Add-on Mirabegron in Pediatric Patients With Refractory Overactive Bladder
Condition: Overactive Bladder; Urinary Incontinence
MeSH terms: Urinary Incontinence; Urinary Bladder, Overactive
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Mirabegron
Intervention type(s): Drug
Intervention description(s): Patients will keep the antimuscarinic providing some efficacy and that is tolerated and Mirabegron will be added (dual therapy).
Other intervention name(s): Myrbetriq
Intervention MeSH terms: Mirabegron
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: mirabegron; antimuscarinics; beta 3 agonist; overactive bladder; children