Bladder Therapy for Urinary Incontinence

(TRIUMPH Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Alison Huang, MD, MAS, MPhil

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: Anticholinergics, Beta-3 agonists

Disqualifiers: Dementia, Severe hepatic impairment, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two types of bladder medications in older women with bladder control issues. One medication blocks signals to the bladder, and the other helps the bladder hold more urine. The goal is to see which treatment works best and how they affect overall function.

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.

Is mirabegron safe for treating urinary incontinence?

Mirabegron is generally considered safe for treating urinary incontinence and other bladder issues. Studies show that it has a similar rate of side effects as a placebo (a dummy treatment) and a low risk of causing heart rhythm problems. It is well tolerated in both adults and children. ^{1 2 3 4 5}

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

Mirabegron is unique because it is a β3-adrenergic receptor agonist, which means it works by relaxing the bladder muscle to increase its capacity, unlike other treatments that often target different pathways. It is generally well-tolerated, with a lower risk of dry mouth compared to tolterodine, and it can be used in both adults and children with specific formulations for each age group. ^{2 5 6 7 8}

Research Team

Alison Huang, MD, MAS, MPhil

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Mirabegron (Beta-3 Adrenergic Agonist)
• Placebo (Drug)
• Tolterodine Tartrate ER (Anticholinergic)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

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, 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 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]

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]

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]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. [2021]

3. Netherlands 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. [2021]

4. United States 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. [2015]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. Australia 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. [2018]

7. Australia 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. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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