Efficacy of Tadalafil/Solifenacin VS Tamsulosin/Solifenacin Combination Therapy for BPH/OAB

Study Overview
=================
Brief Summary
-----------------
The investigators will compare the efficacy and safety of tadalafil/solifenacin combination therapy versus tamsulosin/solifenacin combination therapy for the treatment of BPH/OAB in a randomized controlled trial (RCT).

Detailed Description
-----------------
Benign prostatic hyperplasia (BPH) is one of the most commonly diagnosed diseases in aging men worldwide. It is commonly associated with bothersome lower urinary tract symptoms (LUTS) including voiding symptoms such as decreased force of stream, intermittent stream, hesitancy and sensation of incomplete bladder emptying and storage symptoms such as frequent urination, urgency and nocturia. LUTS especially storage symptoms interfere with the daily activities and adversely affect the quality of life (QoL). Alpha-1 adrenergic receptor blockers have been used as a first-line treatment of LUTS suggestive of BPH (LUTS/BPH). Phosphodiesterase 5 inhibitors (tadalafil) have recently been used as initial treatment of LUTS/BPH. It was confirmed that once daily use of tadalafil 5 mg as a monotherapy is safe and has similar efficacy when compared to tamsulosin. Combination therapy could be used in patients who have BPH with overactive bladder (BPH/OAB) and still have persistent storage symptoms despite α1- adrenergic blockers. Anticholinergics in combination with α1- adrenergic blockers have been reported to be effective in those patients. Moreover, it has been reported that tadalafil has similar efficacy and safety to solifenacin when used in combination with tamsulosin for patients with persistent storage symptoms refractory to α1- adrenergic blockers. In another study, tadalafil/mirabegron combination therapy was used for BPH/OAB and its effect appeared to be greater than the effect of tadalafil monotherapy. Also, the combination therapy of tadalafil and solifenacin was approved to achieve higher response than tadalafil monotherapy in improvement of persistent storage symptoms associated with BPH. It was established that tadalafil can be used as a monotherapy to relieve both voiding and storage LUTS and it can be used in combination with tamsulosin or mirabegron to treat BPH/OAB. However, there is limited evidence regarding the efficacy and safety of the combined use of tadalafil and solifenacin for the treatment of BPH/OAB. Therefore, in this study, the investigators will compare the efficacy and safety of tadalafil/solifenacin combination therapy versus tamsulosin/solifenacin combination therapy for the treatment of BPH/OAB in a randomized controlled trial (RCT).

Official Title
-----------------
Efficacy of Tadalafil and Solifenacin Versus Tamsulosin and Solifenacin Combination Therapy for the Treatment of Benign Prostatic Hyperplasia With Overactive Bladder: A Randomized Controlled Trial

Conditions
-----------------
Benign Prostatic Hyperplasia, Overactive Bladder

Intervention / Treatment
-----------------
* Drug: Tadalafil 5mg
* Drug: Tamsulosin Hcl 0.4 mg
* Drug: solifenacin 10 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to give informed consent and reply to questionnaires. Age ≥ 45 years IPSS ≥ 8 OABSS ≥ 5, urgency subscore ≥2 Exclusion Criteria: Untreated urinary tract infection (UTI). Postvoid residual (PVR) more than 150 mL Neurogenic lower urinary tract dysfunction (LUTD). Depression or any psychogenic disorders. Diabetes mellitus, hypertension or severe cardiovascular disease. Prior radiation therapy to the pelvic area. Prostate cancer or bladder tumor. Past history of tuberculosis Allergy or contraindication to the used medications Urethral stricture Indwelling urethral catheter Vesical stone.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tadalafil / solifenacin combination therapy<br>Patients will be treated by combination of Tadalafil 5 mg + solifenacin 10 mg once daily for 12 weeks | Drug: Tadalafil 5mg<br>* patients with BPH/OAB will be treated with combination therapy of tadalafil plus solifenacin for 12 weeks in group 1<br>* Other names: rectalis 5 mg;Drug: solifenacin 10 mg<br>* patients with BPH/OAB will be treated with combination therapy of tadalafil plus solifenacin in group 1 and tamsulosin plus solifenacin in group 2 for 12 weeks<br>|
| Active Comparator: Tamsulosin / solifenacin combination therapy<br>Patients will be treated by combination of Tamsulosin 0.4 mg + solifenacin 10 mg once daily for 12 weeks | Drug: Tamsulosin Hcl 0.4 mg<br>* patients with BPH/OAB will be treated with combination therapy of tamsulosin plus solifenacin for 12 weeks in group 2<br>* Other names: tamsulosin 0.4 mg;Drug: solifenacin 10 mg<br>* patients with BPH/OAB will be treated with combination therapy of tadalafil plus solifenacin in group 1 and tamsulosin plus solifenacin in group 2 for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in international prostate symptom score (IPSS) from baseline | Change in IPSS from baseline will be compared. The change of -3 will be estimated as the minimal threshold for a meaningful change. The score has a range from 0 to 35 and higher scores means a worse outcome. | 3 months | 
| Change in overactive bladder symptom score (OABSS) from baseline | Change in OABSS from baseline will be compared. The change of -3 will be estimated as the minimal threshold for a meaningful change. The score has a range from 0 to 15 and higher scores means a worse outcome. | 3 months | 
| Change in IPSS-quality of life (QoL) score from baseline | Change in IPSS-QoL score from baseline will be compared. It is a single question with a score ranges from 0 to 6 and higher scores means a worse outcome. | 3 months | 
| Change in ultrasound measurement of post-void residual urine (PVR) from baseline | Change in PVR from baseline will be compared. | 3 months | 
| Change in maximum flow rate (Qmax) from baseline | Change in Qmax from baseline will be compared. | 3 months | 
| Adverse effects | Appearance of adverse effects related to the used medications will be reported. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in international index of erectile function-15 (IIEF-15) | change in IIEF-15 in sexually active patients will be compared. | 3 months | 
| change in ejaculatory domain of male sexual health questionnaire (Ej-MSHQ) | change in Ej-MSHQ in sexually active patients will be compared. | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Benign Prostatic Hyperplasia, Overactive Bladder, tadalafil, combination therapy for BPH