| CTRI Number |
CTRI/2019/02/017808 [Registered on: 25/02/2019] Trial Registered Prospectively |
| Last Modified On: |
30/01/2020 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
Comparison of Mirabegron, Tamsulosin and Solifenacin for relieving stent related symptoms. |
|
Scientific Title of Study
|
COMPARISON OF MIRABEGRON, SOLIFENACIN AND TAMSULOSIN IN RELIEVING URETERAL STENT RELATED SYMPTOMS:
A DOUBLE BLINDED RANDOMIZED CONTROL TRIAL
|
| Trial Acronym |
MIRASOTA |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Abhishek Chandna |
| Designation |
Senior Resident |
| Affiliation |
PGIMER Chandigarh |
| Address |
Advanced Urology Cente, ward no 26, Nehru hospital, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9592048405 |
| Fax |
|
| Email |
abhishek.chandna@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Santosh Kumar |
| Designation |
Additional Professor |
| Affiliation |
PGIMER |
| Address |
Advanced Urology Cente, ward no 26, Nehru hospital, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9417374067 |
| Fax |
|
| Email |
santoshsp1967jaimatadi@yahoo.co.in |
|
Details of Contact Person
Public Query
|
| Name |
Santosh Kumar |
| Designation |
Additional Professor |
| Affiliation |
PGIMER |
| Address |
Advanced Urology Cente, ward no 26, Nehru hospital, PGIMER, Chandigarh
CHANDIGARH
160012
India |
| Phone |
9417374067 |
| Fax |
|
| Email |
santoshsp1967jaimatadi@yahoo.co.in |
|
|
Source of Monetary or Material Support
|
| Dr Reddys pharmaceuticals |
|
|
Primary Sponsor
|
| Name |
Post Graduate Institute of Medical Education and Research |
| Address |
Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012
|
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Santosh Kumar |
Post Graduate Institute of Medical Education and Research |
Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 121002
Chandigarh
CHANDIGARH |
9417374067
santoshsp1967jaimatadi@yahoo.co.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Internal Ethics committee, Post Graduate Institute of Medical Education and Research |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: Q62||Congenital obstructive defects ofrenal pelvis and congenital malformations of ureter, (2) ICD-10 Condition: N20-N23||Urolithiasis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Mirabegron |
Patients with stents in situ and allocated into mirabegron arm shall be administered 50 mg oral mirabegron once a day orally
Duration 4 weeks for all endourological procedures (URSL, PCNL, ESWL,RIRS).
Upto 6 weeks in case of laparoscopic/robotic pyeloplasty based on surgeons discretion.
Medication to be continued upto removal of stent. |
| Comparator Agent |
Solifenacin |
Patients with stents in situ and allocated into solifenacin arm shall be administered 5 mg solifenacin once a day orally.
Duration 4 weeks for all endourological procedures (URSL, PCNL, ESWL,RIRS). Upto 6 weeks in case of laparoscopic/robotic pyeloplasty based on surgeons discretion. Medication to be continued upto removal of stent. |
| Comparator Agent |
Tamsulosin |
Patients with stents in situ and allocated into tamsulosin arm shall be administered 0.4 tamsulosin once a day orally.
