Efficacy of solifenacin, mirabegron and combination therapy in children with daytime urinary incontinence (BeDry): Protocol for a randomized single-blinded controlled trial (Preprint)

BACKGROUND According to International Children’s Continence Society (ICCS), 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 primarily in non-randomized trials. OBJECTIVE The primary objective 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 treatment of daytime urinary incontinence among children aged 5 to 14 years who are none complete responders to respectively 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 dose and monotherapy in low doses as supplementary comparisons. Additionally, the secondary objective is to evaluate side effects, safety, and tolerability of the medical treatment as well as the effect of treatment on well-being and quality of life. METHODS Children aged 5-14 years diagnosed with daytime urinary incontinence refractory to standard urotherapy will be randomized to four treatment groups, randomization 1:1:1:1. Initially two groups will receive solifenacin 5 mg and two groups will receive mirabegron 25 mg. After 6 weeks, non-complete respondsers will receive add-on treatment according to their primary randomization group; group 1A will reviece 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, group 2B will receive mirabegron 25 mg and add-on solifenacin 5 mg. Total treatment period will be 18 weeks. The primary endpoint measure is treatment response assessed by change from visit 2 to end of study, according to number of wet days pr. 7 days by DryPie. RESULTS Participants will be included from June 2024 to December 2027. CONCLUSIONS The trial has the potential to optimize medical treatment of children with daytime urinary incontinence, to shorten the treatment period, diminish side effects and minimized unnecessary medical expenses. CLINICALTRIAL EU CT 2023-510187-13-00