AzTrials
AzTrials

Benign Prostatic HyperplasiaPhase 2NCT01678313

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

A Phase 2 study testing Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD) and Doxazosin 4 mg every day (QD) in people with Benign Prostatic Hyperplasia, run by Buddhist Tzu Chi General Hospital at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 40 years and older, men only
Conditions the study is for
Benign Prostatic Hyperplasia
What is being tested?
Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD) and Doxazosin 4 mg every day (QD)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
1 siteTaiwan
Study dates
Aug 2012to Aug 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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:
  • Aspartate aminotransferase (AST) > 3 x upper limit of normal range
  • Alanine aminotransferase (ALT) > 3 x upper limit of normal range
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

  • Buddhist Tzu Chi General Hospital

    Hualien City, 970

Other trials in Taiwan

About this study

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

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)
Read the 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.
Being tested
Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD), Doxazosin 4 mg every day (QD)
Keywords
Benign prostatic hyperplasia (BPH), Lower urinary tract symptoms (LUTS), Prostatic specific antigen (PSA), Cyclooxygenase-2 (COX-2)
Medical subject headings
Prostatic Hyperplasia, Lower Urinary Tract Symptoms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called Doxazosin 4 mg, Celecoxib 200 mg

    Study group

  • Doxazosin 4 mg every day (QD)Drug

    Also called Doxazosin 4 mg

    Control group

Study groups in NCT01678313
Study groupRoleWhat they receive
Study groupExperimentalDoxazosin 4 mg daily plus celecoxib 200 mg every day (QD)
Receives: Drug: Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD)
Control groupExperimentalDoxazosin 4 mg every day (QD)
Receives: Drug: Doxazosin 4 mg every day (QD)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Efficacy:

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

    Measured: Baseline and 3 months after initial treatment

Secondary outcomes (5)

  1. Change From Baseline in the Void Volume (VV)

    Efficacy:

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

    Measured: Baseline and 3 months after initial treatment

  2. Change From Baseline in the Maximum Flow Rate (Qmax)

    Efficacy:

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

    Measured: Baseline and 3 months after initial treatment

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

    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

    Measured: Baseline and 3 months after initial treatment

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

    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

    Measured: Baseline and 3 months after initial treatment

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

    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

    Measured: Baseline and 3 months after initial treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2012 (estimated)
  2. Study startAug 2012
  3. Primary completionAug 2013
  4. Study completionAug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01678313
Sponsor's protocol ID
TCGHUROL004
Status last verified
Jul 2014
First submitted
29 Aug 2012
Last updated
15 Jul 2014
Data monitoring committee
No

Publications

  • Liu HT, Kuo HC. Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology. 2008 Jul;72(1):104-8; discussion 108. doi: 10.1016/j.urology.2008.01.069. Epub 2008 Apr 8.

    PubMed 18400272

  • St Sauver JL, Sarma AV, Jacobson DJ, McGree ME, Lieber MM, Girman CJ, Nehra A, Jacobsen SJ. Associations between C-reactive protein and benign prostatic hyperplasia/lower urinary tract symptom outcomes in a population-based cohort. Am J Epidemiol. 2009 Jun 1;169(11):1281-90. doi: 10.1093/aje/kwp085. Epub 2009 Apr 24.

    PubMed 19395697

  • Andersson KE. LUTS treatment: future treatment options. Neurourol Urodyn. 2007 Oct;26(6 Suppl):934-47. doi: 10.1002/nau.20500.

    PubMed 17696154

  • Kuo HC. Videourodynamic analysis of pathophysiology of men with both storage and voiding lower urinary tract symptoms. Urology. 2007 Aug;70(2):272-6. doi: 10.1016/j.urology.2007.03.063.

    PubMed 17826488

  • Di Silverio F, Gentile V, De Matteis A, Mariotti G, Giuseppe V, Luigi PA, Sciarra A. Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis. Eur Urol. 2003 Feb;43(2):164-75. doi: 10.1016/s0302-2838(02)00548-1.

    PubMed 12565775

  • Sciarra A, Mariotti G, Salciccia S, Autran Gomez A, Monti S, Toscano V, Di Silverio F. Prostate growth and inflammation. J Steroid Biochem Mol Biol. 2008 Feb;108(3-5):254-60. doi: 10.1016/j.jsbmb.2007.09.013. Epub 2007 Sep 7.

    PubMed 17935971

  • Sciarra A, Di Silverio F, Salciccia S, Autran Gomez AM, Gentilucci A, Gentile V. Inflammation and chronic prostatic diseases: evidence for a link? Eur Urol. 2007 Oct;52(4):964-72. doi: 10.1016/j.eururo.2007.06.038. Epub 2007 Jul 2.

    PubMed 17618043

  • Alcaraz A, Hammerer P, Tubaro A, Schroder FH, Castro R. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur Urol. 2009 Apr;55(4):864-73. doi: 10.1016/j.eururo.2008.11.011. Epub 2008 Nov 21.

    PubMed 19027219

  • Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti Pannunzi L, Ciccariello M, Cardi A, Salvatori G, Sciarra A. Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Eur Urol. 2005 Jan;47(1):72-8; discussion 78-9. doi: 10.1016/j.eururo.2004.08.024.

    PubMed 15582252

  • Ozdemir I, Bozkurt O, Demir O, Aslan G, Esen AA. Combination therapy with doxazosin and tenoxicam for the management of lower urinary tract symptoms. Urology. 2009 Aug;74(2):431-5. doi: 10.1016/j.urology.2009.01.088. Epub 2009 Jun 7.

    PubMed 19501883

  • Jang J, Park EY, Seo SI, Hwang TK, Kim JC. Effects of intravesical instillation of cyclooxygenase-2 inhibitor on the expression of inducible nitric oxide synthase and nerve growth factor in cyclophosphamide-induced overactive bladder. BJU Int. 2006 Aug;98(2):435-9. doi: 10.1111/j.1464-410X.2006.06207.x.

    PubMed 16879691

  • Falahatkar S, Mokhtari G, Pourreza F, Asgari SA, Kamran AN. Celecoxib for treatment of nocturia caused by benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled study. Urology. 2008 Oct;72(4):813-6. doi: 10.1016/j.urology.2008.04.069. Epub 2008 Aug 9.

    PubMed 18692876

  • Djavan B, Waldert M, Zlotta A, Dobronski P, Seitz C, Remzi M, Borkowski A, Schulman C, Marberger M. Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study. J Urol. 2001 Sep;166(3):856-60.

    PubMed 11490233

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD) and Doxazosin 4 mg every day (QD) in people with Benign Prostatic Hyperplasia, run by Buddhist Tzu Chi General Hospital at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Serum Prostate Specific Antigen (PSA) Level (time frame: Baseline and 3 months after initial treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01678313, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in