The Clinical Efficacy of Non-steroidal Anti-inflammation Drugs in Patients With Benign Prostatic Hyperplasia

The Clinical Efficacy of Non-steroidal Anti-inflammation Drugs in Patients With Benign Prostatic Hyperplasia: A Prospective Randomized Multicenter Trial

Non-steroidal Anti-inflammation Drugs can effectively reduce the lower urinary tract symptoms from benign prostatic hyperplasia

Study Overview

• Status: Withdrawn
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Drug: selective alpha 1-blockers; Drug: celecoxib; Drug: alpha-blocker and NSAID

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital

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:

• Who had the treatment of BPH with alpha-1 blockers for more than 3 months
• Who have the IPSS(International Prostatic Symptom Score) >= 15
• Who have the maximum flow rate(Qmax) < 15 with voided volume > 150mL
• Who have the PPBC(patient's perception of bladder condition) >= 3 (The PPBC was assessed by the use of a six point ordered categorical scale(1-6 point). The higher score means the higher bother)
• Who had the PSA level < 4 ng/mL within 6 months (But, the patient who are revealed not to have prostate cancer by prostate biopsy can be included even if he had PSA level of 4-10 ng/mL)
• Who underwent the transrectal ultrasound of prostate within 6 months
• Who can understand this study and can give the informed consent

Exclusion Criteria:

• Who had regular intake of 5-alpha reductase inhibitor or NSAID within 6 months before screening
• Who have peptic ulcer and/or asthma
• Who have urologic malignancies such as prostate cancer and bladder cancer
• Who have urethral strictures, large bladder diverticuli, and bladder neck contractures
• Who had surgical treatment for BPH
• Who have histories of bladder and/or urethra
• Who have serum PSA level more than 10 ng/ml
• Who have histories of orthostatic hypotension
• Who have serum creatinine level more than 2.0 mg/dl
• Who have serum ALT and/or AST level more than 1.5 times of normal upper limit
• Who have heart failure
• Who have histories of bacterial prostatitis within 1 year
• Who have histories of active urinary tract infection within 1 month
• Who have histories of the biopsy of bladder and prostate within 1 month
• Who are unable to void
• Who use pads because of incontinences
• Who have hypersensitivities for alpha blockers that include quinazoline, NSAID, aspirin, sulfonamide
• Who have histories of unstable angina, myocardial infarction, and cerebrovascular accident within 6 months
• Who have neurogenic bladder due to multiple sclerosis, Parkinson's disease, Spinal injuries and etc.
• Who have thinking disturbances
• Who have histories of abuses of alcohol and/or other drugs
• Who seem to be not fit to this study by the decision of investigators

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
Active Comparator: Alpha-blocker; Alpha-blocker only	Drug: selective alpha 1-blockers; Continued medication that the patient had before the enrollment of this study (tamsulosin 0.2mg, alfuzosin 10mg, doxazosin 4, 8mg, or terazosin 2-10mg daily for 8 weeks); Other Names: doxazosin; terazosin; tamsulosin; alfuzosin
Active Comparator: NSAID; NSAID only	Drug: celecoxib; 200mg daily for 8 weeks
Experimental: alpha-blocker and NSAID; Combination treatment of alpha-blocker and NSAID	Drug: alpha-blocker and NSAID; amsulosin 0.2mg, alfuzosin 10mg, doxazosin 4, 8mg, or terazosin 2-10mg daily for 8 weeks and celecoxib 200mg daily for 8 weeks; Other Names: tamsulosin and celecoxib; alfuzosin and celecoxib; doxazosin and celecoxib; terazosin and celecoxib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The changes of International Prostatic Symptom Scores after medications	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Complications	During all study periods
The changes of voiding frequencies after medications	8 weeks
The changes of 'ICS male questionnaire-short form' after medications	8 weeks
Patient perception of treatment benefit questionnaire	8 weeks
The changes of 'patient perception of bladder condition' after medications	8 weeks
The changes of maximum flow rate and postvoid residuals after medications	8 weeks
The changes of serum PSA levels after medications	8 weeks
The changes of WBC counts on the expressed prostatic secretions after medications	8 weeks

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: The Korean Urological Association
• Investigators: Principal Investigator: Kyu-Sung Lee, Ph.D., M.D., Samsung Medical Center

Publications and helpful links

General Publications

• Kramer G, Steiner GE, Handisurya A, Stix U, Haitel A, Knerer B, Gessl A, Lee C, Marberger M. Increased expression of lymphocyte-derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation. Prostate. 2002 Jun 1;52(1):43-58. doi: 10.1002/pros.10084.
• Untergasser G, Madersbacher S, Berger P. Benign prostatic hyperplasia: age-related tissue-remodeling. Exp Gerontol. 2005 Mar;40(3):121-8. doi: 10.1016/j.exger.2004.12.008. Epub 2005 Jan 22.
• Lee KL, Peehl DM. Molecular and cellular pathogenesis of benign prostatic hyperplasia. J Urol. 2004 Nov;172(5 Pt 1):1784-91. doi: 10.1097/01.ju.0000133655.71782.14.
• Handisurya A, Steiner GE, Stix U, Ecker RC, Pfaffeneder-Mantai S, Langer D, Kramer G, Memaran-Dadgar N, Marberger M. Differential expression of interleukin-15, a pro-inflammatory cytokine and T-cell growth factor, and its receptor in human prostate. Prostate. 2001 Dec 1;49(4):251-62. doi: 10.1002/pros.10020.
• Kakehi Y, Segawa T, Wu XX, Kulkarni P, Dhir R, Getzenberg RH. Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia. Prostate. 2004 Jun 1;59(4):351-6. doi: 10.1002/pros.10365.
• Steiner GE, Newman ME, Paikl D, Stix U, Memaran-Dagda N, Lee C, Marberger MJ. Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate. 2003 Aug 1;56(3):171-82. doi: 10.1002/pros.10238.
• Wang W, Bergh A, Damber JE. Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate. 2004 Sep 15;61(1):60-72. doi: 10.1002/pros.20061.
• Kramer G, Marberger M. Could inflammation be a key component in the progression of benign prostatic hyperplasia? Curr Opin Urol. 2006 Jan;16(1):25-9.
• Rohrmann S, De Marzo AM, Smit E, Giovannucci E, Platz EA. Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey (NHANES III). Prostate. 2005 Jan 1;62(1):27-33. doi: 10.1002/pros.20110.
• Araki T, Yokoyama T, Kumon H. Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients with benign prostatic hyperplasia: a prospective non-randomized study of loxoprofen sodium 60 mg once daily before sleeping. Acta Med Okayama. 2004 Feb;58(1):45-9. doi: 10.18926/AMO/32115.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: May 27, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (Estimate): May 30, 2008

Study Record Updates

• Last Update Posted (Estimate): June 10, 2013
• Last Update Submitted That Met QC Criteria: June 7, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Treatment Outcome; Cyclooxygenase 2 Inhibitors; Alpha Blockers
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Inflammation; Prostatic Hyperplasia; Hyperplasia; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Peripheral Nervous System Agents; Urological Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Celecoxib; Tamsulosin; Alfuzosin; Prazosin; Doxazosin; Terazosin; Adrenergic alpha-Antagonists
• Other Study ID Numbers: 2006-07-084