal estrogen

Trial Overview The study compares vaginal estradiol cream against an oral beta-3 agonist called Mirabegron for treating overactive bladder in postmenopausal women. Participants will be randomly assigned to receive either the estradiol cream with a placebo pill or Mirabegron pills with a placebo cream for 12 weeks.

How Is the Trial Designed?

Group I: Vaginal Estradiol with placebo oral pill Active Control 1 Intervention

Patient will receive 0.01% estradiol cream 1/2 gram applied vaginally once nightly for two weeks then three times per week with once daily placebo oral pill

Group II: Oral Mirabegron with placebo vaginal cream Active Control 1 Intervention

Patient will receive 50 milligrams oral Mirabegron once daily and placebo vaginal cream (Medisca's VersaPro Cream Base) once nightly for two weeks then three times per week

Mirabegron 50 MG [Myrbetriq] is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Myrbetriq for:

• Overactive bladder syndrome (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in European Union as Betmiga for:

• Overactive bladder syndrome (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in Canada as Myrbetriq for:

• Overactive bladder syndrome (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in Japan as Betmiga for:

• Overactive bladder syndrome (OAB)
• Neurogenic detrusor overactivity (NDO)

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Published Research Related to This Trial

Mirabegron, a β3-adrenoceptor agonist, has been shown to effectively reduce micturition frequency and improve quality of life in patients with overactive bladder (OAB) over a 12-week treatment period, with benefits sustained for up to 52 weeks.

Compared to traditional antimuscarinics, mirabegron is generally well tolerated, with a lower incidence of dry mouth, making it a suitable alternative for patients who cannot tolerate antimuscarinics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: A Review in Overactive Bladder Syndrome. Deeks, ED.[2018]

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, a β3-adrenergic receptor agonist, significantly reduces incontinence and micturition episodes in adults with overactive bladder syndrome, based on three 12-week trials involving multiple countries.

It is generally well tolerated, with a low adverse event rate similar to placebo, and has a lower incidence of dry mouth compared to tolterodine, making it a favorable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: a review of its use in patients with overactive bladder syndrome. Sanford, M.[2021]

In a study of 33 women with overactive bladder syndrome, both mirabegron (50 mg) and tolterodine (4 mg) significantly improved urodynamic parameters, such as increasing the volume at strong desire to void and reducing daytime frequency episodes.

However, mirabegron treatment was associated with a significant decrease in total voided volume compared to tolterodine, suggesting that while both medications are effective, mirabegron may alter bladder function differently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons of the Clinical Outcomes and Urodynamic Effects of Mirabegron versus Tolterodine Treatment for Female Overactive Bladder Syndrome: A Subgroup Analysis of a Controlled, Randomised, Prospective Study. Hsiao, SM., Chang, TC., Chen, CH., et al.[2018]

In a study of 50 sexually active women with overactive bladder (OAB), treatment with Mirabegron for 12 weeks significantly improved OAB symptoms, with 59.5% achieving complete urinary continence.

Mirabegron also led to a notable enhancement in female sexual function, with 84% of participants showing improved scores on the Female Sexual Function Index, and 32% reporting no sexual dysfunction after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of Mirabegron on sexual function in women with idiopathic overactive bladder. Gubbiotti, M., Giannantoni, A., Cantaluppi, S., et al.[2020]

In a 12-week study involving Japanese female patients with overactive bladder, both mirabegron and vibegron were found to be effective, showing no significant differences in their ability to improve symptoms based on the total overactive bladder symptom scores (OABSS).

However, mirabegron demonstrated a better safety profile, with significantly fewer treatment-related adverse events (19.1% for mirabegron vs. 38.5% for vibegron), suggesting that mirabegron may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron versus vibegron in previously untreated female patients with overactive bladder: A randomized, single-clinic, open-label trial. Sato, H., Otsuka, S., Tsukada, S.[2023]

In a study of 199 postmenopausal women with treatment-naïve overactive bladder (OAB), both mirabegron and vibegron at 50 mg daily significantly improved OAB symptoms and quality of life after 12 weeks, with no significant differences between the two medications.

The safety profiles of mirabegron and vibegron were comparable, with similar rates of discontinuation due to adverse effects (6.2% for mirabegron and 6.8% for vibegron), indicating both treatments are safe options for managing OAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Mirabegron and Vibegron in Women With Treatment-Naive Overactive Bladder: A Randomized Controlled Study. Kinjo, M., Masuda, K., Nakamura, Y., et al.[2023]

In a study of 85 sexually active women with overactive bladder, those treated with mirabegron for 3 months showed significant improvements in sexual function across all measured domains, including desire, arousal, lubrication, orgasm, satisfaction, and pain.

In contrast, the control group that did not receive treatment showed no significant changes in sexual function, highlighting mirabegron's potential benefits for women experiencing both overactive bladder and sexual dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mirabegron, used for overactive bladder treatment, on female sexual function: a prospective controlled study. Zachariou, A., Mamoulakis, C., Filiponi, M., et al.[2018]

In a study of 60 treatment-naïve women with overactive bladder, mirabegron (50 mg daily for 12 weeks) significantly reduced subjective symptoms, as indicated by a decrease in the OAB symptom score from 9.4 to 6.2 points.

Mirabegron improved storage function parameters, such as the first desire to void and maximum cystometric capacity, and led to the disappearance of detrusor overactivity in 40% of patients, while not affecting voiding function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urodynamic evaluation of the efficacy of mirabegron on storage and voiding functions in women with overactive bladder. Matsukawa, Y., Takai, S., Funahashi, Y., et al.[2015]

Citations

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Mirabegron in overactive bladder patients: efficacy review ... Incontinence was reduced by approximately 50% in the mirabegron groups versus placebo. Mirabegron 50 mg was effective at week 4 with a significant reduction in ...

2. 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28762672/

Safety, efficacy, and persistence of long-term mirabegron ... Conclusions: Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405456924001810

Review – Incontinence Mirabegron Versus Placebo and ... In line with our findings, the authors concluded that relief of key OAB symptoms produced by mirabegron 50 mg is significantly better than that ...

5. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2024.1372175/full

Mirabegron 50 mg once daily, long-term treatment ... Mirabegron 50 mg once daily, long-term treatment maximizes benefit in middle-aged and older people with overactive bladder syndrome: a ...

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

Mirabegron: a review of recent data and its prospects in the ... Mirabegron was also significantly superior than placebo with regard to mean volume voided per micturition, mean number of incontinence episodes, nocturia ...

7. 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 ...

8. jurolsurgery.org jurolsurgery.org/articles/insights-into-the-management-of-overactive-bladder-what-difference-can-mirabegron-make/jus.galenos.2019.2533

Insights into the Management of Overactive Bladder Mirabegron's utility in the elderly patient population has been well supported with promising efficacy and safety outcomes. New data from a prospective placebo- ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0302283819307687

Efficacy, safety, and tolerability of mirabegron in patients ... Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7379686/

Three‐year safety, efficacy and persistence data following ... No significant increases in residual urine volume were observed. The investigators considered mirabegron to be an effective treatment for 842 of 1082 (77.8%) ...