Lower Urinary Tract Symptoms, Pain, Urinary Bladder, Overactive
Conditions
Keywords
Ureteral Stents, Pain and Discomfort, Bladder Storage Symptoms
Brief summary
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.
Interventions
DRUGMirabegron
DRUGPlacebo
Sponsors
Astellas Scientific & Medical Affairs, Inc.
Sisters of the Third Order of St. Francis
Southern Illinois University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18. 2. Subject scheduled to undergo a ureteral stent placement for ureteral obstruction or post- ureteroscopy procedure. 3. Otherwise healthy subjects who are able and willing to participate in the study. 4. None of the planned interventions are documented in the labeled contraindications, warnings and precautions of the study drug.
Exclusion criteria
1. Does NOT give consent. 2. 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. 3. Post void residual volume \> 350 mL. 4. 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. 5. Subject has known neurogenic bladder. 6. Subject with uncontrolled chronic pain problems or on chronic pain medications. 7. 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). 8. Subject has an indwelling catheter or practices intermittent self-catheterization. 9. Known primary neurologic conditions such as multiple sclerosis, Parkinson's disease, diabetic neuropathy or any neurological diseases known to affect bladder function. 10. 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). 11. Subject who is currently under active treatment with botulinum toxin (and all other bladder paralytics) intravesically. 12. Subject has moderate to severe hepatic impairment \[ALT (SGPT) or AST (SGOT) value greater than 3 times the upper limit of normal in the clinical center lab; confirmed on a second measurement\]. 13. Subject has severe renal impairment or End Stage Renal disease (i.e., creatinine greater than 2.0 mg/dl). 14. Subject has severe uncontrolled hypertension (defined as systolic blood pressure ≥180mmHg and /or diastolic pressure ≥ 110mmHg). 15. 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. 16. Subject has a known or suspected hypersensitivity to Mirabegron or any of the inactive ingredients. 17. 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. 18. 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. 19. Unable to follow protocol directions due to organic brain or psychiatric disease. 20. Intra-operative complications that require hospital admissions. 21. History of alcoholism or any other substance abuse, which, in the opinion of the investigator, would affect compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement From Baseline in the Number of Incontinence Episodes in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | 1 week | 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. |
| Improvement From Baseline in the Number of Incontinence Episodes in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | 2 weeks | 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. |
| Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | 1 week | 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). . |
| Improvement From Baseline in the Number Micturitions Per 24 Hours in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | 1 week | 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 |
| Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | 2 weeks | 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). |
| Improvement From Baseline in the Number Micturitions Per 24 Hours in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | 2 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement From Baseline on the Patient Global Impression of Severity (PGI-S) at the 2 Week Follow-up. | 2 weeks | 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) |
| Reduction in Pain Medicine Intake at the 2 Week Follow-up | 2 weeks | This outcome measure will be listed in 1) mean number of days that pain medications were taken |
| 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. | 1 week, 2 weeks | 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). |
Countries
United States
Participant flow
Pre-assignment details
We consented 11 patients. Two were screen fails (SF) after consenting but prior to randomization. Two patients were early withdrawls (EW) prior to enrollment when their surgeries were moved to a non-study hospital. Of the 11 total consented, 4 dropped out resulting in a total of 7 being assigned to a treatment arm. One of the SF patients provided baseline quesionnaire date (which has been updated), the other SF and both EW did not provide any baseline information.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm after stent placement, patient will be given Mirabegron 50 mg, PO, once daily, for 2 weeks
Mirabegron | 4 |
| Placebo Arm after stent placement, patient will be given placebo PO, once daily, for 2 weeks
Placebo | 3 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | pt developed hives | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment Arm | Placebo Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 6 Participants |
| American Urological Association Symptom Score (AUASS) | 18.75 units on a scale | 8.67 units on a scale | 14.42 units on a scale |
| Incontinence Symptom Severity Index (ISSI) | 13 units on a scale | 4.67 units on a scale | 9.43 units on a scale |
| Patient Global Impression of Severity (PGI-S) Questionnaire | 3 units on a scale | 2 units on a scale | 2.67 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
| Visual Analog Scale (VAS) | 4 units on a scale | 0.67 units on a scale | 2.57 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 1 / 4 | 1 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
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). .
