Bladder Therapy for Urinary Incontinence

(TRIUMPH Trial)

Recruiting at 1 trial location

Overseen By Alison Huang, MD, MAS, MPhil

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Anticholinergics, Beta-3 agonists

Disqualifiers: Dementia, Severe hepatic impairment, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates two treatments for urinary incontinence (difficulty controlling urination) to assess their effects on bladder function and overall health in older women. The study compares an anticholinergic medication, Tolterodine Tartrate ER, with a beta-3-adrenergic agonist, Mirabegron (also known as Myrbetriq), to determine which is more effective. Women who frequently experience a sudden urge to urinate, have had this issue for at least three months, and can walk to the bathroom independently may be ideal candidates for this trial. Participants will also receive guidance on managing symptoms through lifestyle changes and exercises. As a Phase 4 trial, this study involves treatments already approved by the FDA and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

If you are currently using medications for urgency incontinence or have changed doses of certain medications like dementia drugs, anticholinergics, or diuretics in the past month, you may need to stop or stabilize these before joining the trial. The protocol requires that you have not used these medications in the past month or have been on a stable dose.

What is the safety track record for these treatments?

Previous studies have shown no new safety concerns with mirabegron. It is already approved for treating symptoms of an overactive bladder, such as urgency and incontinence. However, there is a risk of not being able to fully empty the bladder, and it is important to inform a doctor if this occurs.

Research indicates that tolterodine tartrate ER helps reduce symptoms of an overactive bladder, like frequent urination and urgency. Some individuals experienced slight difficulty in completely emptying their bladders. Overall, both treatments are generally well-tolerated.

These medications have been widely used, providing extensive safety information for treating overactive bladder. Always consult a healthcare provider about any concerns or side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Mirabegron is unique because it works as a selective beta-3-adrenergic receptor agonist, which relaxes the bladder muscle, reducing urgency and frequency. Most treatments for overactive bladder, like tolterodine, are anticholinergics that block certain nerve signals to prevent bladder contractions. Researchers are excited about mirabegron since it offers a different mechanism of action, potentially leading to fewer side effects like dry mouth and constipation, which are common with anticholinergic medications. Additionally, combining these medications with behavioral self-management education could enhance overall treatment effectiveness.

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

This trial will compare different treatments for urinary incontinence related to an overactive bladder. Participants in one arm will receive mirabegron. Studies have shown that mirabegron can significantly reduce the number of incontinence episodes, with patients experiencing nearly a 50% reduction compared to those taking a placebo. It also lessens the need to urinate frequently and the sudden urge to go. Another arm will involve tolterodine tartrate ER, which has also proven effective, showing a significant decrease in episodes of urgent incontinence and reducing how often people need to urinate each day. Both treatments are generally well-tolerated and improve symptoms for many patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Alison Huang, MD, MAS, MPhil

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

The TRIUMPH study is for ambulatory older women aged 60 or above with urgency-predominant urinary incontinence and normal to mildly impaired cognitive function. Participants must have experienced urinary incontinence for at least 3 months, with episodes of sudden urgency, and be able to use the toilet without help. Exclusions include dementia diagnosis, recent medication changes affecting cognition or urination, severe liver/renal impairment, UTI, certain medical conditions like uncontrolled glaucoma or myasthenia gravis.

Inclusion Criteria

Willing to provide informed consent and adhere to study procedures throughout the length of the study

I have had urinary incontinence for at least 3 months.

I have had at least 2 sudden urges to urinate that I couldn't control in the last week.

Exclusion Criteria

I haven't changed any medications that affect how often I urinate in the last month.

I currently have a urinary tract infection.

History of allergy or sensitivity to either of the study medications or an ingredient in the placebo or study medication capsule

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either anticholinergic bladder therapy, beta-3-adrenergic agonist bladder therapy, or placebo, along with behavioral self-management education

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Participants are assessed for changes in cognitive, urinary, and functional outcomes

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron
• Placebo
• Tolterodine Tartrate ER

Trial Overview This trial compares two medications—Tolterodine Tartrate ER (an anticholinergic) and Mirabegron (a beta-3-adrenergic agonist)—against a placebo to see their effects on cognitive and urinary functions in older women with overactive bladders. It's a randomized double-blind study where participants won't know which treatment they're getting.

How Is the Trial Designed?

Group I: Anticholinergic bladder medication plus behavioral self-management education Active Control 1 Intervention

Tolterodine tartrate is a muscarinic receptor antagonist designed to treat urgency incontinence, urgency, and frequency associated with overactive bladder. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.

