Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03558919 |
| Other study ID # |
Mirabegron |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2017 |
| Est. completion date |
December 30, 2017 |
Study information
| Verified date |
June 2018 |
| Source |
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Overactive bladder (OAB) is a chronic symptom complex that can substantially impair quality
of life. Pharmacological management using antimuscarinics agent remain the mainstay of
therapy and effectively reduce OAB symptoms. However, despite the proven efficacy of such
agents, their tolerability may be limited by adverse events, mostly dry mouth. In fact these
adverse events often lead to poor compliance and discontinuation of therapy.The
β3-adrenoceptor agonist, mirabegron, which acts via a different mechanism of action to
antimuscarinics, could potentially improve the efficacy/ tolerability balance over current
standard of care in the management of OAB.β3-adrenoceptor agonists relax detrusor smooth
muscle during the bladder storage phase and increase bladder capacity without negatively
affecting voiding parameters. Different study has report efficacy and safety of mirabegron
but not done in our country.
Investigators will evaluate the efficacy and safety of mirabegron comparison with solifenacin
succinate in the treatment of overactive bladder.This is a hospital based prospective
randomized controlled clinical trial will be conducted from July 2016 to November 2017 in the
department of urology, Bangabandhu Sheikh Mujib Medical University (BSMMU). Among the patient
with overactive bladder who will visit to Urology outpatient department (OPD) of BSSMU, 56
patient who will fulfil the inclusion criteria will be selected. Selected patients will be
evaluated by history, physical examinations and investigation like routine urine analysis &
culture, serum creatinine, random blood sugar, X-ray kidney, ureter & bladder (KUB)
region,ultrasonogram (USG) of KUB region with maximum cystometric capacity (MCC) &
post-viodal residue (PVR). After taking informed consent, selected 82 patient will be
randomly divided in to experimental group and control group, each containing 41 patients. All
patients will be entered into one week run-in period, when they will instructed to stop any
drug including any anti-cholinergics, if they are getting it before. Patient will be supplied
with a Bengali version micturition diary from and instructed to complete a 3 day voiding
diary. Average of three day will be calculated for 24 hours.Overactive symptom score will be
calculated by interviewing the patient for urinary symptom for last 7 days. Experimental
group will receive Mirabegron 25mg and control group will receive solifenacin succinate 5 mg
all are at night for 12 weeks. Patients in both group will be regularly followed up 12 weeks
at 4 weeks interval.Patient will be supplied with a Bengali version micturition diary from
and instructed to complete a 3 day voiding diary in each follow up schedule visit at the end
of 4, 8 and 12 weeks. Overactive symptom score will be calculated by interviewing the patient
for urinary symptom for last 7 days in each visit.Patient will be evaluated for any adverse
effects during the medication. Data will be collected, complied, computed and appropriate
statistical analysis will be done as per objectives
Description:
Introduction:
Overactive bladder syndrome (OAB) is defined by the International Continence Society as
urinary urgency, with or without urgency incontinence, usually with increased daytime
frequency and nocturia in the absence of proven infection or any other pathology.
Epidemiological data suggest that OAB syndrome is present in about 10.7% of all adult men and
women, although prevalence rates increase with aging in both sexes. The prevalence of OAB
worldwide is estimated as being greater in women versus men (11.6% vs 9.7%, respectively) It
is a chronic symptom complex that can substantially impair quality of life. The prevalence of
lower urinary tract symptom (LUTS), OAB and urgency urinary incontinence is substantial,
affecting both women and men, and resulting in considerable morbidity, personal cost and
health economic burden.
Initial management uses conservative measures, such as fluid advice and bladder training.
Antimuscarinic drugs (eg. Solifenacin succinate) are still the mainstay of oral
pharmacological treatment for OAB, relaxing the detrusor muscle and reducing sensory symptoms
during the storage phase of the micturition cycle by inhibiting muscarinic receptor subtypes,
M2 and M3. Both subtypes are expressed in multiple tissues, increasing the risk of
bothersome, anticholinergic adverse events (AEs) such as dry mouth, which along with lack of
efficacy, is the most frequently cited reason for discontinuation of antimuscarinic
treatment.
Recent advances in the understanding of OAB have identified three β-adrenoceptor sub-types
β1, β2 and β3, in the detrusor muscle and urothelium .The β3-adrenoceptor is the predominant
β-receptor subtype in the human urinary bladder.
