Clinical trial NCT03632772: Comparison of Solifenacin and Mirabegron in Treatment of Overactive Bladder Symptoms in Men After TURP
Official title: Comparative Study of Solifenacin and Mirabegron in Treatment of Overactive Bladder Symptoms in Men After Transurethral Resection of the Prostate - A Randomized Prospective Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Overactive Bladder Syndrome
Keywords: Overactive bladder
Transurethral Resection of the Prostate
Pharmacotherapy
Mirabegron
Solifenacin
Lead sponsor: Buddhist Tzu Chi General Hospital
Sponsor class: OTHER
First posted: 2018-08-15
Enrollment: 130
Sex: MALE
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Urinary frequency urgency and urgency urinary incontinence (UUI) are commonly encountered in patients after transurethral prostatectomy (TURP) or transurethral incision of the prostate (TUIP). Antimuscarinics has been widely used to treat OAB and around 70% of patients can improve symptoms after treatment. Beta-3 adrenoceptor agonist (mirabegron) can also decrease DO and improve OAB symptoms. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg was more effective than mirabegron 50mg alone, but with more anticholinergic side effects. However, there has been no clinical trial to compare which drug provides more benefit to decrease the OAB symptom severity immediately after TURP. This study tries to compare the safety and therapeutic efficacy between solifenacin and mirabegron in men with BPH and having OAB symptoms immediately after TURP.

This study was designed as a prospective, randomized trial to compare the safety and efficacy of OAB medication on the decrease of overactive bladder symptoms score (OABSS) and urgency severity score (USS) between solifenacin 5mg QD and mirabegron 50mg QD in men with BPH undergoing TURP. A total of 130 male patients with BPH and undergo TURP or TUIP will be enrolled. The primary end point is the change of USS from baseline to 4 weeks after catheter removal and starting OAB medication. Secondary end-points include the changes of OABSS, frequency episodes, urgency episodes, UUI episodes in the 3-day voiding diary, maximum flow rate (Qmax), voided volume and PVR, International Prostate Symptom Score (IPSS) and quality of life index (QoL-I) from baseline to 2 weeks and 4 weeks.

We expect that patients receiving solifenacin and mirabegron might have similar therapeutic effects on decrease of USS, but patients who received mirabegron might have less adverse events such as dry mouth or difficulty in urination.

Detailed description: Introduction:

Urinary frequency urgency and urgency urinary incontinence (UUI) are commonly encountered in patients after transurethral prostatectomy (TURP) or transurethral incision of the prostate (TUIP). \[1\] Patients usually bother by these overactive bladder (OAB) symptoms. The causes of postprostatectomy OAB might be detrusor overactivity (DO) before TURP, increase afferent input due to acute inflammation after TURP, or a weak urethral sphincter which cannot hold urine at the bladder capacity. Antimuscarinics and beta-3 adrenoceptor agonist are two different classes of medication for OAB. \[2\] Antimuscarinics has been widely used to treat OAB and around 70% of patients can improve symptoms after treatment. Beta-3 adrenoceptor agonist (mirabegron) can also decrease DO and improve OAB symptoms. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg was more effective than mirabegron 50mg alone, but with more anticholinergic side effects. \[3\] However, antimuscarnics might decrease detrusor contractility and result in increase of postvoid residual (PVR) volume. Current clinical studies reveal that mirabegron does not impair detrusor contractility or increase PVR. \[4\] Under this consideration, mirabegron has been widely used to treat male lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH). \[5\] However, there has been no clinical trial to compare which drug provides more benefit to decrease the OAB symptom severity immediately after TURP. This study tries to compare the safety and therapeutic efficacy between solifenacin and mirabegron in men with BPH and having OAB symptoms immediately after TURP.

Material and methods:

Objectives and Endpoints: This study was designed as a prospective, randomized trial to compare the safety and efficacy of OAB medication on the decrease of overactive bladder symptoms score (OABSS) and urgency severity score (USS) between solifenacin 5mg QD and mirabegron 50mg QD in men with BPH undergoing TURP.

