(Phosphodiesterase 5 Inhibitors & α-blockers): Single Versus Combined Therapy in Benign Prostatic Hyperplasia

Study Overview
=================
Brief Summary
-----------------
To compare between efficacy of phosphodiesterase5 inhibitors (tadalafil 5 mg) and Alpha Blockers (tamsulosin 0.4 mg) monotherapy vs combined therapy in treatment of lower urinary tract symptoms of benign prostatic hyperplasia.

Detailed Description
-----------------
The proposed research aims to answer the question about efficacy and safety of phosphodiesterase 5 inhibitors (tadalafil 5 mg) and Alpha Blockers (tamsulosin 0.4 mg) monotherapy vs combined therapy in treatment of lower urinary tract symptoms of benign prostatic hyperplasia . Benign prostatic hyperplasia (BPH) is a disorder histologically characterized as the non-malignant hyperplasia of prostatic cells. Most of patients with BPH present with lower urinary tract symptoms (LUTS). About half of men develop BPH, among those; about half develop some degree of bladder outlet obstruction (BOO). BOO and/or changes in smooth muscle tone and resistance that can accompany BPH may result in (LUTS). Alpha-blockers have been widely used for the treatment of LUTS/BPH for a long time. Some alpha-blockers may cause ejaculatory dysfunction in some individuals. Tadalafil, a (PDE-5), was approved by the Food and Drug Administration (FDA) for the treatment of (ED) in 2003 and for the treatment of BPH in 2011. The PDE5 inhibitors are used in the treatment of ED and there are increasing data of effects of these drugs on bladder and urethral relaxation as well as of prostatic smooth muscles that may relief the symptoms of BPH. Medical treatments for LUTS/BPH are able to significantly impact on sexual function. Sexual side effects like ejaculatory dysfunction, reduced or lost libido, and ED have been widely reported in patients treated with alpha blockers (ABs) and 5-alpha reductase inhibitors, the most utilized drugs for the treatment of LUTS/BPH. The inclusion of Tadalafil in complex of combined conservative therapy of patients with BPH not only improves sexual function but has a positive effect on symptoms of the disease and the psychological state of the patient.

Official Title
-----------------
Comparative Study Between Fixed Dose Monotherapy (Phosphodiesterase 5 Inhibitors or Alpha Blockers) Versus Combined Therapy in Benign Prostatic Hyperplasia Patients With Lower Urinary Tract Symptoms

Conditions
-----------------
Benign Prostatic Hyperplasia

Intervention / Treatment
-----------------
* Drug: Phosphodiesterase 5 Inhibitors
* Drug: Alpha Blockers
* Drug: Combined Alpha Blockers and Phosphodiesterase 5 Inhibitors


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1 - Men > 45 years with LUTS/BPH for > 6 months 2- IPSS of ≥ 8 and Qmax of ≥ 4 to≤ 15 mL/s Exclusion Criteria: PSA level of > 10.0 ng/mL (if ≥ 4.0 to≤ 10.0 ng/mL prostate cancer will be excluded). Post-voidresidual urine volume of ≥ 150 mL. Previous Urine Retention or Urethral Catheterization . other pathology such as urinary bladder stone , bladder mass or neurogenic bladder . Any case of LUTS other than BPH (urinary bladder stone, neurogenic bladder, bladder neck contracture,rethral stricture, bladder cancer, acute or chronic prostatitis, acute or chronic urinary tract infection). patients supposed to undergo intraocular operation (as cataract operation) . History of head injury or cerebrovascular stroke or spinal injury. pelvic fracture. Uncontrolled diabetic patient. Patients with chronic obstructive lung disease on medical treatment. Parasympatholytic drugs are contraindicated during the study. 12. Patients refusing to share in the study.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 75 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
Interventional Model Description: A total of (120) patients with LUTS due to BPH fulfilling the inclusion criteria will be included in this study. Patients will be randomly divided into 3 groups: Group A: Forty patients with LUTS due to BPH will be given tamsulosin 0.4 mg for 12 weeks. Group B: Forty patients with LUTS due to BPH will be given tadalafil 5 mg for 12 weeks. Group C: Forty patients with LUTS due to BPH will be given combined therapy for 12 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Forty patients with LUTS due to BPH will be given tamsulosin 0.4 mg for 12 weeks. | Drug: Alpha Blockers<br>* A total of (120) patients with LUTS due to BPH fulfilling the inclusion criteria will be included in this study. Patients will be randomly divided into three groups: Group A: Forty patients with LUTS due to BPH will be given tamsulosin 0.4 mg for 12 weeks. Group B: Forty patients with LUTS due to BPH will be given tadalafil 5 mg for 12 weeks. Group C: Forty patients with LUTS due to BPH will be given combined therapy for 12 weeks.<br>* Other names: Tamsulin 0.4 mg oral tablet;|
| Active Comparator: Group B<br>Forty patients with LUTS due to BPH will be given tadalafil 5 mg for 12 weeks. | Drug: Phosphodiesterase 5 Inhibitors<br>* A total of (120) patients with LUTS due to BPH fulfilling the inclusion criteria will be included in this study. Patients will be randomly divided into three groups: Group A: Forty patients with LUTS due to BPH will be given tamsulosin 0.4 mg for 12 weeks. Group B: Forty patients with LUTS due to BPH will be given tadalafil 5 mg for 12 weeks. Group C: Forty patients with LUTS due to BPH will be given combined therapy for 12 weeks.<br>* Other names: tadalafil 5 mg oral Tablet;|
| Active Comparator: Group C<br>Forty patients with LUTS due to BPH will be given combined therapy(tamsulosin 0.4 mg and tadalafil 5 mg) for 12 weeks. | Drug: Combined Alpha Blockers and Phosphodiesterase 5 Inhibitors<br>* A total of (120) patients with LUTS due to BPH fulfilling the inclusion criteria will be included in this study. Patients will be randomly divided into three groups: Group A: Forty patients with LUTS due to BPH will be given tamsulosin 0.4 mg for 12 weeks. Group B: Forty patients with LUTS due to BPH will be given tadalafil 5 mg for 12 weeks. Group C: Forty patients with LUTS due to BPH will be given combined therapy for 12 weeks.<br>* Other names: Tadalafil 5 mg oral Tablet and Tamsulin 0.4 mg oral tablet;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in International prostate symptom score (IPSS) after 12 weeks | The IPSS is made up of 7 questions related to voiding symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms and 20 to 35 indicates severe symptoms. | At start of study and after 12 weeks from drug intake | 
| Change in International index of erectile function (IIEF) after 12 weeks | The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for diagnostic evaluation of ED severity. | At start of study and after 12 weeks from drug intake | 
| Change in Maximal urinary flow rate (Qmax) after 12 weeks | The flow rate is calculated as milliliters (ml) of urine passed per second. Both average and top flow rates are measured. The fastest flow rate, also known as Qmax, is used to understand if a block or obstruction is severe. | At start of study and after 12 weeks from drug intake | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phosphodiesterase5 inhibitors and Alpha Blockers