Urinary Bladder, NeurogenicPhase 2/3NCT02044510
Urodynamic and Clinical Efficacy of Mirabegron for Neurogenic Bladder Patients
A Phase 2/3 study testing Mirabegron in people with Urinary Bladder, Neurogenic, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 5 sites in Canada.
Trial summary
The proposed study is a randomized, double blind placebo controlled multicenter study to determine the effectiveness of mirabegron in the treatment of neurogenic bladder dysfunction. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Bladder, Neurogenic
- What is being tested?
- Mirabegron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 5 sitesCanada
- Study dates
- Jul 2014to Feb 2018
- Phase
- Phase 2/3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of traumatic or nontraumatic suprasacral spinal cord injury (SCI) or multiple sclerosis (MS, based on a neurologist assessment and/or the McDonald criteria)(28)
- Age >18 years
- Stable method of bladder management for >3months (either spontaneous or provoked voiding, or intermittent catheterization).
- Bothersome urinary symptoms (urinary frequency, urgency, or urgency incontinence based on standard ICS definitions(29)) and completed 3 day voiding diary demonstrating at least 1 episode of non-stress based urinary incontinence over the 72hr period (this may be urgency based incontinence or unaware incontinence).
- Patient is able to read and speak English
Who cannot join
- Based on Screening visit history:
- Participation in another drug or device study in the 60 days prior to the screening visit.
- Previous urologic surgery: Transurethral prostatectomy, bladder augmentation, sphincterotomy, bladder neck sling, artificial urinary sphincter, catheterizable channel, implantable electrostimulator/neuromodulator
- Current use of suprapubic catheter/foley catheter
- Unstable cardiac disease (uncontrolled hypertension, myocardial infarction, unstable angina, severe congestive heart failure (NYHA 3 or 4), ventricular arrhythmia (such as torsades de pointes), or stroke within the last 6 months)
- Clinically significant abnormal ECG
Show all 38Show fewer
- The investigator believes the patient has an increased risk of QT prolongation (based on review of the screening ECG and patients concurrent medications)
- History of significant renal dysfunction within 1 year, or serum creatinine >150umol/L at screening visit (visit 1).
- History of significant liver disease within 1 year, or serum AST/ALT >2 times upper limit of normal, GGT >3 times upper limit of normal, total bilirubin >2 times upper limit of normal at screening visit (visit 1).
- History of pelvic radiation
- History of bladder cancer
- History of a concurrent malignancy or cancer (except noninvasive skin cancer) within the last 5 years. Subjects with a history of cancer are considered eligible if the subject has undergone potentially curative therapy and the subject has been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin).
- Patient has a history of interstitial cystitis/pelvic pain syndrome
- Patient has a history of acute or chronic urinary retention within the last 3 months, and is currently not using intermittent catheters
- Patient has a history of a tachyarrhythmia
- Patient has a history of glaucoma
- Patient has a medical condition that may cause noncompliance with the study protocol
- In the opinion of the Investigator the patient has a history of significant stress urinary incontinence
- Patient has signs and symptoms of an active urinary tract infection (symptoms of dysuria, foul smelling urine, cloudy urine, increased spasticity, increased autonomic dysreflexia, self reported fever, increased incontinence, back/suprapubic pain).
- o Patient will submit urine for culture and sensitivity, undergo treatment, and will be eligible for rescreening after treatment.
- Female patient who is pregnant or breastfeeding, or plans to become pregnant.
- Male patient who is planning on fathering a child during the study or for 28 days after the last dose of study drug, or who is planning to donate sperm
- Patient refuses to provide written consent
- Patient will be unable or unwilling to complete the questionnaires and study visits
- In the opinion of the study investigator, it is not in the patient's best interest to be enrolled in this study.
- Based on medication and allergy review
- The new addition of an anticholinergic medication, or a change to anticholinergic dose, within the last 30 days, (bladder specific anticholinergics include oxybutynin, tolterodine, fesoterodine, solifenacin, darifenacin, trospium, hyoscine, oxybutynin gel or patch, atropine, benzatropine). If previously used and discontinued, these medications must have been stopped for >2 weeks
- Newly added bladder active medication (or dose change) within the last 2 months (Tamsulosin, Silodosin, Terazosin, Baclofen, Diazepam, amitriptyline, Finasteride, Dutasteride, DDAVP/desmopressin)
- Use of flecainide, propafenone, donepezil, thioridazine, tramadol, aripiprazole, desipramine, imipramine, venlafaxine or digoxin
- Intravesical onabotulinum toxin use within the last 1 year
- Intravesical oxybutynin within the last 3 months
- Patient has a previous history of treatment with mirabegron
- Patient has a known allergy to mirabegron or a previous adverse reaction to a beta 3 agonist.