Randomization: Permuted block randomization method will be applied to generate randomization codes. Each randomization number will be assigned to individual patient according to the time-sequence for screened patient become eligible.

Expected Results:

Patients receiving solifenacin and mirabegron might have similar therapeutic effects on decrease of USS, but patients who received mirabegron might have less adverse events such as dry mouth or difficulty in urination.

Eligibility criteria: Inclusion Criteria:

1. Male patients with BPH and undergo TURP or TUIP.
2. Patients void smoothly after catheter removal.
3. No active urinary tract infection.
4. No gross hematuria or blood clot obstruction.
5. Patient or his care giver can complete voiding diary and report symptoms.

Exclusion Criteria:

1. Patients have overt neurological diseases such as cerebrovascular disease, senile dementia or spinal cord injury.
2. Patients have severe medical disease and completely immobile.
3. Patients have PVR larger than 150ml.
4. Patients do not have OAB after TURP.

Primary outcomes:
measure: Urgency Severity Scale (USS)
timeFrame: from baseline to 4 weeks
Secondary outcomes:
measure: Overactive Bladder Symptom Score (OABSS)
timeFrame: from baseline to 2 weeks and 4 weeks.
measure: frequency episodes, urgency episodes, urgency urinary incontinence (UUI) episodes in the 3-day voiding diary
timeFrame: from baseline to 2 weeks and 4 weeks.
measure: maximum flow rate (Qmax)
timeFrame: from baseline to 2 weeks and 4 weeks.
measure: voided volume (Vol)
timeFrame: from baseline to 2 weeks and 4 weeks.
measure: Postvoid residual volume (PVR)
timeFrame: from baseline to 2 weeks and 4 weeks.
measure: International Prostate Symptom Score (IPSS)
timeFrame: from baseline to 2 weeks and 4 weeks.
measure: quality of life index (QoL-I)
timeFrame: from baseline to 2 weeks and 4 weeks.
Other outcomes:
Locations:
city: Hualien city
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
Study officials:
affiliation: Department of Urology, Buddhist Tzu Chi General Hospital, Hualien
name: Hann-Chorng Kuo, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seki N, Yuki K, Takei M, Yamaguchi A, Naito S. Analysis of the prognostic factors for overactive bladder symptoms following surgical treatment in patients with benign prostatic obstruction. Neurourol Urodyn. 2009;28(3):197-201. doi: 10.1002/nau.20619.
citation: Yamada S, Ito Y, Nishijima S, Kadekawa K, Sugaya K. Basic and clinical aspects of antimuscarinic agents used to treat overactive bladder. Pharmacol Ther. 2018 Sep;189:130-148. doi: 10.1016/j.pharmthera.2018.04.010. Epub 2018 Apr 27.
citation: Kelleher C, Hakimi Z, Zur R, Siddiqui E, Maman K, Aballea S, Nazir J, Chapple C. Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis. Eur Urol. 2018 Sep;74(3):324-333. doi: 10.1016/j.eururo.2018.03.020. Epub 2018 Apr 23.
citation: Wada N, Iuchi H, Kita M, Hashizume K, Matsumoto S, Kakizaki H. Urodynamic Efficacy and Safety of Mirabegron Add-on Treatment with Tamsulosin for Japanese Male Patients with Overactive Bladder. Low Urin Tract Symptoms. 2016 Sep;8(3):171-6. doi: 10.1111/luts.12091. Epub 2015 Feb 17.
citation: Nitti VW, Rosenberg S, Mitcheson DH, He W, Fakhoury A, Martin NE. Urodynamics and safety of the beta(3)-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. J Urol. 2013 Oct;190(4):1320-7. doi: 10.1016/j.juro.2013.05.062. Epub 2013 May 30.