Clinical trial NCT02476175
Conditions: Overactive Bladder Urinary Incontinence
Keywords: mirabegron antimuscarinics beta 3 agonist overactive bladder children
Sponsor: CHU de Quebec-Universite Laval
Start date: 2013-04-01; Completion date: 2016-06-01
Enrollment: 35 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective is to evaluate the efficacy and safety of adding mirabegron to an antimuscarinic to treat urinary incontinence in children with Overactive Bladder that are refractory to antimuscarinics.

Detailed description:
Overactive bladder (OAB) is a highly prevalent disorder in the pediatric population. This condition comprises many urinary symptoms, such as urgency, increased daytime frequency of micturition, urge incontinence and nocturia. These symptoms are especially troublesome for the pediatric patients and their family since it causes embarrassment and it limits everyday activities and impairs children's development. Furthermore, serious complications are seen if this condition is not treated properly, as urinary tract infection, vesico-ureteral reflux and dysfunctional voiding. Antimuscarinic agents are the current pharmacologic mainstay for OAB. Many side effects are reported with the clinical use of antimuscarinics. Oxybutynin is the most widely antimuscarinic agent used in the pediatric population and is the only molecule approved by Health Canada for children with OAB. However, some patients have a suboptimal response to antimuscarinic and many experience side effects. Children with OAB therefore represent a disease population with a need for an alternative effective, safe and well-tolerated therapy to help manage the overactive detrusor, reducing or preventing incontinence.

Mirabegron, a β3-adrenoceptor (β3-AR) agonist approved for the treatment of OAB symptoms in the adult population, is the first of a new class of compounds with a different mechanism of action. The recommended starting dose of mirabegron is 25mg, which can be increased to 50mg, based on individual efficacy and tolerability. Side effects commonly reported with antimuscarinics were not observed more often with mirabegron than with placebo (headache 2.0%, dry mouth 2.0%, constipation 1.6%). Several Phase II and III studies have shown significant improvement in clinical OAB symptoms in adults treated with mirabegron with a favorable tolerability profile. Mirabegron has not been studied yet for pediatric patients and no recommendation with regards to its use has been issued by the manufacturer nor medical regulatory bodies.

A prospective open-label study, using an adjusted-dose regimen of mirabegron (25-50mg) added to the existing antimuscanic treatment (dual treatment), including pediatric patients with refractory urinary incontinence due to OAB. This protocol was approved by the investigators' research ethics board. Patients without symptom improvement or with partial response under intensive behavioural protocol and medical therapy (at least 2 different antimuscarinic agents) will be recruited. Pprimary end-point is efficacy toward urinary continence and secondary end-points are tolerability and safety. The patients/parents satisfaction will also be recorded.

After 8 to 12 weeks on the new medication, the possibility of up-titration will be assessed. Patients and parents will be questioned on compliance, tolerability and efficacy. If the patient is taking the medication ≥80% of the time, does not have any significant side effects and still has significant OAB symptoms, the investigators will offer a dose increase (Mirabegron 50mg daily). If accepted, the medication will be provided with instructions to report any new side effects.

Subjects will complete a 3-day voiding diary prior to each medical visit to assess the efficacy of the treatment and urotherapy. Visits will be done every 3 months.

Arms: arm 1: Experimental: Add-on Mirabegron Patients without symptom improvement or with partial response under intensive behavioural protocol and medical therapy (at least 2 different antimuscarinic agents) will be recruited. They will keep the antimuscarinic and Mirabegron will be added (dual therapy).
Interventions: intervention 1: Mirabegron
Intervention descriptions: intervention 1: Patients will keep the antimuscarinic providing some efficacy and that is tolerated and Mirabegron will be added (dual therapy).

Protocol documents: