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

Sponsor

Gangnam Severance Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05023824

Collaborator

(none)

300

Enrollment

Location

Arms

35.9

Anticipated Duration (Months)

8.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia Prostate Hyperplasia Prostatic Hypertrophy	Drug: alpha-blocker or 5-ARI withdrawal Drug: Maintenance of alpha-blocker and 5-ARI	Phase 3

Detailed Description

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 8, 2020

Anticipated Primary Completion Date :

Dec 7, 2023

Anticipated Study Completion Date :

Dec 7, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: alpha-blocker withdrawal receives 5-ARI monotherapy	Drug: alpha-blocker or 5-ARI withdrawal Withdrawal of either alpha-blocker or 5-ARI Other Names: alpha-blocker withdrawal 5-ARI withdrawal
Experimental: 5-ARI withdrawal receives alpha-blocker monotherapy	Drug: alpha-blocker or 5-ARI withdrawal Withdrawal of either alpha-blocker or 5-ARI Other Names: alpha-blocker withdrawal 5-ARI withdrawal
Active Comparator: combination therapy receives alpha-blocker and 5-ARI	Drug: Maintenance of alpha-blocker and 5-ARI Maintenance of alpha-blocker and 5-ARI

Arm

Intervention/Treatment

Experimental: alpha-blocker withdrawal

receives 5-ARI monotherapy

Drug: alpha-blocker or 5-ARI withdrawal

Withdrawal of either alpha-blocker or 5-ARI

Other Names:

alpha-blocker withdrawal

5-ARI withdrawal

Experimental: 5-ARI withdrawal

receives alpha-blocker monotherapy

Drug: alpha-blocker or 5-ARI withdrawal

Withdrawal of either alpha-blocker or 5-ARI

Other Names:

alpha-blocker withdrawal

5-ARI withdrawal

Active Comparator: combination therapy

receives alpha-blocker and 5-ARI

Drug: Maintenance of alpha-blocker and 5-ARI

Maintenance of alpha-blocker and 5-ARI

Outcome Measures

Primary Outcome Measures

Change in International Prostate Symptom Score (IPSS) score from baseline [18 months]
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.

Secondary Outcome Measures

Number of adverse events [3, 6, 12, 18 months]
Adverse events includes; dizziness, headache, pounding heartbeat, weakness. decreased sexual desire, impotence, ejaculatory disorder, gynecomastia, depression, and anxiety.
Change in International Prostate Symptom Score (IPSS) from baseline [3, 6, 12 months]
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.
Change in Overactive bladder symptom score (OABSS) from baseline [3, 6, 12, 18 months]
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.
Change in EuroQol five dimension scale (EQ-5D) score from baseline [3, 6, 12, 18 months]
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.
Change in Qmax from baseline [3, 12, 18 months]
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.
Change in prostate volume from baseline [18 months]
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.
Change in prostate-specific antigen (PSA) level from baseline [18 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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