Efficacy of Mirabegron Versus Tamsulosin Versus Solifenacin for Treatment of Ureteral Stents-Related Symptoms

Sponsor

Mansoura University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04325880

Collaborator

(none)

240

Enrollment

Location

Arms

Anticipated Duration (Months)

34.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this prospective, single-centre randomized controlled trial is to assess the efficacy of three different drugs in treatment of ureteral stents related symptoms (Beta 3 adrenergic receptor agonist; Mirabegron 50mg) vs. (Alpha 1 adrenergic receptor antagonist; Tamsulosin 0.4mg) vs. (Anticholinergic; Solifenacin 10 mg) using validated symptoms questionnaires.

In addition, adverse events of the utilized medications will be monitored during study period as a secondary objective.

Condition or Disease	Intervention/Treatment	Phase
Ureteral Stent Stent Related Symptoms	Drug: Mirabegron 50 MG Drug: Tamsulosin Drug: Solifenacin Succinate 10 MG Drug: Placebo oral tablet	Phase 3

Detailed Description

Indwelling ureteral stents are specialized catheters designed to alleviate obstruction by maintaining the patency of the ureteral lumen and to splint the ureter by acting as a scaffold to promote organized tissue healing. (1)

Common issues associated with contemporary ureteral stents include stent-related pain, hematuria, dysuria, urgency, infection, and encrustation (2). Majority of patients (80%) reported one or more urinary symptoms with over 80% of patients experience stent-related pain that affects daily activities, 58% report reduced work capacity, and 32%report sexual dysfunction (2). In addition, as many as 32% of patients had ureteral stents removed sooner than anticipated because of these complications (3).

Considering this high prevalence of ureteral stent related symptoms (uSRS) among patients and its potential impact on quality of life (QoL), adequate management of these bothering symptoms was the point of research over the last decades (4).

The exact mechanism involved in uSRS is not yet known; however, many authors report that such symptoms are associated with ureteral spasms, urinary reflux attributable to ureteral stent, or trigonal irritation (5).

Different novel types of stents have been developed and evaluated to reduce uSRS; however, there is still controversy regarding their clinical application (6). Conversely, pharmacological therapy, including anticholinergics and alpha-blockers, remains the most effective option to manage uSRS (7).

The role of a-blockers in reducing uSRS involves reduction of bladder outlet resistance to alleviate flank pain in male patients with preexisting bladder outlet obstruction (BOO). It has been proposed that relaxing the distal ureter and irritation of the trigone decreases bladder outlet resistance and voiding pressure, thereby potentially decreasing the incidence of renal reflux and subsequent flank pain (8) . Otherwise, anticholinergic agents may have an effect on involuntary contractions of the bladder induced by the distal end of ureteral stents with subsequent relief of uSRS (9).

The above-mentioned drugs, however, are not easy to apply to some patients with co-morbidities because of the potential side effects. The most common medication-related complications of a-blockers are dizziness and orthostatic hypotension. Depending on the type of medication, medication-related adverse events are reported at a rate of 5% to 20% (10). In addition, anticholinergic agents have various adverse effects that decrease treatment compliance, such as dry mouth, constipation, blurred vision and dyspepsia (11).

Beta-3 agonist mirabegron is believed to be responsible for the relaxation of the detrusor smooth muscle during the storage phase (12). It helps relax the detrusor smooth muscle, and results in increased bladder capacity without any changes in micturition pressure, post-void residual urine volume, or voiding contractions.

Considering the function of mirabegron as a therapeutic agent for overactive bladder (OAB), mirabegron is assumed to be effective for relieving voiding symptoms attributable to uSRS (13).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

Efficacy of Mirabegron Versus Tamsulosin Versus Solifenacin for Treatment of Ureteral Stents-Related Symptoms: a Randomized Controlled Trial

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo arm Patients in this arm will receive a placebo formula	Drug: Placebo oral tablet Patients in this arm will receive placebo oral tablet once daily
Active Comparator: Mirabegron arm Patients in this arm will receive Mirabegrone 50 mg once daily	Drug: Mirabegron 50 MG Patients in this arm will receive Mirabegrone 50 MG once daily
Active Comparator: Tamsulosin arm Patients in this arm will receive tamsulosin o.4 mg once daily	Drug: Tamsulosin Patients in this arm will receive Tamsulosin o.4 MG once daily
Active Comparator: Solifenacin arm Patients in this arm will receive solifenacin 10 mg once daily	Drug: Solifenacin Succinate 10 MG Patients in this arm will receive Solifenacin Succinate 10 MG once daily

Outcome Measures

Primary Outcome Measures

Improvement in stent related symptoms using ureteral stent symptoms questionnaire (USSQ) [4 weeks]
The effect of the assigned treatment on improvement of stent related symptoms will be assessed at the time of stent removal using ureteral stent symptoms questionnaire (USSQ)

Secondary Outcome Measures

Adverse event of medications [4 weeks]
Side effects of the assigned treatment will be monitored

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients (aged 19-80 years)
Undergo unilateral uncomplicated retrograde rigid ureteroscopy (URS) or retrograde intrarenal surgery (RIRS) with planned ureteral stent insertion.

Exclusion Criteria:

Patients with neurogenic bladder, OAB syndrome, and neurological and psychiatric diseases
Residual ureteral or renal stones after the procedure
Preoperative febrile UTI
pregnancy or breastfeeding
Bilateral ureteroscopic surgery
Single kidney
Chronic kidney disease
Cardiovascular or cerebrovascular disease
Hepatic dysfunction
History of pelvic surgery or irradiation
History of bladder or prostate surgery
Other acute medical conditions as acute gastroenteritis, osetoarthritis that might influence the patient QoL
Preoperative indwelling of ureteral stent for relief of stone-related pain or sepsis