Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Prostatic Hyperplasia

Hyperplasia

Lower Urinary Tract Symptoms

Prostatic Diseases

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Antihypertensive Agents

Celecoxib

Doxazosin

Cyclooxygenase 2 Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Adrenergic Agents

Adrenergic alpha-1 Receptor Antagonists

Adrenergic alpha-Antagonists

Adrenergic Antagonists

Neurotransmitter Agents

Doxazosin 4 mg daily plus celecoxib 200 mg every day (QD)

Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD)

Doxazosin 4 mg every day (QD)

Hann-Chorng Kuo, M.D.

To investigate the therapeutic effect and safety of celecoxib adding on doxazosin and the potential predictive value of the absence of prostate cancer in the treatment of patients with LUTS/BPH and an elevated serum PSA level.

Patients who meet all eligible requirements for entry into the study will be randomized into one of the two treatment groups for 3 months in 2:1 ratio as shown below:

1. Doxazosin 4 mg daily plus celecoxib 200 mg every day (QD)
2. Doxazosin 4mg every day (QD)

Study Procedure

* Male patients aged 40 years or older, having LUTS for at least 3 months (IPSS ≥ 8), a serum PSA level ≥ 4 ng/mL, without a palpable prostatic nodule will be enrolled into this prospective randomized trial to investigate whether COX-2 inhibitor can decrease serum PSA level and acts as a biomarker to differentiate between chronic inflammation and prostate cancer.
* Eligible subjects will be randomly assigned to the study and control groups at 2:1 ratio. The study group will receive doxazosin 4mg every day (QD) plus celecoxib 200mg QD for 3 months and the control group will receive doxazosin 4 mg QD for 3 months. Patients will be investigated for IPSS, total prostatic volume, transition zone index, maximum flow rate, voided volume, postvoid residual, serum PSA, free PSA and serum C-reactive protein (CRP) levels at baseline and 3 months after treatment. If the serum PSA levels remained higher than 4 ng/mL, patients of either group will be advised to receive prostatic biopsy for histopathological investigation.
* The prostatic biopsy will be advised at the end of the study in both groups of patients. Ten prostatic biopsied strips will be sent to pathological department for investigating the existence of prostatic cancer. The other two strips will be stored in liquid nitrogen for further investigation of inflammatory biomarkers.

Data Analysis

* The efficacy evaluation will be performed on intention-to-treat populations (ITT) and per-protocol populations (PPP) datasets while the safety evaluation will be performed on ITT datasets. The primary conclusion will be made for the primary endpoint and secondary endpoint on the ITT population.

Efficacy Endpoint Analysis

* Net change of each efficacy item will be analyzed by paired t-test between baseline and post-treatment in the treatment group and controlled group. The net changes of each efficacy item will be analyzed by ANOVA test to compare between treatment group and controlled group. The global assessment by the patients will be analyzed by chi-square test between the treatment and controlled group.
* All efficacy variables will be reported of respective point estimated and 95% confidence interval. Comparison tests will be reported of respective p value.

Safety Endpoints

* Adverse events will be reported by both controlled and treatment groups and by physiological systems as appropriate. Incidence of adverse events and the categories of adverse event severity between treatments will be analyzed by Cochran-Mantel-Haenszel test. The coding system used will be the Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART).

Changes in physical examinations will be displayed for each individual system.

* All statistical tests used will be two-tailed with α= 0.05.

Expected Results and Conclusion

* Chronic inflammation has been considered a possible but important factor to induce LUTS and promote prostatic growth. PSA elevation is a sensitive but not specific sign for prostatic cancer. In order to reduce the need for prostatic biopsy in patients with an elevated serum PSA level, the results of this study might provide a simple way for initial differential diagnosis of chronic inflammation from prostatic cancer. If serum PSA can be reduced significantly after celecoxib therapy and the positive biopsy rate of the following prostatic biopsy is lower than the control group, we might use this treatment for the initial management of high PSA level in men with LUTS/BPH. Furthermore, if chronic inflammation of the prostate can be reduced, the bothersome of the LUTS as well as voiding condition might be improved. This result can be another benefit for men who are suffering from LUTS and worried about surgical intervention.

Cyclooxygenase-2 (COX-2) Inhibitor Reduces Serum Prostatic Specific Antigen (PSA) Levels

COX-2 Inhibitor Reduces Serum PSA Levels Might Predict a Lower Risk of Prostatic Cancer in Men With LUTS/BPH With an Elevated PSA Level

Efficacy:

Change from Baseline in the serum PSA level from baseline and 3 months Change = Month 3 minus Baseline value

Efficacy:

Change from Baseline in the Void Volume (VV) from baseline and 3 months Change = Month 3 minus Baseline value

Efficacy:

Change from Baseline in the maximum flow rate (Qmax) from baseline and 3 months Change = Month 3 minus Baseline value

Efficacy:

Change from Baseline in the IPSS Voiding from baseline and 3 months. The IPSS subscore (IPSS Voiding) questionnaires is a 4 symptom questions. The symptom score have 6-point scale ranging from 0 "Not at all" to 5 "Almost always". Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom.

The total IPSS Voiding score can therefore range from 0 to 20 (asymptomatic to very symptomatic).

Change = Month 3 minus Baseline value

Efficacy:

Change from Baseline in the IPSS Storage from baseline and 3 months The IPSS subscore (IPSS Storage) is a 3 symptom questions. The symptom score have 6-point scale ranging from 0 "Not at all" to 5 "Almost always". Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom.

The total IPSS Storage score can therefore range from 0 to 15 (asymptomatic to very symptomatic).

Change = Month 3 minus Baseline value

Efficacy:

Change from Baseline in the International Prostate Symptom Score (IPSS) from baseline and 3 months The International Prostate Symptom Score (IPSS) is an 7 symptom questions including 4 voiding questions (IPSS Voiding), 3 storage questions (IPSS Storage) The symptom score have 6-point scale ranging from 0 "Not at all" to 5 "Almost always".

Total IPSS score = IPSS voiding + IPSS Storage Rang = 0 to 35 (asymptomatic to very symptomatic). Mild = 0 to 7; Moderate = 8 to 19; Severe = 20 to 35

Change = Month 3 minus Baseline value

Buddhist Tzu Chi General Hospital

Department of Urology

No patient suffered from heart attack, stroke, thromboembolic events or peptic ulcer. No adverse event related to the test medications was observed.

Study Group

Control Group

Doxazosin 4 mg daily plus celecoxib 200 mg daily, complete 3 month therapy N=64(91.4%)

Doxazosin 4 mg alone everyday, complete 3 month therapy N=58(82.9%)

Total

Age, Continuous

Sex: Female, Male

Taiwan

Region of Enrollment

Dr. Hann-Chorng Kuo

Baseline

3 months

Change

Change From Baseline in the Serum Prostate Specific Antigen (PSA) Level

Change From Baseline in the Void Volume (VV)

Change From Baseline in the Maximum Flow Rate (Qmax)

Change From Baseline in the IPSS Subscore (IPSS Voiding) Questionnaires

Change From Baseline in the IPSS Subscore (IPSS Storage) Questionnaires

Change From Baseline in the International Prostate Symptom Score (IPSS) Questionnaires

Completed the 3-month Therapy

PSA >4 ng/dL at 3 Months

Prostate Biopsy at 3 Months

Spots Global Cancer Trial Database for doxazosin 4 mg every day (qd)