Efficacy of α-blocker or 5-ARI Withdrawal to Continued Combination Therapy on the Maintenance of LUTS in Men With BPH

Study Overview
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Brief Summary
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The investigators compare the efficacy of alpha-blocker and 5-ARI withdrawal to continued combination therapy on the maintenance of LUTS and improvement of quality of life outcomes in men with benign prostatic hyperplasia.

Detailed Description
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Benign Prostatic Hyperplasia (BPH) is the primary cause of lower urinary tract symptoms (LUTS). Combination therapy with an alpha-blocker and 5α reductase inhibitors (5-ARI) is the first-line treatment of BPH-related LUTS for the reduction of the size of the prostate and LUTS improvement. Combination therapy is tolerated well by most men; however, the incidence of adverse events is higher than with either therapy alone. In patients with improved LUTS following combination therapy, the aim of this study is based on the hypothesis that the withdrawal of either therapy will not increase the risk of LUTS aggravation while improving the quality of life. The investigators plan a prospective, randomized, open-label, parallel trial, comparing alpha-blocker withdrawal and 5-ARI withdrawal to continued combination therapy. Treatments will be allocated in a 1:1:1 ratio, based on IPSS score (≤30% decrease from baseline) and prostate volume (≤35% decrease from baseline).

Official Title
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A Prospective, Randomized, Open Label, Parallel Trial Comparing the Efficacy of α-blocker or 5-ARI Withdrawal to Continued Combination Therapy on the Maintenance of LUTS in Men With Benign Prostatic Hyperplasia

Conditions
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Prostatic Hyperplasia, Prostate Hyperplasia, Prostatic Hypertrophy

Intervention / Treatment
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* Drug: alpha-blocker or 5-ARI withdrawal
* Drug: Maintenance of alpha-blocker and 5-ARI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged ≥50 or <80 years AND On combination therapy (alpha-blocker and 5-ARI) ≥12 months AND IPSS score (≤30% decrease from baseline) AND Prostate volume (≤35% decrease from baseline) Exclusion Criteria: Suspected prostate cancer (PSA density >0.15 ng/ml/cc) requiring specific management On-going prostatitis or urinary retention Acontractile detrusor Neurogenic lower urinary tract dysfunction Urethral stenosis Patient unable or unwilling to provide written informed consent

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alpha-blocker withdrawal<br>receives 5-ARI monotherapy | Drug: alpha-blocker or 5-ARI withdrawal<br>* Withdrawal of either alpha-blocker or 5-ARI<br>* Other names: 5-ARI withdrawal;|
| Experimental: 5-ARI withdrawal<br>receives alpha-blocker monotherapy | Drug: alpha-blocker or 5-ARI withdrawal<br>* Withdrawal of either alpha-blocker or 5-ARI<br>* Other names: 5-ARI withdrawal;|
| Active Comparator: combination therapy<br>receives alpha-blocker and 5-ARI | Drug: Maintenance of alpha-blocker and 5-ARI<br>* Maintenance of alpha-blocker and 5-ARI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in International Prostate Symptom Score (IPSS) score from baseline | IPSS is the sum of the seven questions with each score ranging from 0 (best) to 5 (worst). IPSS is self-administered at screening and each time-point of month 3, 6, 12, and 18. Seven questions included are incomplete emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. The total IPSS score can range from 0-35 with severity catagories of mild (0 to 7), moderate (8 to 19) or severe (20 to 35). Month 18 is the primary timepoint and earlier timepoints are considered secondary. Change from baseline defined as difference between post-baseline value and baseline value. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Adverse events includes; dizziness, headache, pounding heartbeat, weakness. decreased sexual desire, impotence, ejaculatory disorder, gynecomastia, depression, and anxiety. | 3, 6, 12, 18 months | 
| Change in International Prostate Symptom Score (IPSS) from baseline | IPSS is the sum of the seven questions with each score ranging from 0 (best) to 5 (worst). IPSS is self-administered at screening and each time-point of month 3, 6, and 12. Seven questions included are incomplete emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. The total IPSS score can range from 0-35 with severity catagories of mild (0 to 7), moderate (8 to 19) or severe (20 to 35). Change from baseline defined as difference between post-baseline value and baseline value. | 3, 6, 12 months | 
| Change in Overactive bladder symptom score (OABSS) from baseline | The OABSS is a symptom assessment questionnaire designed to quantify OAB symptoms into a single score. The questionnaire consists of 4 questions on OAB symptoms with maximum scores ranging from 2 to 5: daytime frequency (2 points), night-time frequency (3 points), urgency (5 points), and UUI (5 points). OABSS is self-administered at screening and each time-point of month 3, 6, 12 and 18. Change from baseline defined as difference between post-baseline value and baseline value. | 3, 6, 12, 18 months | 
| Change in EuroQol five dimension scale (EQ-5D) score from baseline | The EuroQol five dimension descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ-5D is self-administered at screening and each time-point of month 3, 6, 12 and 18. Change from baseline defined as difference between post-baseline value and baseline value. | 3, 6, 12, 18 months | 
| Change in Qmax from baseline | The measurement of maximum urinary flow rate (Qmax) is widely used in the assessment of men complaining of lower urinary tract symptoms. Qmax is performed at screening and each time-point of month 3, 12, and 18. Change from baseline defined as difference between post-baseline value and baseline value. | 3, 12, 18 months | 
| Change in prostate volume from baseline | The measurement of prostate volume is performed at screening and at month 18. Change from baseline defined as difference between post-baseline value and baseline value. | 18 months | 
| Change in prostate-specific antigen (PSA) level from baseline | The measurement of prostate-specific antigen (PSA) level is performed at screening and at month 18. Change from baseline defined as difference between post-baseline value and baseline value. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alpha-blocker, 5α reductase inhibitor, withdrawal, benign prostatic hyperplasia, combination therapy