Add-on Mirabegron in Pediatric Patients With Refractory Overactive Bladder (Add-on-Mira)
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|ClinicalTrials.gov Identifier: NCT02476175|
Recruitment Status : Completed
First Posted : June 19, 2015
Results First Posted : April 24, 2018
Last Update Posted : April 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Overactive Bladder Urinary Incontinence||Drug: Mirabegron||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Add-on Mirabegron in Pediatric Patients With Refractory Overactive Bladder|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||June 2016|
Experimental: Add-on Mirabegron
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).
Patients will keep the antimuscarinic providing some efficacy and that is tolerated and Mirabegron will be added (dual therapy).
Other Name: Myrbetriq
- Response to Urinary Incontinence as a Composite Measure of Efficacy of add-on Mirabegron [ Time Frame: up to 52 weeks ]Results were based on the International Children's Continence Sociéty classification. Parents or patients supervised by their parents rated symptom relief on a questionnaire as complete cure (definied as dryness) or partial response (reduction of 50% to 99% in incontinence episodes).
- Number of Participants With Grade 2 or 3 Urgency Episodes as a Measure of Efficacy [ Time Frame: up to 52 weeks ]On voiding diary, participants described their urgency according to the Canadian Urological Association voiding diary, range 0 to 3 at study entry and at study end.
- Number of Participants With Cardio Vascular Safety [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]Cardiovascular safety: mean difference in blood pressure (Variation in blood pressure: systolic ±20 mmHg, diastolic ±15 mmHg), blood pressure was taken at each visit and at the study end.
- Number of Participants Showing Improved Quality of Life Using the Patient Perception of Bladder Condition Scale and Voiding Diaries [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
Effectiveness will also be assessed using the Patient Perception of Bladder Condition (PPBC) scale on a 6-point scale ranging from 1 to 6 ( 1 is the best score and 6 is the worst score), at study initiation, every visit and at the study end.
Results will be documented based on subjective relief of symptoms and objective voiding diaries.
Participants perception of bladder condition score at initiation of treatment was:4 and at last follow up score was: 2.
- Number of Participants Without Variation in Heart Rate [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]Cardiovascular safety: mean difference in heart rate (with variation in heart rate increase of more than 20%). Heart rate was taken at initiation of study drug, at each visit and at the study end.