β3-adrenoceptor agonists relax detrusor smooth muscle during the bladder storage phase and
increase bladder capacity without negatively affecting voiding parameters, including maximum
urinary flow rate (Qmax), detrusor pressure at Qmax (PdetQmax), and residual volume.
The β3-adrenoceptor agonist, mirabegron, which acts via a different mechanism of action to
antimuscarinics, could potentially improve the efficacy/ tolerability balance over current
standard of care in the management of OAB. In four 12-week phase III studies mirabegron
consistently demonstrated superiority over placebo with respect to reductions in incontinence
episodes and micturition frequency.
The main adverse effects of mirabegron is hypertension, nasopharyngitis, headache and urinary
tract infection. Dry mouth and constipation are similar as placebo but lower than the
solifenacin succinate.
There were several studies observe mirabegron is effective as well as well tolerable in OAB.
There was a single comparative study between mirabegron & solifenacin shows non inferiority
of mirabegron than solifenacin. But all the study done by industrial sponsored. In
Bangladesh, no such study was performed previously. So it is time demanding to conduct a
comparative study between the safety and efficacy of mirabegron & solifenacin in patient with
overactive bladder in this country.
This new drug β3 adrenoceptor agonist mirabegron is available as 25mg once daily formulation
in the treatment of OAB in Bangladesh.
This study has been designed to see the efficacy and safety of mirabegron comparison with
solifenacin succinate in the treatment of overactive bladder without industrial support.
Hypothesis Null hypothesis (H0): There is no difference in efficacy and safety of mirabegron
and solifenacin succinate for treatment of overactive bladder.
Alternate hypothesis (HA):The efficacy and safety of mirabegron is superior to solifenacin
succinate for treatment of overactive bladder.
Objective General objective To compare the therapeutic efficacy and safety of mirabegron
comparison with solifenacin succinate in the treatment of overactive bladder.
Specific objective
- Compare the overactive bladder symptom score (OABSS) between both treatment group.
- To find out the micturition frequency and nocturia of the both treatment group and
compare between them.
- To find out the urgency and urge incontinence of the both treatment group and compare
between them.
- To compare the adverse effects of mirabegron and solifenacin succinate to treat
overactive bladder.
Methodology:
Type of study: Hospital based prospective randomized controlled clinical trial.
Study period: July 2016 to November 2017.
Place of study: Department of Urology, Bangabandhu Sheikh Mujib Medical University(BSMMU),
Dhaka, Bangladesh.
Study subject:
Men and women age at least 18 years with persistent overactive bladder (OAB) symptoms for 3
months or more and will be treated as out patients who attended in the out patient department
of Urology, BSMMU, Dhaka, will be enrolled in this study.
Sampling technique:
Purposive sampling technique will be applied to collect the sample for this study.
The patent will come with the symptoms of OAB in outpatient department of urology of BSMMU
hospital will be selected as per inclusion and exclusion criteria for the present study.
After written informed consent, a total 82 will be recruit and divided into two groups by
randomization. First participant will selected by lottery method then rest of the
participants will be enrolled alternatively dividing into two groups.
Methods This randomized clinical will be conduct in the department of urology, BSMMU, Dhaka
after receiving approval from Institutional Review Board (IRB). The study population will
select on the basis of selection criteria from the patient attended in the out patient
department of Urology, BSMMU, Dhaka.
Evaluation of patients before drug therapy:
Study commence with the initial visit during which a complete medical history was taken along
with a physical examination with special attention to uro-genital and nervous system. Digital
rectal examination (DRE) will be done to exclude any suspected pelvic pathology causing
bladder outlet obstruction (BOO) and neuropathic bladder by assessing perianal sensation and
anal tone, bulbocavernous reflex and other relevant neurological examination.
Laboratory screening for Hb% and clinical chemistry (blood sugar, serum creatinine) and urine
routine examination and culture and sensitivity will be done to exclude urinary tract
infection (UTI). Ultrasonography of the KUB region with MCC and PVR will be done to exclude
any obstructive uropathy. Plain x-ray KUB will be done to exclude urinary stone disease and
any lesion in vertebral column.
After complete of baseline clinical evaluation and investigation, those meting the inclusion
criteria will be selected for the present study.
