Clinical trial NCT01678313: Cyclooxygenase-2 (COX-2) Inhibitor Reduces Serum Prostatic Specific Antigen (PSA) Levels
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Benign Prostatic Hyperplasia
Keywords: Benign prostatic hyperplasia (BPH)
Lower urinary tract symptoms (LUTS)
Prostatic specific antigen (PSA)
Cyclooxygenase-2 (COX-2)
Lead sponsor: Buddhist Tzu Chi General Hospital
Sponsor class: OTHER
First posted: 2012-09-05
Enrollment: 140
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Male adults aged ≥ 40 years with LUTS/BPH, IPSS ≥ 8
* Free of active urinary tract infection
* Free of neurogenic voiding dysfunction
* No history of previous prostate biopsy within 6 months
* No treatment of BPH by alpha-blocker or 5-alpha-reductase inhibitor within 6 months
* Patient or his legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

* Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
* Patients with acute r chronic urinary retention and urodynamically proven detrusor underactivity
* Patients with postvoid residual \> 250 mL
* Patients have laboratory abnormalities at screening including:

  1. Aspartate aminotransferase (AST) \> 3 x upper limit of normal range
  2. Alanine aminotransferase (ALT) \> 3 x upper limit of normal range
  3. Patients have abnormal serum creatinine level \> 2 x upper limit of normal range
* Patients with any other serious disease or condition considered by the investigator not suitable for entry into the trial
* Patients participated investigational drug trial within 1 month before entering this study

Primary outcomes:
measure: Change From Baseline in the Serum Prostate Specific Antigen (PSA) Level
timeFrame: Baseline and 3 months after initial treatment
Secondary outcomes:
measure: Change From Baseline in the Void Volume (VV)
timeFrame: Baseline and 3 months after initial treatment
measure: Change From Baseline in the Maximum Flow Rate (Qmax)
timeFrame: Baseline and 3 months after initial treatment
measure: Change From Baseline in the IPSS Subscore (IPSS Voiding) Questionnaires
timeFrame: Baseline and 3 months after initial treatment
measure: Change From Baseline in the IPSS Subscore (IPSS Storage) Questionnaires
timeFrame: Baseline and 3 months after initial treatment
measure: Change From Baseline in the International Prostate Symptom Score (IPSS) Questionnaires
timeFrame: Baseline and 3 months after initial treatment
Other outcomes:
Locations:
city: Hualien
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
Study officials:
affiliation: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University
name: Hann-Chorng Kuo, M.D.
role: PRINCIPAL_INVESTIGATOR
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