- Based on physical exam
- Patient has a postvoid residual > 250mL at study enrollment after repeated tested (1 attempt to re-void to ensure complete emptying of the bladder) and is not using intermittent catheters
- Patient has a resting BP >180 mmHg systolic and/or >110 mmHg diastolic after 2 minutes of sitting quietly
- Patient has a resting heart rate >100bpm after 2 minutes of sitting quietly
- In the opinion of the study investigator, it is not in the patient's best interest to be enrolled in this study based on a clinically significant abnormality on physical exam.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Kingston General Hospital and Hotel Dieu Hospital (Queens University)
Kingston, Ontario, K7L 5G2
Western University
London, Ontario, N6A 4V2
University of Ottawa
Ottawa, Ontario, K1Y 4E9
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Rehabiliation Center, Health Sciences Center
Winnipeg, Manitoba, R3A 1M4
About this study
Official title: A Double Blind, Randomized Placebo Controlled Trial Evaluating the Urodynamic and Clinical Efficacy of Mirabegron Among Neurogenic Bladder Patients
The proposed study is a randomized, double blind placebo controlled multicenter study to determine the effectiveness of mirabegron in the treatment of neurogenic bladder dysfunction. Patients will be randomized into one of two trial arms: mirabegron 25mg for two weeks, with escalation to 50mg for the remaining 8 weeks, or matched placebo capsule for two weeks, with placebo escalation for the remaining 8 weeks. Each of these trial arms will be stratified based on whether the patient is already taking an anticholinergic medication or not. The study will treat a total of 144 patients (72 with placebo, 72 with mirabegron). The study hypothesis is that mirabegron will result in a statistically superior (increased) urodynamic bladder capacity.
The study duration is 12 weeks, with a 1-4 week run in period where no active or placebo treatment will be administered. The primary outcome measure will be based on an increase in urodynamic bladder capacity. Secondary outcome measures will be additional urodynamic parameters, urinary symptom scales, urinary quality of life indices, and voiding diary results.
Patients who are over 18 years of age with a diagnosis of multiple sclerosis (MS) or spinal cord injury (SCI) will be eligible to participate. All eligible patients will have urodynamic studies performed within 4 weeks of trial enrollment, and at the end of study (week 9-10). Adverse events and study outcomes will be assessed at predefined study time points.
- Conditions
- Urinary Bladder, Neurogenic
- Being tested
- Mirabegron, Placebo
- Keywords
- Multiple Sclerosis, Spinal Cord Injuries, mirabegron, Urodynamics
- Medical subject headings
- Urinary Bladder, Neurogenic, Multiple Sclerosis, Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirabegronDrug
Also called MYRBETRIQ
Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.
PlaceboDrug
Matched placebo capsules to the intervention arm
| Study group | Role | What they receive |
|---|---|---|
| Mirabegron | Experimental | Patients randomised to this arm start with mirabegron 25mg PO daily for two weeks, and then at 2 weeks titrate to 50mg PO daily, and maintain that dose for the duration of the study (8 additional weeks). Receives: Drug: Mirabegron |
| Placebo | Placebo comparator | Inert placebo pill, matching active treatment pill. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bladder Capacity
Urodynamic bladder capacity
Measured: 10 weeks
Secondary outcomes (12)
3 Day Voiding Diary
The 3 day voiding diary is a simple patient maintained record of fluid intake, voided volume and incontinence episodes. This will be used to assess number of episodes of urgency incontinence, urinary frequency, longest time between voids, functional capacity, and mean voided volume
Measured: 10 weeks
24hr Urinary Pad Weights
This will determine the amount of urinary incontinence that occurs over a 24hr period.
Measured: 10 weeks
Quality of Life (Bladder Specific)
The Short Form-Qualiveen is a urinary specific quality of life measure developed and studied specifically for neurogenic bladder patients; validity, reliability and responsiveness have been established.
Measured: 10 weeks
Quality of Life (Incontinence)
The I-QOL is an incontinence specific quality of life tool that has been shown to be a valid, reliable and responsive measurement among patients with neurogenic bladder dysfunction
Measured: 10 weeks
Patient Reported Outcome Measure-NBSS
The Neurogenic bladder symptom score (NBSS) is a symptom specific measure of urinary symptoms developed for patients with neurogenic bladder dysfunction with demonstrated validity and reliability. Minimum score is 0, maximum score is 74. Higher score is worse neurogenic bladder symptoms.
Measured: 10 weeks
Patient Perception of Bladder Condition
The patient perception of bladder condition is a commonly used measure in the assessment of oral medications for the treatment of overactive bladder symptoms
Measured: 10 weeks
Adverse Events
Adverse events will be monitored passively. They will be actively monitored for hypertension, tachycardia, and urinary retention.