Time frame: 1 week
Population: Study was terminated due to insufficient rate of accrual. Therefore, we are only left with 5 patients completing the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Arm | Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | 10 score on a scale |
| Placebo Arm | Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 1 Week Follow-up Compared to Placebo Group. | 6.67 score on a scale |
Primary
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).
Time frame: 2 weeks
Population: Study was terminated due to insufficient rate of accrual. Only seven patients were assigned to treatment/placebo arms and two of them (both in treatment) withdrew after the first dose. Therefore, we are only left with 5 patients completing the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Arm | Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | 9.5 score on a scale |
| Placebo Arm | Improvement From Baseline in the Incontinence Symptom Severity Index (ISSI) in the Myrbetriq™ Group at the 2 Week Follow-up Compared to Placebo Group. | 8 score on a scale |
Primary
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
Time frame: 1 week
Population: Patients did not provide baseline micturitions so cannot do analysis of improvemet of baseline to 1 week f/u.
Primary
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
Time frame: 2 weeks
Population: Study was terminated due to insufficient rate of accrual. Only seven patients were assigned to treatment/placebo arms and two of them (both in treatment) withdrew after the first dose. Therefore, we are only left with 5 patients completing the study. Patients did not provide baseline micturitions so cannot do analysis of improvemet of baseline to 2 week f/u.
Primary
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.
Time frame: 1 week
Population: Study was terminated due to insufficient rate of accrual. Patient did not provide baseline number of incidence so cannot do analysis of improvement of baseline to 1 week follow-up.
Primary
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.
Time frame: 2 weeks
Population: Study was terminated due to insufficient rate of accrual. Only seven patients were assigned to treatment/placebo arms and two of them (both in treatment) withdrew after the first dose. Therefore, we are only left with 5 patients completing the study. Patient did not provide baseline number of incidence so cannot do analysis of improvement of baseline to 2 week follow-up.
Secondary
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)
Time frame: 2 weeks
Population: Study was terminated due to insufficient rate of accrual. 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Arm | Improvement From Baseline on the Patient Global Impression of Severity (PGI-S) at the 2 Week Follow-up. | 2.5 score on a scale |
| Placebo Arm | Improvement From Baseline on the Patient Global Impression of Severity (PGI-S) at the 2 Week Follow-up. | 2 score on a scale |
Secondary
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).
Time frame: 1 week, 2 weeks
Population: Study was terminated due to insufficient rate of accrual. Only seven patients were assigned to treatment/placebo arms and two of them (both in treatment) withdrew after the first dose. Therefore, we are only left with 5 patients completing the study.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Arm | 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. | 1 week follow/up | 4 score on a scale |
| Treatment Arm | 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. | 2 week follow/up | 4.5 score on a scale |
| Placebo Arm | 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. | 1 week follow/up | 2.67 score on a scale |
| Placebo Arm | 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. | 2 week follow/up | 1.33 score on a scale |
Secondary
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
Time frame: 2 weeks
Population: Study was terminated due to insufficient rate of accrual. Only seven patients were enrolled and two of them withdrew after the first dose. Therefore, 5 patients completed study. We are including the two early withdrawal patients in this population analysis because they did provide the pain medication log prior to withdrawal.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Arm | Reduction in Pain Medicine Intake at the 2 Week Follow-up | 5 days |
| Placebo Arm | Reduction in Pain Medicine Intake at the 2 Week Follow-up | 7.67 days |
Secondary
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
Time frame: 2 weeks
Population: Study was terminated due to insufficient rate of accrual. Only seven patients were enrolled and two of them withdrew after the first dose. There 5 patients completed study. We are including the two early withdrawal patients because they did provide the pain medication log prior to withdrawal.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Arm | Reduction in Pain Medicine Intake at the 2 Week Follow-up | 2.22 # times per day pain medication taken |
| Placebo Arm | Reduction in Pain Medicine Intake at the 2 Week Follow-up | 1.4 # times per day pain medication taken |