Urodynamic and Clinical Efficacy of Mirabegron for Neurogenic Bladder Patients

• Sponsor: Lawson Health Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02044510
• Collaborator: (none)
• Enrollment: 32
• Locations: 5
• Arms: 2
• Actual Duration (Months): 43.1
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Bladder, Neurogenic	Drug: Mirabegron; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind, Randomized Placebo Controlled Trial Evaluating the Urodynamic and Clinical Efficacy of Mirabegron Among Neurogenic Bladder Patients
• Actual Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirabegron 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).	Drug: Mirabegron; Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.; Other Names: MYRBETRIQ
Placebo Comparator: Placebo Inert placebo pill, matching active treatment pill.	Drug: Placebo; Matched placebo capsules to the intervention arm

Outcome Measures

Primary Outcome Measures

1. Bladder Capacity [10 weeks]

   Urodynamic bladder capacity

Secondary Outcome Measures

1. 3 Day Voiding Diary [10 weeks]

   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

2. 24hr Urinary Pad Weights [10 weeks]

   This will determine the amount of urinary incontinence that occurs over a 24hr period.

3. Quality of Life (Bladder Specific) [10 weeks]

   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.

4. Quality of Life (Incontinence) [10 weeks]

   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

5. Patient Reported Outcome Measure-NBSS [10 weeks]

   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.

6. Patient Perception of Bladder Condition [10 weeks]

   The patient perception of bladder condition is a commonly used measure in the assessment of oral medications for the treatment of overactive bladder symptoms

7. Adverse Events [10 weeks]

   Adverse events will be monitored passively. They will be actively monitored for hypertension, tachycardia, and urinary retention.

8. Secondary Urodynamic Characteristics: Maximum Detrusor Pressure [10 weeks]

9. Secondary Urodynamic Characteristics: Volume at Maximum Detrusor Pressure [10 weeks]

10. Secondary Urodynamic Characteristics: Bladder Sensation [10 weeks]

11. Secondary Urodynamic Characteristics: Bladder Compliance [10 weeks]

12. Secondary Urodynamic Characteristics: Volume at First Detrusor Overactivity [10 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• 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

Exclusion criteria:

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

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rehabiliation Center, Health Sciences Center	Winnipeg	Manitoba	Canada	R3A 1M4
2	Kingston General Hospital and Hotel Dieu Hospital (Queens University)	Kingston	Ontario	Canada	K7L 5G2
3	Western University	London	Ontario	Canada	N6A 4V2
4	University of Ottawa	Ottawa	Ontario	Canada	K1Y 4E9
5	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8

Sponsors and Collaborators

• Lawson Health Research Institute

Investigators

• Principal Investigator: Blayne Welk, MD MSc, Western University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 30, 2014
• Informed Consent Form - Sep 30, 2014

More Information

Publications

None provided.

• Responsible Party: Blayne Welk, Principal Investigator, Lawson Health Research Institute
• ClinicalTrials.gov Identifier: NCT02044510
• Other Study ID Numbers: SG193
• First Posted: Jan 24, 2014
• Last Update Posted: Feb 5, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Blayne Welk, Principal Investigator, Lawson Health Research Institute: Multiple Sclerosis; Spinal Cord Injuries; mirabegron; Urodynamics
• Additional relevant MeSH terms: Urinary Bladder, Neurogenic; Mirabegron

Study Results

Participant Flow

Arm/Group Title	Mirabegron	Placebo
Arm/Group Description	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). Mirabegron: Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.	Inert placebo pill, matching active treatment pill. Placebo: Matched placebo capsules to the intervention arm
Period Title: Overall Study
STARTED	16	16
COMPLETED	15	14
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Mirabegron	Placebo	Total
Arm/Group Description	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). Mirabegron: Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.	Inert placebo pill, matching active treatment pill. Placebo: Matched placebo capsules to the intervention arm	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 12.5%	1 6.3%	3 9.4%
>=65 years	14 87.5%	15 93.8%	29 90.6%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	50	56	54
Sex: Female, Male (Count of Participants)
Female	8 50%	7 43.8%	15 46.9%
Male	8 50%	9 56.3%	17 53.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Number of participants with a Spinal cord injury (SCI), n (Count of Participants)
Count of Participants [Participants]	9 56.3%	10 62.5%	19 59.4%
Number of participants with Mulitple sclerosis (MS), n (Count of Participants)
Count of Participants [Participants]	7 43.8%	6 37.5%	13 40.6%

Outcome Measures

1. Primary Outcome

Title	Bladder Capacity
Description	Urodynamic bladder capacity
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mirabegron	Placebo
Arm/Group Description	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). Mirabegron: Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.	Inert placebo pill, matching active treatment pill. Placebo: Matched placebo capsules to the intervention arm
Measure Participants	16	16
Least Squares Mean (95% Confidence Interval) [mL]	305	369

2. Secondary Outcome

Title	3 Day Voiding Diary
Description	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
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	24hr Urinary Pad Weights
Description	This will determine the amount of urinary incontinence that occurs over a 24hr period.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Quality of Life (Bladder Specific)
Description	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.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Quality of Life (Incontinence)
Description	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
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Patient Reported Outcome Measure-NBSS
Description	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.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Patient Perception of Bladder Condition
Description	The patient perception of bladder condition is a commonly used measure in the assessment of oral medications for the treatment of overactive bladder symptoms
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Adverse Events
Description	Adverse events will be monitored passively. They will be actively monitored for hypertension, tachycardia, and urinary retention.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Secondary Urodynamic Characteristics: Maximum Detrusor Pressure
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Secondary Urodynamic Characteristics: Volume at Maximum Detrusor Pressure
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Secondary Urodynamic Characteristics: Bladder Sensation
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Secondary Urodynamic Characteristics: Bladder Compliance
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Secondary Urodynamic Characteristics: Volume at First Detrusor Overactivity
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	10 Weeks
Arm/Group Title	Mirabegron		Placebo
Arm/Group Description	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). Mirabegron: Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.		Inert placebo pill, matching active treatment pill. Placebo: Matched placebo capsules to the intervention arm
All Cause Mortality
	Mirabegron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Mirabegron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Mirabegron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.