A written informed consent will be taken from all the study subject without exploiting any of
their weakness. For the study a well-informed, voluntary, signed written consent will be
taken in an understandable local language from the patient after convincing them that their
privacy and confidentiality will be safeguard.
A data sheet will be complete for each patient included particulars of the patient, relevant
history, examination finding and relevant baseline investigation.
All patients will be entered into one week run-in period, when they will instructed to stop
any drug including any anti-cholinergics, if they are getting it before. Patient will be
supplied with a Bengali version micturition diary from and instructed to complete a 3 day
voiding diary. Average of three day will be calculated for 24 hours.
Overactive symptom score will be calculated by interviewing the patient for urinary symptom
for last 7 days.
The data sheet will be filled up after taking a brief interview of 15-20 minutes from the
patient.
Follow-up:
Patient in both group will be regularly followed up 12 weeks at 4 weeks interval.
Patient will be supplied with a Bengali version micturition diary from and instructed to
complete a 3 day voiding diary in each follow up schedule visit at the end of 4, 8 and 12
weeks of treatment to record the number of micturition, urgency, urge incontinence, nocturia,
the number of pad used, and voided volume of each micturition / 24 hours over 3 consecutive
days. Average of three day will be calculated for 24 hours.
Overactive symptom score will be calculated by interviewing the patient for urinary symptom
for last 7 days in each visit.
Patient will be evaluated for any adverse effects during the medication like dry mouth,
constipation, blurring vision, hypertension and headache that either intervention can cause
also be recorded in the predesigned data collection sheet. Severity of each of the adverse
effect will be assess as mild, moderate and severe.
Patient who will discontinue the drug will be excluded from data analysis. All patient will
contracted over telephone as schedule visit for follow up after initial treatment.
Technique of voiding diary:
Instruction for completing the 3-days voiding diary Please complete the voiding diary for a
total of 3 days. On the day that you start recording events in the voiding diary, print
Participant name and date at the top of the diary.
Start a new page for each day you keep the diary. Participant need to keep a diary for 3 full
consecutive days.
Measurement of functional improvement after intervention:
It will based on changes in the number of micturitions, urgency, and urge incontinence
episodes, nocturia episodes, the number of pad used, the voided volume of each micturition,
per 24 hours and OABSS after 4, 8 and 12 weeks of drug intervention. This record will compare
with baseline record.
Data Processing Plan:
Data collection instrument:
Data collection sheet Title:Efficacy and safety of mirabegron compared with solifenacin in
treatment of overactive bladder Name of the investigator: Dr. A. S. M. Kutub Uddin Awal Place
of study: Department of urology, BSMMU, Shahbag Dhaka.
Particulars of the patient:
Serial no……………………………. Date……………. Name………………………………………………………. Age……………… Sex:-Male/Female
Telephone no……………...................
Address:- Present ……………………………………………………………… ………………………………………………………………………
Group:
1. Mirabegron
2. Solifenacin Succinate
Presenting complaints:
1. Micturition frequency per 24 hours…………………………………….
2. Episodes of urgency per 24 hours………………………………………
3. Urge incontinence episodes per 24 hours……………………………..
4. Nocturia…………………………………………………………………….
5. Voided volume of each micturition (ml)…………………………………
6. Overactive bladder symptom score (OABSS) …………………………
Associated co-morbidity:
1. Diabetes mellitus
2. Hypertension
3. Stroke
Physical examination:
1. Pulse ………b/min,
2. BP…(mm Hg)
1. <139 and/or <90 2. 140-159 and/or 90-99 3. 160-179 and/or 100-109 4. ≥180 and/or ≥110
Investigations:
Hemoglobin ……………………gm/dl Random Blood Sugar ………….. mmol/l. Serum Creatinine …………mg/dl Urine
R/M/E Pus cells: 1= 0-4/HPF 2=≥ 5 HPF RBC: 1= 0-3/HPF 2=>3/HPF Urine Culture: 1= Positive
2=Negative USG of KUB&P with MCC and PVR: MCC= PVR= Follow up: (from voiding dairy) 4 Weeks 8
Weeks 12 Weeks
1. Micturition frequency per 24 hours
2. Episodes of urgency per 24 hours
3. Urge incontinence episodes per 24 hours
4. Nocturia episodes per 24 hours
5. Voided volume of each micturition (ml)
6. Overactive bladder symptom score (OABSS)
Adverse events:
4 Weeks 8 Weeks 12 Weeks Dry mouth Constipation Blurred vision Headache Hypertension
Discontinuation of medication due to adverse events Signature of the investigator
Data Collection:
The demographic information, relevant history, examination findings and investigation reports
and outcome of treatment of all the study subjects will be recorded in the data collection
sheet.
