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

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)

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.

Study Overview

• Status: Completed
• Conditions: Ureteral Obstruction; Flank Pain
• Intervention / Treatment: Drug: Mirabegron; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Positive nitrites
  2. White blood cell count greater than 15/hpf (high powered field)
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1 - Active; Mirabegron 50 mg orally once every 24 hours starting immediately	Drug: Mirabegron; 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.; Other Names: Myrbetriq
Placebo Comparator: Arm 2 - Placebo; Placebo orally once every 24 hours starting immediately	Other: Placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Wesley A. Mayer, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2017
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Medical expulsive therapy; stent pain; ureteral stone
• Additional Relevant MeSH Terms: Urologic Diseases; Pain; Neurologic Manifestations; Pathological Conditions, Anatomical; Ureteral Diseases; Urolithiasis; Urinary Calculi; Calculi; Ureteral Calculi; Ureterolithiasis; Ureteral Obstruction; Flank Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron
• Other Study ID Numbers: H-38959

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be published in a aggregate format after completion of study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No