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

Prostatic Hyperplasia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05023824
• Other study ID #: 3-2020-0451
• Secondary ID: 3-2020-0451
• Status: Recruiting
• Phase: Phase 3
• Start date: December 8, 2020
• Est. completion date: December 7, 2023

Study information

• Verified date: August 2021
• Source: Gangnam Severance Hospital
• Contact: Kyo Chul Koo, MD, PhD
• Phone: 82-01099480342
• Email: gckoo[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 7, 2023
• Est. primary completion date: December 7, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperplasia
• Hypertrophy
• Prostate Hyperplasia
• Prostatic Hyperplasia
• Prostatic Hypertrophy

Intervention

Drug:
• alpha-blocker or 5-ARI withdrawal
Withdrawal of either alpha-blocker or 5-ARI
• Maintenance of alpha-blocker and 5-ARI
Maintenance of alpha-blocker and 5-ARI

Locations

Country	Name	City	State
Korea, Republic of	Gangnam Severance Hospital, Yonsei University College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Gangnam Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Barkin J, Guimarães M, Jacobi G, Pushkar D, Taylor S, van Vierssen Trip OB. Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol. 2003 Oct;44(4): — View Citation

Nickel JC, Barkin J, Koch C, Dupont C, Elhilali M. Finasteride monotherapy maintains stable lower urinary tract symptoms in men with benign prostatic hyperplasia following cessation of alpha blockers. Can Urol Assoc J. 2008 Feb;2(1):16-21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride
•   Finasteride monotherapy maintains stable lower urinary tract symptoms in men with benign prostatic hyperplasia following cessation of alpha blockers