Patient will be supplied with a Bengali version micturition dairy from and instructed to
complete a 3-days voiding dairy prior to medication and each scheduled visit at week 4, 8 and
12 to record the micturition frequency, the presence of urgency and urge incontinence,
nocturia episodes, the number of pads used and the voided volume of each micturition. Average
of three day will be calculated for 24 hours.
Overactive symptom score will be calculated by interviewing the patient for urinary symptom
for last 7 days prior to medication and each scheduled visit.
Any adverse effect during the medication like Dry mouth, Constipation, Blurred vision,
Headache and Hypertension that can cause either intervention will be recorded in predesigned
data collection sheet.
Patient who will discontinue the drug will be excluded from data analysis. All patient will
be contracted telephone as scheduled for follow up after initial treatment.
The data sheet will fill up after taking a brief interview, review of records and documents
from the patients.
Data processing and analysis:
Data editing cleaning and reduction will be done by taking care for omission and illegal
entry of data. After compilation the data will present in the form of tables and figures as
necessary. After data collection all quantitative data will be expressed as mean ± standard
deviation and all categorical data will be presented as frequency. Variable will be compared
between the groups by Chi- squared test for qualitative variable (frequency, nocturia,
urgency) and two sample Z- test for quantitative variable (Overactive symptom score). The
statistical software SPSS Statistics version 19 (SPSS ,Chicago Illinois) will be used for
statistical analysis of data. Results will be considered significant if p-value <0.05.
Ethical implication:
Ethical clearance for the study will be taken from the Institutional Review Board (I.R.B) of
BSMMU prior to the commencement of this study.After the research protocol is approved by the
committee, permission for the study will be taken from the Department of Urology, BSMMU. The
aims and objectives of the study along with its procedure, risks and benefits of this study
will be explained to the study subjects in an easily understandable local language. A written
informed consent will be taken from all the study subjects without exploiting any of their
weakness. All the study subjects will be assured of adequate treatment of any complications
developed in relation to the purpose of the study. All the study subjects will be assured
about their confidentiality and freedom to withdraw themselves from the study at any time.
Quality assurance strategy:
During the study period quality assurance strategy will be maintained in every step by
meticulous conduct of study and avoidance of any bias. Patient will be select based upon
inclusion and exclusion criteria. Before drugs intervention proper counseling will be done
with patients regarding the procedure, possible complication and their management. Data
collected using questionnaire.
Operational definition:
Overactive bladder syndrome (OAB): Overactive bladder syndrome (OAB) is defined by the
International Continence Society as urinary urgency, with or without urgency incontinence,
usually with increased daytime frequency and nocturia in the absence of proven infection or
any other pathology.
Detrusor over activity (DO): It is an urodynamic observation characterized by involuntary
detrusor contraction during the filling phase which may be spontaneous or provoked and is the
cause of overactive bladder.
Frequency of micturition: The term is used to describe the need to urinate more often than
usual. In this study frequency of micturition will considered 8 or more voids per 24 hours.
Urgency: It is the complaint of a sudden compelling desire to pass urine which is difficult
to defer.
Urge incontinence: It is the complaint of involuntary leakage of urine, usually preceded by
urgency.
Nocturia: It is the complaint that the individual had to wake at night one or more times to
void.
Voided volume of each micturition: It is the volume of urine expelled via urethra in each
micturition.
Pad usage: The number of pads are use over 24-hours duration in patient with OAB.
Voiding dairy: It is use for assessing the number of micturitions, present of urgency and
urge incontinence, nocturia episodes, pads usage, and voided volume of each micturition.
