Efficacy of Solifenacin, Mirabegron, and Combination Therapy in Children With Daytime Urinary Incontinence (BeDry): Protocol for a Randomized Single-Blinded Controlled Trial

Abstract

Background: According to International Children's Continence Society, the first-line treatment of children with daytime urinary incontinence is standard urotherapy, eventually followed by pharmacotherapy of anticholinergics. The effect of medical treatment is sparsely investigated and has been investigated primarily in nonrandomized trials.

Objective: The primary objective of this trial is to evaluate if (1) combination therapy of solifenacin and mirabegron in low doses is superior to monotherapy of solifenacin in high dose and if (2) combination therapy of mirabegron and solifenacin in low doses is superior to monotherapy of mirabegron in high dose in the treatment of daytime urinary incontinence among children aged 5-14 years who are noncomplete responders to monotherapy of solifenacin in low dose or monotherapy of mirabegron in low dose. The secondary objective is to evaluate the treatment response of combination therapy of solifenacin and mirabegron in low doses, monotherapy in high doses, and monotherapy in low doses as supplementary comparisons. Additionally, the secondary objective is to evaluate the side effects, safety, and tolerability of the medical treatment as well as the effect of the treatment on the well-being and quality of life.

Methods: Children aged 5-14 years diagnosed with daytime urinary incontinence refractory to standard urotherapy will be randomized 1:1:1:1 to 4 treatment groups. Initially, 2 groups will receive solifenacin 5 mg and 2 groups will receive mirabegron 25 mg. After 6 weeks, noncomplete responders will receive add-on treatments according to their primary randomization group. Group 1A will receive solifenacin 5 mg and add-on solifenacin 5 mg, group 1B will receive solifenacin 5 mg and add-on mirabegron 25 mg, group 2A will receive mirabegron 25 mg and add-on mirabegron 25 mg, and group 2B will receive mirabegron 25 mg and add-on solifenacin 5 mg. The total treatment period will be 18 weeks. The primary end point measure is treatment response assessed by change from visit 2 to the end of the study, according to the number of wet days per 7 days by DryPie.

Results: The BeDry study was approved by Clinical Trials in the European Union on June 12, 2024. Recruitment began on June 27, 2024, and will continue until 236 patients are included, which is expected to occur by September 2026. As of April 2025, 75 participants are included.

Conclusions: This trial has the potential to optimize the medical treatment of children with daytime urinary incontinence, shorten the treatment period, diminish the side effects, and minimize unnecessary medical expenses.

Trial registration: Clinical Trials in the European Union EUCT 2023-510187-13-00; https://tinyurl.com/2hva7ph8; ClinicalTrials.gov NCT06551246; https://clinicaltrials.gov/study/NCT06551246.

International registered report identifier (irrid): PRR1-10.2196/63588.

Keywords: Denmark; children; mirabegron; monotherapy; multicenter; outpatient clinics; overactive bladder; pediatric; pharmacotherapy; protocol; randomized controlled trial; solifenacin; teenager; urinary incontinence; urotherapy.

Figure 1

Study flowchart.

Figure 2

Danish translation of DryPie, developed by Bower et al [15]. Green: dry; yellow: wet underpants; red: wet trousers; blue: wet socks; Mandag: Monday; Tirsdag: Tuesday; Onsdag: Wednesday; Torsdag: Thursday; Fredag: Friday; Lørdag: Saturday; Søndag: Sunday.