Advanced Benefits of Alpha-blocker Monotherapy on Lower Urinary Tracts Symptoms(LUTS) Patients (ABSOLUTE)

A Multicenter, Randomized, Double-blind, Clinical Study to Investigate the Efficacy and Safety of Treatment With Tamsulosin 0.2mg Mono and Tamsulosin 0.2mg, Finasteride 5mg Combination Therapy in Patients With LUTS/BPH

The purpose of this study is to evaluate the clinical efficacy of alpha-blocker monotherapy and alpha-blocker + 5-alpha reductase inhibitor combination therapy in benign prostate hyperplasia patients, and suggest guidelines of the combination therapy.

Study Overview

• Status: Unknown
• Conditions: Benign Prostate Hyperplasia
• Intervention / Treatment: Drug: Tamsulosin; Drug: Placebo; Drug: Finasteride

Detailed Description

Even though it should be decided on patients cautiously under careful consideration about prostate volume, Prostate Specific Antigen(PSA) level, symptom score and maximum uroflow, recently the combination therapy of alpha-blocker and 5-alpha reductase inhibitor has been tried imprudently in Korea.

As a result of several clinical trials which had conducted overseas for releasing the combination drug of alpha-blocker and 5-alpha reductase inhibitor, the superiority of the combination therapy has been proved, however, plenty of patients still don't derive additional profit from it.

Therefore, in this study, the investigators anticipate to meet with meaningful results on the clinical efficacy of alpha-blocker monotherapy and alpha-blocker + 5-alpha reductase inhibitor combination therapy in Korean benign prostate hyperplasia patients, and provide guidelines of the combination therapy.

• Study Type: Interventional
• Enrollment (Actual): 545
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Eulji General Hospital
  • Chungbuk
    • Cheongju, Chungbuk, Korea, Republic of
      • Chungbuk National University Hospital
  • Chungnam
    • Cheonan, Chungnam, Korea, Republic of
      • Soon Chun Hyang University Hospital Cheonan
  • Gyeoggi
    • Anyang, Gyeoggi, Korea, Republic of
      • Hallym University Sacred Heart Hospital
  • Gyeonggi
    • Bucheon, Gyeonggi, Korea, Republic of
      • Bucheon St. Mary's Hospital
    • Bucheon, Gyeonggi, Korea, Republic of
      • Soon Chun Hyang University Hospital Bucheon
    • Seongnam, Gyeonggi, Korea, Republic of
      • Seoul National University Bundang Hospital
    • Suwon, Gyeonggi, Korea, Republic of
      • Ajou University Hospital
  • Jeonnam
    • Hwasun, Jeonnam, Korea, Republic of
      • Chonnam National University Hwasun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male patients aged over 50
• Clinically diagnosed benign prostate hyperplasia(BPH)
• 8 ≤ IPSS ≤ 30
• 4 ml/sec ≤ Q max ≤ 15 ml/sec
• minimum voided volume ≥ 125 ml
• Post voided residual volume ≤ 250
• Volunteer who singed on informed consent documents

Exclusion Criteria:

• Past history of surgical procedure experience related to BPH
• Past history of taking 5-alpha reductase inhibitor(5-ARI) within 6 months before screening, or for more than 12 months regardless of the point of time
• Past history of taking alpha blocker within 2 weeks before screening
• Past history of acute urinary retention within 3 months before screening
• Serum PSA ≥ 10 ng/ml (but, in the case of 4 ng/ml ≤ PSA < 10 ng/ml, the patients can be included only if prostate cancer is excluded by prostate biopsy)
• Anatomical abnormalities of lower urinary tracts(urethrostenosis, diverticulosis, bladder neck contracture)
• Clinical status that affects voiding other than BPH(neurogenic bladder, Chronic Prostatitis/Chronic Pelvic Pain Syndrome, urinary infection, etc.)

