Myrbetriq™ (Mirabegron) to Reduce Pain and Discomfort Following Ureteral Stent Placement

Study Overview
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Brief Summary
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The objective of this pilot study is to assess whether Myrbetriq™ will improve post-operative ureteral pain and discomfort, reduce bladder storage symptoms and increase quality of life following ureteral stenting.

Official Title
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Myrbetriq™ (Mirabegron) to Reduce Pain and Discomfort Following Ureteral Stent Placement

Conditions
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Urinary Bladder, Overactive, Pain, Lower Urinary Tract Symptoms

Intervention / Treatment
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* Drug: Mirabegron
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18. Subject scheduled to undergo a ureteral stent placement for ureteral obstruction or post- ureteroscopy procedure. Otherwise healthy subjects who are able and willing to participate in the study. None of the planned interventions are documented in the labeled contraindications, warnings and precautions of the study drug. Exclusion Criteria: Does NOT give consent. Subject is using prohibited medications which cannot be stopped safely at the screening visit. Subject is excluded if using restricted medications not meeting protocol-specified criteria: (i) Phytotherapy for BPH or a 5-alpha reductase inhibitor within 3 months, with persistent urinary symptoms and AUASS more than 7. (ii) Taken an oral alpha agonist, anticholinergic or cholinergic medication within 5 days of the first screening visit with the following exception(s): a singular dose given in ER or on the hospital floor prior to procedure, topical anticholinergic eye drops used for glaucoma or inhaled anti-cholinergic used for COPD. (iii) Taken tricyclic antidepressants within 2 weeks of the first screening visit. (iv) Taken an estrogen, androgen, or any drug producing androgen suppression, or anabolic steroids within 3 months with the following exceptions: any topical creams for local treatment. Post void residual volume > 350 mL. Female subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential is sexually active and not practicing a highly reliable method of birth control. Subject has known neurogenic bladder. Subject with uncontrolled chronic pain problems or on chronic pain medications. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator (for female subjects confirmed by a cough provocation test). Subject has an indwelling catheter or practices intermittent self-catheterization. Known primary neurologic conditions such as multiple sclerosis, Parkinson's disease, diabetic neuropathy or any neurological diseases known to affect bladder function. Subject has evidence of a symptomatic active urinary tract infection, chronic inflammation such as interstitial cystitis, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs, or bladder stones (which can be located in different anatomical location and can cause LUTS similar to bladder infection and pain related to their location in the bladder which could mask the treatment effect). Subject who is currently under active treatment with botulinum toxin (and all other bladder paralytics) intravesically. Subject has moderate to severe hepatic impairment [ALT (SGPT) or AST (SGOT) value greater than 3 times the upper limit of normal in the clinical center lab; confirmed on a second measurement]. Subject has severe renal impairment or End Stage Renal disease (i.e., creatinine greater than 2.0 mg/dl). Subject has severe uncontrolled hypertension (defined as systolic blood pressure ≥180mmHg and /or diastolic pressure ≥ 110mmHg). Subject has a clinically significant abnormal ECG in their chart or has a known history of QT prolongation or currently taking medication known to prolong the QT interval. Any patient taking Digoxin. Subject has a known or suspected hypersensitivity to Mirabegron or any of the inactive ingredients. Subject has a concurrent genitourinary malignancy, or active cancer (except noninvasive skin cancer) within the last 5 years prior to screening. Men with a history of prostate cancer regardless of curability are not eligible. Subject has been treated with an experimental device within 30 days or received an experimental agent within the longer of 30 days or five half-lives. Unable to follow protocol directions due to organic brain or psychiatric disease. Intra-operative complications that require hospital admissions. History of alcoholism or any other substance abuse, which, in the opinion of the investigator, would affect compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>after stent placement, patient will be given Mirabegron 50 mg, PO, once daily, for 2 weeks | Drug: Mirabegron<br> <br> * Other names: Myrbetriq;|
| Placebo Comparator: Placebo Arm<br>after stent placement, patient will be given placebo PO, once daily, for 2 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | Incontinence symptom severity index is a self-assessment instrument for voiding symptom severity. It assesses 8 symptom domains: emptying, urgency, urge incontinence, nocturia, daytime frequency, stress incontinence, leakage with physical activity, and pad use. absent/mild (0-6), moderate (7-16), severe (>16). | 2 weeks | 
| Improvement From Baseline in the Number Micturitions Per 24 Hours in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | Only seven patients were enrolled and two of them withdrew after the first dose. Patients did not provide baseline micturitions. They were given a voiding diary after randomization to be conducted prior to their next follow-up visit. Therefore, improvement in the number of micturitions at 2 weeks cannot be analyzed from baseline | 2 weeks | 
| Improvement From Baseline in the Number of Incontinence Episodes in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | Only seven patients were enrolled and two of them withdrew after the first dose. Patients did not provide baseline number of incontinence episodes. They were given a voiding diary after randomization to be conducted pror to their next follow-up visit. Therefore, improvement in the number of incontinence episodes at 2 weeks cannot be analyzed from baseline. | 2 weeks | 
| Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | Only seven patients were enrolled and two of them withdrew after the first dose. Therefore, we are only left with 5 patients completing the study. Incontinence symptom severity index is a self-assessment instrument for voiding symptom severity. It assesses 8 symptom domains: emptying, urgency, urge incontinence, nocturia, daytime frequency, stress incontinence, leakage with physical activity, and pad use. absent/mild (0-6), moderate (7-16), severe (>16). . | 1 week | 
| Improvement From Baseline in the Number Micturitions Per 24 Hours in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | Only seven patients were enrolled and two of them withdrew after the first dose. Therefore, we are only left with 5 patients at the one week follow-up. Patients did not provide baseline micturitions. They were given a voiding diary after randomization to be conducted prior to their next follow-up visit. Therefore, improvement in the number of micturitions at 1 week cannot be analyzed from baseline | 1 week | 
| Improvement From Baseline in the Number of Incontinence Episodes in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | Only seven patients were enrolled and two of them withdrew after the first dose. Therefore, we are only left with 5 patients at the one week follow-up. Patients did not provide baseline number of incontinence episodes. They were given a voiding diary after randomization to be conducted pror to their next follow-up visit. Therefore, improvement in the number of incontinence episodes at 1 week cannot be analyzed from baseline. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Pain and Discomfort Perception Using a 10 Point Visual Analog Scale for Pain Assessment (VAS) at the 1 and 2 Week Follow-up. | Only seven patients were enrolled and two of them withdrew after the first dose. Therefore, we are only left with 5 patients completing the study. Visual analog scale is from 1-10 (10 being the worse possible pain). | 1 week, 2 weeks | 
| Improvement From Baseline on the Patient Global Impression of Severity (PGI-S) at the 2 Week Follow-up. | Only seven patients were enrolled and two of them withdrew after the fist dose. Therefore, we are only left with 5 patients completing the study. PGI-S is a four item questionnaire asking for patient enumeration of their urinary symptoms when compared to symptoms prior to surgery (1= normal, 2=mild, 3=moderate, 4=severe) | 2 weeks | 
| Reduction in Pain Medicine Intake at the 2 Week Follow-up | This outcome measure will be listed in 1) mean number of days that pain medications were taken | 2 weeks | 
| Reduction in Pain Medicine Intake at the 2 Week Follow-up | This outcome measure will be listed in mean number of times per day that pain medication was taken | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ureteral Stents, Pain and Discomfort, Bladder Storage Symptoms