Overactive BladderPhase 3Add-on-MiraNCT02476175
Add-on Mirabegron in Pediatric Patients With Refractory Overactive Bladder
A Phase 3 study testing Mirabegron in people with Overactive Bladder and Urinary Incontinence, run by CHU de Quebec-Universite Laval.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Overactive Bladder, Urinary Incontinence
- What is being tested?
- Mirabegron
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- Apr 2013to Jun 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female ≥ 5 years old and ≤17 years old
- OAB diagnostic according to the International Children Continence Society (ICCS) and less than 65% of the expected mean bladder capacity for age is confirmed (30 + (age in years x 30) mL) on a 3-day voiding diary.
- Weight and height are within the normal percentile (3rd to 97th percentile) and weight is ≥ 20 kg (3rd percentile of a 8 y.o. child, boy or girl), according to the CDC growth chart
- Ability to swallow pills
- Subjects/parents (vs. legal guardian) agree to participate to the following study and sign the informed consent
- Subjects/parents (vs. legal guardian) are able to comply with the study requirements and with the medication restrictions.
- Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. Sexually active male subjects agree to use a barrier method of birth control with female partner for the duration of the study and at least one month after ending study treatment. Sexually active male subjects agree to use a condom for the duration of the study and for at least one month after ending study treatment and the female partner to use a reliable form of birth control for the duration of the study and for at least one month after ending study treatment.
- Patients without symptom improvement or with partial response under medical therapy (at least 2 different antimuscarinic agents).
Who cannot join
- Subject has a diagnostic of dysfunctional voiding
- Post-voiding residue > 20 cc
- Polyuria (> 75 ml/kg/b.w./24 hours)
- Nephrogenic of central diabetes insipidus
- Constipation at screening (if the patient is treated and the treatment is successful, the patient will be eligible to the study)
- Urinary tract infection at visit 2-3-4. If UTI is present at the screening visit, the UTI must be treated and the success of the treatment must be documented with a negative urinalysis at visit 2.
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- QTc interval greater than 460 ms, or any increase of 30 ms on follow-up EKG (mean of 6 separate EKG-3 from visit week-2 and 3 from visit week 0). If a patient meets those criteria in the first month (initial dose), he will be excluded from the study. If the QTc change is noted after the up-titration, the dose will be decreased and EKG will be repeated within 1 week to ensure normalization of QTc.
- Clinically significant unstable medical condition or disorder
- Subject is pregnant or intends to become pregnant
- Serum creatinin more than or equal to 2 times the upper limit of normal
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than or equal to 2 times ULN, or bilirubin more than or equal to 1.5 times ULN.
- Known hypersensitivity to mirabegron or any contraindication to the use of the molecule, in accordance to the product monography (to the exception of pediatric age).
- Subject is taking medication that interact with mirabegron and this medication can't be discontinued (see appendix 1 of excluded drugs)
- Known urological pathology other than OAB that could explain urinary symptoms (as bladder stone…)
- Non-treated or non-controlled arterial hypertension
About this study
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.
Read the 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.
- Conditions
- Overactive Bladder, Urinary Incontinence
- Being tested
- Mirabegron
- Keywords
- mirabegron, antimuscarinics, beta 3 agonist, overactive bladder, children
- Medical subject headings
- Urinary Bladder, Overactive, Urinary Incontinence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirabegronDrug
Also called Myrbetriq
Patients will keep the antimuscarinic providing some efficacy and that is tolerated and Mirabegron will be added (dual therapy).
| Study group | Role | What they receive |
|---|---|---|
| Add-on Mirabegron | Experimental | 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). Receives: Drug: Mirabegron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to Urinary Incontinence as a Composite Measure of Efficacy of add-on Mirabegron
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).
Measured: up to 52 weeks
Number of Participants With Grade 2 or 3 Urgency Episodes as a Measure of Efficacy
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.
Measured: up to 52 weeks
Secondary outcomes (3)
Number of Participants With Cardio Vascular Safety
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.
Measured: Participants will be followed for the duration of the study, up to 52 weeks
Number of Participants Showing Improved Quality of Life Using the Patient Perception of Bladder Condition Scale and Voiding Diaries
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.
Measured: Participants will be followed for the duration of the study, up to 52 weeks
Number of Participants Without Variation in Heart Rate
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.
Measured: Participants will be followed for the duration of the study, up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2015 (estimated)
- Study startApr 2013
- Primary completionApr 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Overactive BladderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- CHU de Quebec-Universite Laval
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stéphane Bolduc, CHU de Quebec-Universite Laval
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02476175
- Sponsor's protocol ID
- B14-06-1998-2
- Acronym
- Add-on-Mira
- Status last verified
- Mar 2018
- First submitted
- 14 Jun 2015
- Last updated
- 24 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Add-on Mirabegron in Pediatric Patients With Refractory Overactive Bladder
- ClinicalTrials.gov ID
- NCT02476175
- Acronym / sponsor ID
- Add-on-Mira / B14-06-1998-2
- Conditions
- Overactive Bladder, Urinary Incontinence
- Keywords
- mirabegron, antimuscarinics, beta 3 agonist, overactive bladder, children
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- CHU de Quebec-Universite LavalUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 19 Jun 2015 (estimated)
- Results
- Posted 24 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Add-on Mirabegron | Experimental | Drug: MirabegronExperimental: 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). |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Male or female ≥ 5 years old and ≤17 years old
- OAB diagnostic according to the International Children Continence Society (ICCS) and less than 65% of the expected mean bladder capacity for age is confirmed (30 + (age in years x 30) mL) on a 3-day voiding diary.
- Weight and height are within the normal percentile (3rd to 97th percentile) and weight is ≥ 20 kg (3rd percentile of a 8 y.o. child, boy or girl), according to the CDC growth chart
- Ability to swallow pills
- Subjects/parents (vs. legal guardian) agree to participate to the following study and sign the informed consent
Key exclusion criteria (15 listed)
- Subject has a diagnostic of dysfunctional voiding
- Post-voiding residue > 20 cc
- Polyuria (> 75 ml/kg/b.w./24 hours)
- Nephrogenic of central diabetes insipidus
- Constipation at screening (if the patient is treated and the treatment is successful, the patient will be eligible to the study)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirabegronAlso: MyrbetriqPatients will keep the antimuscarinic providing some efficacy and that is tolerated and Mirabegron will be added (dual therapy). | Drug | Add-on Mirabegron |
Primary outcome
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.
3 secondary outcomes
Number of Participants With Cardio Vascular Safety
Time frame: Participants will be followed for the duration of the study, up to 52 weeks
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
Number of Participants Without Variation in Heart Rate
Time frame: Participants will be followed for the duration of the study, up to 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mirabegron in people with Overactive Bladder and Urinary Incontinence, run by CHU de Quebec-Universite Laval.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to Urinary Incontinence as a Composite Measure of Efficacy of add-on Mirabegron (time frame: up to 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2018.