Group II: Beta-3-adrenergic agonist medication plus behavioral self-management education Active Control 1 Intervention

Mirabegron, currently sold under the brand name Mybetriq by Astellas Pharma, is a selective beta-3-adrenergic receptor agonist approved for treatment of urgency urinary incontinence, urgency, and frequency associated with overactive bladder. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.

Group III: Placebo medication plus behavioral self-management education Placebo Group 1 Intervention

Microcrystalline cellulose placebo encapsulated to appear identical to tolterodine and mirabegron medication will be prepared by a compounding pharmacy. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.

Mirabegron is already approved in United States, European Union for the following indications:

Approved in United States as Myrbetriq for:

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

Approved in European Union as Mirabegron for:

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

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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]

Mirabegron was effective in treating overactive bladder (OAB) in 85.2% of newly diagnosed patients and 61.6% of patients unresponsive to antimuscarinics, showing significant improvements in OAB symptoms without significant differences compared to antimuscarinic therapy.

The treatment had a low incidence of adverse events (8.4%), all of which were mild and resolved spontaneously, indicating that mirabegron is a safe option for managing OAB symptoms, including those related to benign prostatic hyperplasia (BPH).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β3-Adrenoceptor agonist mirabegron is effective for overactive bladder that is unresponsive to antimuscarinic treatment or is related to benign prostatic hyperplasia in men. Otsuki, H., Kosaka, T., Nakamura, K., et al.[2021]

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 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]

Mirabegron (50 mg and 100 mg) significantly reduces incontinence episodes, urgency, and frequency of urination compared to placebo, and shows a slight improvement in nocturia compared to tolterodine, based on a meta-analysis of 8 studies involving 10,248 patients.

Both doses of mirabegron have a similar safety profile to placebo, while tolterodine is associated with a higher risk of adverse events; however, mirabegron 100 mg may have a slight increased risk of hypertension and cardiac arrhythmia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis on the efficacy and tolerability of mirabegron for the treatment of storage lower urinary tract symptoms/overactive bladder: Comparison with placebo and tolterodine. Sebastianelli, A., Russo, GI., Kaplan, SA., et al.[2019]

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]

In a 12-week study involving 1,126 patients with overactive bladder, mirabegron 50 mg once daily significantly reduced the mean number of micturitions per day compared to placebo, demonstrating its efficacy in managing OAB symptoms.

The safety profile of mirabegron was comparable to that of tolterodine, with drug-related adverse events occurring in 15.8% of patients taking mirabegron, indicating it is a safe option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a randomized, double-blind, parallel-group, placebo- and active-controlled, multicenter study of mirabegron, a β3-adrenoceptor agonist, in patients with overactive bladder in Asia. Kuo, HC., Lee, KS., Na, Y., et al.[2015]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5014049/

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

Mirabegron 50 mg once daily, long-term treatment ... There were almost 0.48 fewer incontinence events per 24 h in the mirabegron 25 mg groups than in the placebo groups (MD for incontinence ...

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. 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 In this study, mirabegron 50 mg was found to be significantly more efficacious than placebo for all efficacy measures, including micturition frequency, UUI, dry ...

6. myrbetriqhcp.com myrbetriqhcp.com/isi/

Important Safety Information | MYRBETRIQ® (mirabegron ... MYRBETRIQ is contraindicated in patients with known hypersensitivity reactions to mirabegron or any inactive ingredients of the tablet.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK538513/

Mirabegron - StatPearls - NCBI Bookshelf Mirabegron is used to treat urgency, urge urinary incontinence, and increased urinary frequency found in the overactive bladder.

8. mayoclinic.org mayoclinic.org/drugs-supplements/mirabegron-oral-route/description/drg-20075675

Mirabegron (oral route) - Side effects & dosage Mirabegron works on the muscles of the bladder to increase the amount of urine your bladder can hold and prevent them from causing incontinence.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0302283819307523

Safety and Efficacy of Mirabegron: Analysis of a Large ... No previously unreported safety concerns were identified. Improvements in efficacy (mean number of incontinence episodes/24 h, micturitions/24 h, urgency ...

10. myrbetriq.com myrbetriq.com/living-with-overactive-bladder/

What Is Overactive Bladder (OAB)? MYRBETRIQ may increase your chances of not being able to empty your bladder. Tell your doctor right away if you have trouble emptying your bladder or you have a ...