Measured: 10 weeks
Secondary Urodynamic Characteristics: Maximum Detrusor Pressure
Measured: 10 weeks
Secondary Urodynamic Characteristics: Volume at Maximum Detrusor Pressure
Measured: 10 weeks
Secondary Urodynamic Characteristics: Bladder Sensation
Measured: 10 weeks
Secondary Urodynamic Characteristics: Bladder Compliance
Measured: 10 weeks
Secondary Urodynamic Characteristics: Volume at First Detrusor Overactivity
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2014 (estimated)
- Study startJul 2014
- Primary completionJan 2018
- Study completionFeb 2018
Why it stopped: Slow recruitment and small observed effect size
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 Urinary Bladder, NeurogenicStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Blayne Welk, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Blayne Welk, MD MSc, Principal investigator, Western University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02044510
- Sponsor's protocol ID
- SG193
- Status last verified
- Jan 2019
- First submitted
- 22 Jan 2014
- Last updated
- 5 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomized Placebo Controlled Trial Evaluating the Urodynamic and Clinical Efficacy of Mirabegron Among Neurogenic Bladder Patients
- ClinicalTrials.gov ID
- NCT02044510
- Acronym / sponsor ID
- SG193
- Conditions
- Urinary Bladder, Neurogenic
- Keywords
- Multiple Sclerosis, Spinal Cord Injuries, mirabegron, Urodynamics
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment and small observed effect size
- Enrolment
- 32 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- Jul 2014 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 24 Jan 2014 (estimated)
- Results
- Posted 7 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is a randomized, double blind placebo controlled multicenter study to determine the effectiveness of mirabegron in the treatment of neurogenic bladder dysfunction. Patients will be randomized into one of two trial arms: mirabegron 25mg for two weeks, with escalation to 50mg for the remaining 8 weeks, or matched placebo capsule for two weeks, with placebo escalation for the remaining 8 weeks. Each of these trial arms will be stratified based on whether the patient is already taking an anticholinergic medication or not. The study will treat a total of 144 patients (72 with placebo, 72 with mirabegron). The study hypothesis is that mirabegron will result in a statistically superior (increased) urodynamic bladder capacity.
The study duration is 12 weeks, with a 1-4 week run in period where no active or placebo treatment will be administered. The primary outcome measure will be based on an increase in urodynamic bladder capacity. Secondary outcome measures will be additional urodynamic parameters, urinary symptom scales, urinary quality of life indices, and voiding diary results.
Patients who are over 18 years of age with a diagnosis of multiple sclerosis (MS) or spinal cord injury (SCI) will be eligible to participate. All eligible patients will have urodynamic studies performed within 4 weeks of trial enrollment, and at the end of study (week 9-10). Adverse events and study outcomes will be assessed at predefined study time points.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mirabegron | Experimental | Drug: MirabegronPatients randomised to this arm start with mirabegron 25mg PO daily for two weeks, and then at 2 weeks titrate to 50mg PO daily, and maintain that dose for the duration of the study (8 additional weeks). |
| Placebo | Placebo comparator | Drug: PlaceboInert placebo pill, matching active treatment pill. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of traumatic or nontraumatic suprasacral spinal cord injury (SCI) or multiple sclerosis (MS, based on a neurologist assessment and/or the McDonald criteria)(28)
- Age >18 years
- Stable method of bladder management for >3months (either spontaneous or provoked voiding, or intermittent catheterization).
- Bothersome urinary symptoms (urinary frequency, urgency, or urgency incontinence based on standard ICS definitions(29)) and completed 3 day voiding diary demonstrating at least 1 episode of non-stress based urinary incontinence over the 72hr period (this may be urgency based incontinence or unaware incontinence).
- Patient is able to read and speak English
Key exclusion criteria (38 listed)
- Participation in another drug or device study in the 60 days prior to the screening visit.
- Previous urologic surgery: Transurethral prostatectomy, bladder augmentation, sphincterotomy, bladder neck sling, artificial urinary sphincter, catheterizable channel, implantable electrostimulator/neuromodulator
- Current use of suprapubic catheter/foley catheter
- Unstable cardiac disease (uncontrolled hypertension, myocardial infarction, unstable angina, severe congestive heart failure (NYHA 3 or 4), ventricular arrhythmia (such as torsades de pointes), or stroke within the last 6 months)
- Clinically significant abnormal ECG
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: MYRBETRIQMirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks. | Drug | Mirabegron |
| PlaceboMatched placebo capsules to the intervention arm | Drug | Placebo |
Primary outcome
Bladder Capacity
Time frame: 10 weeks
Urodynamic bladder capacity
12 secondary outcomes
3 Day Voiding Diary
Time frame: 10 weeks
24hr Urinary Pad Weights
Time frame: 10 weeks
Quality of Life (Bladder Specific)
Time frame: 10 weeks
Quality of Life (Incontinence)
Time frame: 10 weeks
Patient Reported Outcome Measure-NBSS
Time frame: 10 weeks
Patient Perception of Bladder Condition
Time frame: 10 weeks
Adverse Events
Time frame: 10 weeks
Secondary Urodynamic Characteristics: Maximum Detrusor Pressure
Time frame: 10 weeks
Secondary Urodynamic Characteristics: Volume at Maximum Detrusor Pressure
Time frame: 10 weeks
Secondary Urodynamic Characteristics: Bladder Sensation
Time frame: 10 weeks
Secondary Urodynamic Characteristics: Bladder Compliance
Time frame: 10 weeks
Secondary Urodynamic Characteristics: Volume at First Detrusor Overactivity
Time frame: 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Blayne Welk, MD MSc principal investigator
Western University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Mirabegron in people with Urinary Bladder, Neurogenic, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 5 sites in Canada.
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 5 inclusion and 38 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: stopped early, as of the sponsor's last update on 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Jan 2019). 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?
Bladder Capacity (time frame: 10 weeks). 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 5 Feb 2019.