Duration 4 weeks for all endourological procedures (URSL, PCNL, ESWL,RIRS). Upto 6 weeks in case of laparoscopic/robotic pyeloplasty based on surgeons discretion. Medication to be continued upto removal of stent. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
All patients above 18 years of age undergoing ureteral stent placement following any of the following surgeries/ procedures shall be enrolled in the study
1. Ureteroscopic lithotripsy (URSL)
2. Retrograde Intra-renal surgery (RIRS)
3. Percutaneous nephrolithotomy (PCNL)
4. Robot-assisted/ laparoscopic pyeloplasty
5. Extracorporeal shock wave lithotripsy (ESWL)
|
|
| ExclusionCriteria |
| Details |
1. Concomitant use of alpha blockers, anticholinergics, calcium channel blockers, corticosteroids and analgesics
2. Patients with long term indwelling ureteral stent prior to surgery ( > 4 weeks)
3. Patients undergoing open ureteral surgery
4. Patients with Overactive Bladder, Benign prostatic hyperplasia (IPSS score 8), and Neurogenic bladder
5. Patients with pre-operative untreated Urinary tract infection (UTI)
6. Pregnant or breast feeding women
7. Placement of bilateral ureteral stents
8. Patients with moderate or severe cardiovascular/cerebrovascular disease, severe uncontrolled hypertension or hepatic dysfunction
9. Patients with incomplete clearance of calculi following surgery
10. Patients with prior history of pelvic surgery or irradiation
11. Patients with prior history of bladder or prostatic surgery
12. Patients with other acute medical conditions that might influence the USSQ pain index
13. Any intra-operative event or surgeon’s discretion necessitating retention of ureteral stent in situ for more than 6 weeks
14. Incomplete clearance of calculus after 2 cycles of ESWL
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
|
|
Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare the efficacy and safety of mirabegron in relieving urinary symptoms in patients with ureteral stents measured by urinary index score of ureteric stent symptom questionnaire (USSQ) as compared to tamsulosin and solifenacin in a non-inferiority trial. |
Completion of follow up of target sample size |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To assess the efficacy of mirabegron in relieving ureteral stent related symptoms in other domains of USSQ viz. Pain Index score, General health Index score, Work performance score, Sexual matters score, Global quality of Life with stent in situ and additional problems |
Completion of follow up of target sample size |
| To compare the efficacy of tamsulosin and solfenacin in relieving ureteral stent related symptoms measured by various domains of USSQ. |
Completion of follow up of target sample size |
| To compare the adverse reaction profile of the tamsulosin, mirabegron and solifenacin in patients with ureteral stents |
Completion of follow up of target sample size |
|
|
Target Sample Size
|
Total Sample Size="120"
Sample Size from India="120"
Final Enrollment numbers achieved (Total)= "150"
Final Enrollment numbers achieved (India)="150" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
01/03/2019 |
| Date of Study Completion (India) |
28/01/2020 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Ureteral stents are used routinely in urological practice for therapeutic as well as palliative purposes. However, ureteral stents are associated with significant patient discomfort, with up to 80% patients reporting stent related symptoms following their insertion. Stent related symptoms comprise of numerous complaints including irritative voiding symptoms, incomplete emptying, flank and suprapubic pain as well as incontinence and hematuria. Various measures have been tried to prevent and alleviate stent related symptoms including mechanical as well as pharmacological therapy.
Pharmacological therapy including analgesics, antimuscarinics and alpha blockers remain the most effective alternative to manage stent related symptoms. Alpha blockers such as tamsulosin have shown benefical results in alleviating stent related symptoms as compared to alfuzosin in various studies. Multiple RCTs have demonstrated beneficial effect of antimuscarinics like solifenacin and tolterodine in improving stent related symptoms. However, alpha blocker commonly lead to orthostatic hypotension and dizziness, while antimuscarinics are associated with dry mouth, constipation and blurred vision. These add to patient discomfort and deter treatment compliance.
Mirabegron is a recently approved beta-3 adrenoceptor agonist for treatment of overactive bladder. It relaxes the detrusor muscle, especially during storage phase. Also, beta-3 adrenoceptors have been demonstrated in the mucosa as well as the muscular layers of the ureter. Beta-3 agonists should act on the distal ureter causing it’s dilatation, and alleviate stent related symptoms.In the bladder, they act on the involuntary contractions of the bladder and relieve overactive bladder like symptoms. Mirabegron has demonstrated better tolerability with lesser side effects as compared to antimuscarinics like tolterodine. Mirabegron has shown improvement in stent related symptoms, especially bodily pain and storage urinary symptoms in comparison to placebo in an open label study (Tae et al, 2018). 3 clinical trials (NCT02744430, NCT02095665, NCT02462837) are underway to evaluate its role in relieving stent related symptoms.
With this background, we propose to study the efficacy of this novel drug, mirabegron in comparison to established benchmarks, tamsulosin and solifenacin in reducing stent related symptoms in patients with ureteral stents.
|