COMPARISON OF MIRABEGRON, SOLIFENACIN AND TAMSULOSIN IN RELIEVING URETERAL STENT RELATED SYMPTOMS:A DOUBLE BLINDED RANDOMIZED CONTROL TRIAL
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Post Graduate Institute of Medical Education and Research
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- 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.
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Computer generated randomization
- Masking
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Eligibility Criteria
- Ages
- 18.00 Year(s) to 70.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •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).
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
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.
Time Frame: Completion of follow up of target sample size
Secondary Outcomes
- 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)
- 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)