Mirabegron as Medical Expulsive Therapy (MET) for Ureteral Stones and Ureteral Stent Pain

Study Overview
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Brief Summary
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The study will be a prospective randomized double-blind placebo-controlled trial of mirabegron for medical expulsive therapy (MET) in patients with a CT (Computed Tomography) scan-proven ureteral stone between 4 to 10 mm undergoing expectant management.

Detailed Description
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The study will be a prospective randomized double-blind placebo-controlled trial of mirabegron for medical expulsive therapy (MET) in patients with a CT scan-proven ureteral stone between 4 to 10 mm undergoing expectant management. Subjects will be distributed at a 1:1 ratio between the control and treatment groups. The treatment group will receive mirabegron and the control groups will receive a placebo. Both groups will receive analgesics and hydration will be recommended. All subjects will then be followed for 30 days to determine the proportion of subjects with spontaneous passage. Patients will record narcotic usage and pain scores during this time. If there is stone persistence in the ureter based on imaging (CT scan of the abdomen and pelvis versus renal ultrasound plus KUB), then the patient will undergo ureteroscopy with stent placement. In these patients, treatment will continue while the stent is in place and patients will fill out a validated questionnaire regarding stent pain.

Official Title
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A Double Blind Placebo Control Trial of Mirabegron for Medical Expulsive Therapy and to Manage Stent Pain for Ureteral Stones(Protocol # 01-16-20-02)

Conditions
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Ureteral Obstruction, Flank Pain

Intervention / Treatment
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* Drug: Mirabegron
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single unilateral ureteral calculus 4 to 10 mm visible on CT scan within the ureter Serum creatinine within normal range Ability to tolerate oral fluids and oral pain medication Able to make informed medical decisions regarding consent Willingness to follow-up in the Urology Clinic in approximately 30 day Willing to undergo ureteroscopic extraction should the stone not pass in this time period Exclusion Criteria: Adults unable to consent Age less than 18 Multiple stones Solitary kidney Horseshoe kidney On immunosuppressant therapy On digoxin Uncontrolled hypertension (Systolic blood pressure > 170, diastolic blood pressure > 110) History of ureteral surgery or previous endoscopic procedure Allergy to mirabegron Current calcium antagonist or corticosteroid or tamsulosin usage Patients already taking a beta-adrenergic agonist medication Renal insufficiency [Glomerular Filtration Rate (GFR) less than 60] Patients with Childs B and C liver failure Signs of infection i. Temperature greater than 38 degrees Celsius ii. Urinalysis with any of the following positive: Positive nitrites White blood cell count greater than 15/hpf (high powered field) Positive urine culture [defined as a single isolated bacterial species population of greater than 100,000 Colony Forming Units (CFU)] Patients with chronic pain already undergoing treatment with narcotic medications Pregnant women and nursing mothers Prisoners No working phone number

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 - Active<br>Mirabegron 50 mg orally once every 24 hours starting immediately | Drug: Mirabegron<br>* Randomized 1:1 ratio using a randomized block design, stratified by stone size (≤5 mm versus >5 mm) and location (upper versus lower ureter). The randomization will be implemented through a database with software designed by the Director of Research Informatics at the Baylor College of Medicine's Dan Duncan Institute of Clinical and Translational Research. It will be a HIPPA-compliant secure database accessible via internet.<br>* Other names: Myrbetriq;|
| Placebo Comparator: Arm 2 - Placebo<br>Placebo orally once every 24 hours starting immediately | Other: Placebo<br>* Randomized 1:1 ratio using a randomized block design, stratified by stone size (≤5 mm versus >5 mm) and location (upper versus lower ureter). The randomization will be implemented through a database with software designed by the Director of Research Informatics at the Baylor College of Medicine's Dan Duncan Institute of Clinical and Translational Research. It will be a HIPPA-compliant secure database accessible via internet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous Stone Passage Using Fisher's Exact Test | The primary outcome was stone passage rate at 30-days defined by either imaging (CT or Renal Ultrasound/KUB) or identification of stone using a straining device. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Pain Levels Between Treatment Groups Using the Wong-Baker Pain Rating Scale | Pain measures between treatment groups will be measured daily for each patient by using the Wong-Baker Pain Rating Scale. The Questionnaire will be observed in patients who require surgical intervention, and will be observed during study visit. A general linear model will be used to compare Wong-Baker pain scores between the treated and placebo groups. The model will also be used to explore associations between pain scores and demographic or clinical characteristics adjusting for treatment group. | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Medical expulsive therapy, ureteral stone, stent pain