Flank Pain, Ureteral Obstruction
Conditions
Keywords
Medical expulsive therapy, ureteral stone, stent pain
Brief summary
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
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.
Interventions
DRUGMirabegron
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.
OTHERPlacebo
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.
Sponsors
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneous Stone Passage Using Fisher's Exact Test | 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Pain Levels Between Treatment Groups Using the Wong-Baker Pain Rating Scale | 2 months | 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. |
Countries
United States
Participant flow
Pre-assignment details
33 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 - Active Mirabegron 50 mg orally once every 24 hours starting immediately
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. | 17 |
| Arm 2 - Placebo Placebo orally once every 24 hours starting immediately
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. | 16 |
| Total | 33 |
Baseline characteristics
| Characteristic | Arm 1 - Active | Arm 2 - Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 11 | 40.8 years STANDARD_DEVIATION 9.1 | 40.45 years STANDARD_DEVIATION 20.1 |
| BMP Calcium | 1.1 mmol/L STANDARD_DEVIATION 0.1 | 1.2 mmol/L STANDARD_DEVIATION 0.1 | 1.15 mmol/L STANDARD_DEVIATION 0.2 |
| BMP Creatinine | 1 mg/dl STANDARD_DEVIATION 0.2 | .9 mg/dl STANDARD_DEVIATION 0.2 | 0.95 mg/dl STANDARD_DEVIATION 0.4 |
| BMP Potassium | 4 mmol/L STANDARD_DEVIATION 0.4 | 3.8 mmol/L STANDARD_DEVIATION 0.4 | 3.9 mmol/L STANDARD_DEVIATION 0.8 |
| CBC Hgb | 10.7 grams/dL STANDARD_DEVIATION 2.5 | 11.1 grams/dL STANDARD_DEVIATION 2.6 | 10.9 grams/dL STANDARD_DEVIATION 5.1 |
| CBC Platelets | 15.1 10^10 platelets per liter STANDARD_DEVIATION 1.6 | 13.6 10^10 platelets per liter STANDARD_DEVIATION 1.3 | 14.35 10^10 platelets per liter STANDARD_DEVIATION 2.9 |
| CBC WBC | 10.7 10^9 cells/L STANDARD_DEVIATION 2.5 | 11.1 10^9 cells/L STANDARD_DEVIATION 2.6 | 10.9 10^9 cells/L STANDARD_DEVIATION 5.1 |
| Gender Female | 3 Participants | 6 Participants | 9 Participants |
| Gender Male | 14 Participants | 10 Participants | 24 Participants |
| Previous Stone No | 11 count of participants | 5 count of participants | 8 count of participants |
| Previous Stone Yes | 6 count of participants | 11 count of participants | 8.5 count of participants |
| Race/Ethnicity, Customized Black/African | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants | 15 Participants | 30 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 16 Participants | 32 Participants |
| Region of Enrollment United States | 17 Participants | 16 Participants | 33 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 10 Participants | 24 Participants |
| Stone Location Lower | 14 Participants | 5 Participants | 19 Participants |
| Stone Location Upper | 3 Participants | 11 Participants | 14 Participants |
| Stone Size | 5.5 mm STANDARD_DEVIATION 1.5 | 5.4 mm STANDARD_DEVIATION 1.6 | 5.45 mm STANDARD_DEVIATION 3.1 |
| UA RBC | 20 RBC/HPF STANDARD_DEVIATION 4 | 19 RBC/HPF STANDARD_DEVIATION 5 | 19.5 RBC/HPF STANDARD_DEVIATION 11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 0 / 16 | 0 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
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.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 - Active | Spontaneous Stone Passage Using Fisher's Exact Test | 8 Participants |
| Arm 2 - Placebo | Spontaneous Stone Passage Using Fisher's Exact Test | 5 Participants |
Secondary
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.
Time frame: 2 months
Population: Comparisons between arms were calculated with ttest, Wilcoxon rank sum, and Fisher's exact test. Regression assessed odds of stone passageby 30 day visit by treatment arm. Time-to-stone pass was analyzed using Kaplan-Meier curves, log rank test,Cox proportional hazards regression. Patients who didn't pass stone were censored at last follow-up date. Wong-Baker Pain Rating Scale has zero to ten range. Zero represents no pain and ten represents worst.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 - Active | Comparison of Pain Levels Between Treatment Groups Using the Wong-Baker Pain Rating Scale | 0.21 units on a scale |
| Arm 2 - Placebo | Comparison of Pain Levels Between Treatment Groups Using the Wong-Baker Pain Rating Scale | 0.19 units on a scale |