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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Hyperplasia; Prostatic Hypertrophy; Prostate Hyperplasia
• Intervention / Treatment: Drug: alpha-blocker or 5-ARI withdrawal; Drug: Maintenance of alpha-blocker and 5-ARI

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 Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kyo Chul Koo, MD, PhD; Phone Number: 82-01099480342; Email: gckoo@yuhs.ac
• Study Contact Backup: Name: Kwang Suk Lee, MD, MMS; Phone Number: 82-01089246674; Email: calmenow@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-720
    • Recruiting
    • Gangnam Severance Hospital, Yonsei University College of Medicine
    • Contact: Kyo Chul Koo, MD, PhD; Phone Number: 82-01099480342; Email: gckoo@yuhs.ac
    • Contact: Kwang Suk Lee, MD, MMS; Phone Number: 82-01089246674; Email: calmenow@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gangnam Severance Hospital
• Investigators: Principal Investigator: Kyo Chul Koo, MD, PhD, Yonsei University

Publications and helpful links

General Publications

• Barkin J, Guimaraes 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):461-6. doi: 10.1016/s0302-2838(03)00367-1.
• 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. doi: 10.5489/cuaj.520.

Helpful Links

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• Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Anticipated): December 7, 2023
• Study Completion (Anticipated): December 7, 2023

Study Registration Dates

• First Submitted: August 15, 2021
• First Submitted That Met QC Criteria: August 21, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 21, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: combination therapy; benign prostatic hyperplasia; withdrawal; alpha-blocker; 5α reductase inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Pathological Conditions, Anatomical; Prostatic Hyperplasia; Hyperplasia; Hypertrophy; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic alpha-Antagonists
• Other Study ID Numbers: 3-2020-0451 (Other Grant/Funding Number: Handok Pharmaceutical)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes