Antimuscarinics as the First-line Treatment for Male With IPSS-V/S≤1

Bladder Outlet Obstruction Clinical Trial

Official title:

Antimuscarinics as the First-line Treatment for Male With International Prostate Symptom Score (IPSS) Voiding-to-storage Subscore Rati (IPSS-V/S)≤1-- A Prospective Randomized Study Comparing With α-blockers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01661621
• Other study ID #: TCGHUROL002
• Status: Completed
• Phase: Phase 4
• First received: August 2, 2012
• Last updated: June 23, 2014
• Start date: August 2012
• Est. completion date: August 2013

Study information

• Verified date: June 2014
• Source: Buddhist Tzu Chi General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of HealthTaiwan: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study is a prospective randomized, open label, controlled, double arm, post-marketing study to compare the treatment efficacy of first-line antimuscarinics and α-blockers monotherapy for men with moderate to severe lower urinary tract symptoms (LUTS) (International Prostate Symptom Score (IPSS-T) ≥8) and IPSS voiding-to-storage subscore ratio (IPSS-V/S) ≤1.

Description:

1. STUDY PROCEDURE

1.1.General Study Design This study is a prospective randomized, open label, controlled, double arm, post-marketing study to compare the treatment efficacy of first-line antimuscarinics and α-blockers monotherapy for men with moderate to severe LUTS (IPSS-T ≥8) and IPSS-V/S ≤1.

1.2. Study Visits and Evaluations

1.2.1 Screening Visit (Baseline, 1 day to 1 week of the first treatment day).

1.2.1.1 Explain the nature of the study and have patients to read and sign an Informed Consent Form.

1.2.1.2 Screen patients for inclusion/exclusion criteria. 1.2.1.3 Medical History of lower urinary tract symptoms and previous treatment modalities.

1.2.1.4 Vital signs monitoring, general physical examinations of all systems (including digital rectal examination), serum prostatic specific antigen (PSA), and urinalysis.

1.2.1.5 Record Patient Perception of Bladder Condition (PPBC), IPSS (IPSS-T, IPSS voiding (IPSS-V), and IPSS storage (IPSS-S)), Overactive Bladder Symptom Score (OAB-SS), and quality of Life index (QoL-I)scores.

1.2.1.6 Obtain maximum flow rate (Qmax), voided volume, postvoid residual volume (PVR), total prostate volume (TPV), and transitional zone index (TZI).

1.2.1.7 Randomized assigned patients into 2 groups; men in one group received Doxazosin 4 mg QD, and those in the other group received Detrusitol 4 mg QD.

1.2.2 First Evaluation Visit (2 weeks after the initial treatment) 1.2.2.1 Vital signs monitoring and record adverse events. 1.2.2.2 Record PPBC, IPSS (IPSS-T, IPSS-V, IPSS-S), OAB-SS and QoL. 1.2.2.3 Check urinalysis for urinary tract infection if patient has symptoms suggestive of urinary tract infection.

1.2.2.4 Check Qmax, voided volume, and PVR.

1.2.3 Second Evaluation Visit (4 weeks after the treatment). 1.2.3.1 Vital signs monitoring and record adverse events. 1.2.3.3 Check urinalysis for urinary tract infection if patient has symptoms suggestive of urinary tract infection.

1.2.3.4 Check Qmax, voided volume, and PVR.

1.2.4 Third Evaluation Visit (3 months after the treatment). 1.2.4.1 Vital signs monitoring and record adverse events. 1.2.4.2 Record PPBC, IPSS (IPSS-T, IPSS-V, IPSS-S), OAB-SS and QoL. 1.2.4.3 Check urinalysis for urinary tract infection if patient has symptoms suggestive of urinary tract infection.

1.2.4.4 Check Qmax, voided volume, and PVR.

1.3. Withdrawal Criteria

Patients with any of the following conditions may be withdrawn from the trial:

1.3.1. Patients decide to withdraw their consent. 1.3.2. Patients indicate the status of lack of efficacy which is of clinical significance judged by the investigators that may lead to permanent damage to the patients.

1.3.3. Investigators consider that there is of safety concerns for the patients to remain in the trial (such as development severe medical disease).

1.3.4. Lost of follow-up or death. 1.3.5. PVR≥300 mL

1.4. Concomitant Treatments Investigator will try to minimize the concomitant medications for the patients during the trial duration. However, patients are allowed to continue taking stable medication in stable dose for diseases other than genitourinary system.

1.5. Prohibited medication

Patients are not allowed to take any of the following medications during the study:

1. Anticholinergics other than test drug

2. Alpha-adrenergic receptor blockers

3. Tricyclic anti-depressants

4. Calcium channel blockers

5. Skeletal muscle relaxant

6. Cyclooxygenase-2 (COX-2) inhibitors

Recruitment information / eligibility

• Status: Completed
• Enrollment: 395
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Men aged =40 years with lower urinary tract symptoms (IPSS =8)

• Patient or his/her 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 urinary retention, urodynamically proven detrusor underactivity or PVR =250 mL

• Patients with known active urinary tract infection, urinary stone or malignancy

• Patients with history of urethral injury or transurethral surgery for prostate or bladder

• 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

• Patients with major psychiatric illness or drug abuse

• Patients taken medication such as alpha-blocker, antimuscarinic or 5 alpha-reductase (5AR) inhibitor within 6 months

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Outlet Obstruction
• Urinary Bladder Neck Obstruction

Intervention

Drug:
• Detrusitol 4 mg QD
Group 1
• Doxazosin 4 mg QD
Group 2

Locations

Country	Name	City	State
Taiwan	Buddhist Tzu Chi General Hospital	Hualien

Sponsors (1)

Lead Sponsor	Collaborator
Buddhist Tzu Chi General Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (16)

Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):167-78. — View Citation

Athanasopoulos A, Chapple C, Fowler C, Gratzke C, Kaplan S, Stief C, Tubaro A. The role of antimuscarinics in the management of men with symptoms of overactive bladder associated with concomitant bladder outlet obstruction: an update. Eur Urol. 2011 Jul;60(1):94-105. doi: 10.1016/j.eururo.2011.03.054. Epub 2011 Apr 9. Review. — View Citation

Athanasopoulos A, Gyftopoulos K, Giannitsas K, Fisfis J, Perimenis P, Barbalias G. Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study. J Urol. 2003 Jun;169(6):2253-6. — View Citation

Blake-James BT, Rashidian A, Ikeda Y, Emberton M. The role of anticholinergics in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a systematic review and meta-analysis. BJU Int. 2007 Jan;99(1):85-96. Epub 2006 Oct 9. Review. — View Citation

Chapple C. Antimuscarinics in men with lower urinary tract symptoms suggestive of bladder outlet obstruction due to benign prostatic hyperplasia. Curr Opin Urol. 2010 Jan;20(1):43-8. doi: 10.1097/MOU.0b013e3283330862. Review. — View Citation

Chapple CR, Roehrborn CG. A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder. Eur Urol. 2006 Apr;49(4):651-8. Epub 2006 Feb 17. Review. — View Citation

Chung DE, Te AE, Staskin DR, Kaplan SA. Efficacy and safety of tolterodine extended release and dutasteride in male overactive bladder patients with prostates >30 grams. Urology. 2010 May;75(5):1144-8. doi: 10.1016/j.urology.2009.12.010. Epub 2010 Mar 5. — View Citation

Chung SD, Chang HC, Chiu B, Liao CH, Kuo HC. The efficacy of additive tolterodine extended release for 1-year in older men with storage symptoms and clinical benign proastatic hyperplasia. Neurourol Urodyn. 2011 Apr;30(4):568-71. doi: 10.1002/nau.20923. Epub 2011 Feb 22. — View Citation

Djavan B, Margreiter M, Dianat SS. An algorithm for medical management in male lower urinary tract symptoms. Curr Opin Urol. 2011 Jan;21(1):5-12. doi: 10.1097/MOU.0b013e32834100ef. Review. — View Citation

Kaplan SA, McCammon K, Fincher R, Fakhoury A, He W. Safety and tolerability of solifenacin add-on therapy to alpha-blocker treated men with residual urgency and frequency. J Urol. 2009 Dec;182(6):2825-30. doi: 10.1016/j.juro.2009.08.023. Epub 2009 Oct 17. — View Citation

Kaplan SA, Roehrborn CG, Abrams P, Chapple CR, Bavendam T, Guan Z. Antimuscarinics for treatment of storage lower urinary tract symptoms in men: a systematic review. Int J Clin Pract. 2011 Apr;65(4):487-507. doi: 10.1111/j.1742-1241.2010.02611.x. Epub 2011 Jan 7. Review. — View Citation

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28. Erratum in: JAMA. 2007 Mar 21:297(11):1195. JAMA. 2007 Oct 24;298(16):1864. — View Citation

Lee JY, Kim HW, Lee SJ, Koh JS, Suh HJ, Chancellor MB. Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder. BJU Int. 2004 Oct;94(6):817-20. — View Citation

Liao CH, Chung SD, Kuo HC. Diagnostic value of International Prostate Symptom Score voiding-to-storage subscore ratio in male lower urinary tract symptoms. Int J Clin Pract. 2011 May;65(5):552-8. doi: 10.1111/j.1742-1241.2011.02638.x. — View Citation

Martín-Merino E, García-Rodríguez LA, Massó-González EL, Roehrborn CG. Do oral antimuscarinic drugs carry an increased risk of acute urinary retention? J Urol. 2009 Oct;182(4):1442-8. doi: 10.1016/j.juro.2009.06.051. Epub 2009 Aug 15. — View Citation

McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, Foster HE Jr, Gonzalez CM, Kaplan SA, Penson DF, Ulchaker JC, Wei JT. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011 May;185(5):1793-803. doi: 10.1016/j.juro.2011.01.074. Epub 2011 Mar 21. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Global Response Assessment (GRA) After the Treatment Day	Efficacy Using global response assessment (GRA) to compare the efficacy in Group 1 and Group 2 from baseline to 1month.; The global response assessment on a 6-point scale ranging from 1 "No problems at all" to 6 "Many severe problems".; Changes of the global response assessment (GRA) improved or reduction by 1 points.; Change = Baseline minus Month 1 value; Safety: Systemic adverse events such as difficult urination, dry mouth, dry eye, blurred vision, constipation, dizziness or general weakness	1 month after initial treatment	Yes
Secondary	The International Prostate Symptom Score (IPSS) Questionnaires After the Treatment Day	Efficacy: Using the total International Prostate Symptom Score (IPSS) to compare the efficacy in Group 1 and Group 2 from baseline to 1 month.; 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; Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes
Secondary	The Maximum Flow Rate (Qmax) After the Treatment Day	Efficacy: Net change used the the maximum flow rate (Qmax) in Group 1 and Group 2 from baseline to 1 month.; Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes
Secondary	The Voided Volume After the Treatment Day	Efficacy: Net change used the the voided volume in Group 1 and Group 2 from baseline to 1 month.; Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes
Secondary	The Postvoid Residual Volume (PVR) After the Treatment Day	Efficacy: Net change used the the postvoid residual volume (PVR) in Group 1 and Group 2 from baseline to 1 month.; Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes
Secondary	The IPSS Subscore (IPSS Voiding) Questionnaires After the Treatment Day	Efficacy: Using the the IPSS subscore (IPSS Voiding) questionnaires to compare the efficacy in Group 1 and Group 2 from baseline to 1 month.; 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).; Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes
Secondary	The IPSS Subscore (IPSS Storage) Questionnaires After the Treatment Day	Efficacy: Using the the IPSS subscore (IPSS Storage) to compare the efficacy in Group 1 and Group 2 from baseline to 1 month.; 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).; Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes
Secondary	The International Prostate Symptom Score (IPSS) Quality of Life (QoL) Score After the Treatment Day	Efficacy: Using the the the International Prostate Symptom Score (IPSS) quality of life (QoL) score to compare the efficacy in Group 1 and Group 2 from baseline to 1month.; The IPSS quality of life question score on a 7-point scale ranging from 0 "Delighted" to 6 "Terrible".; IPSS-QoL ranges 0 to 6 (Delighted to Terrible); Safety: Systemic adverse events such as difficult urination, dry mouth, blurred vision, constipation, dry eye, dizziness, or general weakness	Baseline and 1 month	Yes