• Unstable and significant medical condition including below

  • Unstable angina pectoris, myocardial infarction, cerebrovascular disease within 6 months before screening
  • Past history of malignant tumor including skin basal cell carcinoma within 5 years before screening
  • Medically uncontrollable diabetes mellitus, peptic ulcer disease
  • Severe hepatic diseases
  • Past history of renal failure or renal disease (serum creatinine > 1.4mg/dl)
  • Condition expected serious adverse event due to the investigational drug
• Other conditions considered not eligible for the trial upon investigator's judgement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Tamsulosin + Placebo; Tamsulosin 0.2mg + Placebo 5 mg daily until clinical progression	Drug: Tamsulosin; 1 tablet(0.2mg) orally q.d.; Other Names: Flomax; Harnal D (brand name in Asia); Drug: Placebo; 1 tablet(0.2mg) orally q.d.
ACTIVE_COMPARATOR: Tamsulosin + Finasteride; Tamsulosin 0.2mg + Finasteride 5 mg daily until clinical progression	Drug: Tamsulosin; 1 tablet(0.2mg) orally q.d.; Other Names: Flomax; Harnal D (brand name in Asia); Drug: Finasteride; 1 tablet(5mg) orally q.d.; Other Names: Proscar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Progression	One of below; Deterioration of the symptoms; Acute urinary retention; Renal failure; Recurrent urinary tract infection; Urinary incontinence; Surgical procedure related to benign prostate hyperplasia	1 & 2 months after baseline, and then every 3 months up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Prostate Symptom Score(IPSS)		1 & 2 months after baseline, and then every 3 months up to 4 years
International Consultation on Incontinence Modular Questionnaire(ICIQ) male LUTS-short form		every 6 months up to 4 years
Uroflowmetry	including Qmax, voided volume and post-void residual volume(PVR)	every 6 months up to 4 years
Prostate volume		every 1 year up to 4 years
Global Response Assessment(GRA)		every 1 year up to 4 years
PSA level	PSA level will be examined in the central laboratory and be reported to each center as an adjusted number. It is because PSA level tends to decrease to 50% of baseline after taking finasteride for 1~4 years, so there is possibilities that the blindedness is broken with the actual result.	every 1 year up to 4 years
Blood Chemistry	including Sodium, Potassium, Glucose, Urea nitrogen, Creatinine, ASpartate Transaminase(AST), ALanine Transaminase(ALT), Total bilirubin	every 1 year up to 4 years
Adverse Events		every visit up to 4 years
Physical examination	Digital Rectal Exam, Breast exam	every 1 year up to 4 years
Male Sexual Health Questionnaire		every 6 months up to 4 years

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Astellas Pharma Korea, Inc.; Medical Research Collaborating Center, Seoul, Korea
• Investigators: Principal Investigator: Soo Woong Kim, M.D., Seoul National University Hospital

Publications and helpful links

General Publications

• Shapiro E, Lepor H. Pathophysiology of clinical benign prostatic hyperplasia. Urol Clin North Am. 1995 May;22(2):285-90.
• Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet. 1991 Aug 24;338(8765):469-71. doi: 10.1016/0140-6736(91)90543-x.
• Bosch JL, Kranse R, van Mastrigt R, Schroder FH. Reasons for the weak correlation between prostate volume and urethral resistance parameters in patients with prostatism. J Urol. 1995 Mar;153(3 Pt 1):689-93. doi: 10.1097/00005392-199503000-00039.
• Chung TG, Chung J, Lee MS, Ahn H. Prevalence of benign prostatic hyperplasia in Jeong-Eup Area: community-based study. Korean J Urol 1999;40:52-8.
• The prevalence of benign prostatic hyperplasia in elderly men in Korea: a community-based study. Park HK, Park H, Cho S, Bae J, Jeong S, Hong SK, et al. Korean J Urol 2009;50:843-7.
• Lepor H, Gup DI, Baumann M, Shapiro E. Laboratory assessment of terazosin and alpha-1 blockade in prostatic hyperplasia. Urology. 1988 Dec;32(6 Suppl):21-6.
• Noble AJ, Chess-Williams R, Couldwell C, Furukawa K, Uchyiuma T, Korstanje C, Chapple CR. The effects of tamsulosin, a high affinity antagonist at functional alpha 1A- and alpha 1D-adrenoceptor subtypes. Br J Pharmacol. 1997 Jan;120(2):231-8. doi: 10.1038/sj.bjp.0700907.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ANTICIPATED): February 1, 2017
• Study Completion (ANTICIPATED): June 1, 2017

Study Registration Dates

• First Submitted: November 18, 2012
• First Submitted That Met QC Criteria: November 27, 2012
• First Posted (ESTIMATE): November 29, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): May 14, 2014
• Last Update Submitted That Met QC Criteria: May 13, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Tamsulosin; Finasteride; 5 alpha reductase inhibitor; Proscar; Lower Urinary Tracts Symptoms; alpha blocker; Harnal D
• Additional Relevant MeSH Terms: Pathologic Processes; Urological Manifestations; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; 5-alpha Reductase Inhibitors; Tamsulosin; Finasteride
• Other Study ID Numbers: TMS1011