Here, instructed of the patient to complete the 3-days voiding dairy prior to medication and
each scheduled visit. (Appendix-) Overactive Bladder Symptom Score (OABSS): This is a single
symptom score that employs a self-report questionnaire to quantify OAB symptom. The selected
symptom are- day time frequency, nighttime frequency, urgency and urgency incontinence for
the questionnaire. Overall score is the simple sum of the four symptom score. (Appendix-)
Informed Consent Form Title:efficacy and safety of mirabegron compared with solifenacin in
treatment of overactive bladder
Introduction:
I, Dr. A. S. M. Kutub Uddin Awal, work as student Master of Surgery(MS) (Urology) in the
Urology department of Bangabandhu Sheikh Mujib Medical University, Dhaka. Investigators are
researching on the treatment of overactive bladder disease that usually impinges on citizens
of adult age group. Participants are evocated to provide necessary information about it and
participate in our research.
The intention of this 'informed consent form' is to provide participant necessary information
that will help you take decision on whether you will participate in this research or not.
Participant will not have to take the decision right now. Participant can discuss with anyone
before you take the decision.
Aim and methods:
The aim of this 'informed consent form' is to return normal condition of overactive bladder
by alone oral medication without any operation.
This research will be conducted by the department of urology, Bangabandhu Sheikh Mujib
Medical University. For this research, 82 patients with overactive bladder will be included
for the study who will attend in the out patient department of Urology, Bangabandhu Sheikh
Mujib Medical University Hospital, Dhaka. There are two types of medication in this study to
treat overactive bladder. One of them, you will be taken one tablet in oral once daily. You
will have to come back to your physician in every 4 weeks for 3 times, to know the result of
research. You will be instructed to complete consecutive 3-days your voiding dairy prior to
each follow up scheduled visit. You will be first visited to the investigator at 4 weeks,
second time at 8 weeks and last scheduled visit at 12 weeks of treatment period.
If you participate in this study, then we will enroll you in our study and you will be
informed everything in details by your physician.
Risk in the research:
In this research participant may have to face a bit risk which is similar to that in case of
other medication. The most common harms of the study are dry mouth, constipation, blurred
vision, headache, and hypertension. But this risk are very little in favor of your proper
treatment. This harm develop in a few patients and usually control without treatment. There
is, however, provision for proper treatment of all kinds with appropriate physicians and all
necessary facilities within the hospital.
The benefit of participant in the research:
Participant will personally be benefited by your participation in this research. For example,
you will receive a more successful treatment option and quickly get free from your symptoms
and improvement of quality of life. At the same time, participant will be provided as pioneer
to take new treatment option.
Alternative:
The normal treatment of participant will proceed as per the general treatment procedure of
the hospital, even if participant do not participate in the research.
Expenditure:
To participant in this research, neither participant will have to carry an additional
expenditure nor you will be paid any amount of money.
Confidentiality:
All the information of the research will be kept confidential during the research and
afterwards. For the ease of the research you will be given one identification (ID) number.
All kind of documents with you ID number will be locked in file cabinet of the office. The
personal issue will not be second handed for data analysis, reporting and publishing and will
not be disclosed to anyone apart from the examiner of the research. So no one else can be
acquainted with any of your information.
Voluntary participation:
The participation of participant in this research is totally voluntary. Participant can deny
participating in the research or during the research you can withdraw yourself from the
research anytime you want. Your treatment will not be differentiated for that. None of legal
right will be breached if you sign this document.
Questionnaire:
Please let us know if participant have any question. We will try to answer your question at
our level best. If participant feel like throwing any question in future, then you may
contact with researcher Dr. A.S.M. Kutub Uddin awal, department of Urology, Room no 430,
Block no-C, Bangabandhu sheikh Mujib Medical University Hospital, Shahbag, Dhaka.
Consent of affirmation:
I am expressing my satisfaction after discussion and with the doctor (the doctor who will do
physical examination and the treatment of me) regarding this research. I have understood that
my participation in the research is voluntary and I can restrain myself from this research
anytime I want without being liable for anything. I have read the above mentioned information
/ the above mentioned information have read in front of me and I willingly express my
affirmation to participate in this research.
Name of the participant:
The Signature of the participant:
Date:
In case of the illiterate participant:
I am testifying that this consent form has read in front of the participant correctly and the
participant has the opportunity to ask question. I am confirming that the participant is
completely free and consciously agreed to participant in the research.
Name of the witness: The thumb print of the participant:
Signature of the witness:
Date:
