Role of Combination Therapy in Women With Refractory Overactive Bladder

Summary

Defined by the International Continence Society (ICS) as urinary "urgency, with or without urge incontinence, usually with frequency and nocturia", overactive bladder (OAB) presents as challenging syndrome to treat. OAB is a very prevalent condition, affecting between 11.8% to 16% of the population with equal impact on women and men and growing prevalence with age. OAB is associated with a significant financial burden to both patients and the health care system with a estimated cost of US $82.6 billion in 2020. Traditionally, a stepwise approach has been taken in managing OAB; starting first with lifestyle modifications, followed by anticholinergic or beta-3-agonist medications as the second line, and lastly, intradetrusor onabotulinumtoxinA injections, percutaneous tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM) as third line options. Given the limitations of this stepwise approach in patients with refractory OAB, combination therapy offers patients an increasing number of treatment options but the literature surrounding the efficacy of combination therapy is somewhat limited. A 2019 systematic review revealed there were only 32 studies in the current OAB literature that explored the role of combination therapy, and the majority of these studies examined the effect of lifestyle modifications with another intervention strategy, highlighting an untapped area of research5.

To date, there has only been a single pilot study conducted in Taiwan examining the effect of intradetrusor onabotulinumtoxinA injections with the addition of mirabegron for patients with refractory OAB. This study by Wang et al. explored the therapeutic impact of adding either an anticholinergic, solifenacin, or a beta-3 agonist, mirabegron, to intradetrusor onabotulinumtoxinA injections as compared to each other as well as patients receiving onabotulinumtoxinA alone. Ninety patients were enrolled with 30 patients allocated to the solifenacin arm, 31 to the mirabegron arm, and 29 to the control group. While the baseline data among the three arms was comparable, the percentage of OAB wet in the mirabegron plus onabotulinumtoxinA group was significantly less at 3-, 6-, 9-, and 12-month intervals than the solifenacin plus onabotulinumtoxinA and the onabotulinumtoxinA alone groups. While this pilot study reveals the potential additive benefit of a beta-3 agonist to intradetrusor onabotulinumtoxinA, no further studies have been performed to date and there are no studies regarding the additive benefit of vibegron, which has a more tolerable side effect profile and is not as limited by as many contraindications as mirabegron. If vibegron can potentiate the effect of intradetrusor onabotulinumtoxinA, this presents a new treatment strategy for OAB and could offer patients an additional line of therapy before having to pursue more invasive and costly management option of sacral neuro modulation.

Conditions

• Overactive Bladder Syndrome

Interventions

DRUG

Vibegron 75mg

Each patient will undergo intradetrusor onabotulinumtoxinA injections of 100U either in the office or in the operating room depending on patient and provider preference. Patients will begin taking vibegron 75mg daily or a placebo pill daily starting the day of their procedure and continue for 3 months.

DRUG

Placebo

Each patient will undergo intradetrusor onabotulinumtoxinA injections of 100U either in the office or in the operating room depending on patient and provider preference. Patients will begin taking vibegron 75mg daily or a placebo pill daily starting the day of their procedure and continue for 3 months.

Sponsors & Collaborators

• University of Alabama at Birmingham

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-01

Primary Completion

2025-12-01

Completion

2025-12-31