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

Phase 4

Completed

Conditions: Bladder Outlet Obstruction

Interventions: Drug: Detrusitol 4 mg QD
Drug: Doxazosin 4 mg QD

Registration Number: NCT01661621

Lead Sponsor: Buddhist Tzu Chi General Hospital

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 395

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Detrusitol 4 mg QD	Antimuscarinics (Detrusitol 4 mg QD)
Group 2	Doxazosin 4 mg QD	α-blockers (Doxazosin 4 mg QD)

Primary Outcome Measures

Name	Time	Method
The Global Response Assessment (GRA) After the Treatment Day	1 month after initial treatment	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

Secondary Outcome Measures

Name	Time	Method
The International Prostate Symptom Score (IPSS) Questionnaires After the Treatment Day	Baseline and 1 month	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
The Maximum Flow Rate (Qmax) After the Treatment Day	Baseline and 1 month	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
The Voided Volume After the Treatment Day	Baseline and 1 month	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
The Postvoid Residual Volume (PVR) After the Treatment Day	Baseline and 1 month	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
The IPSS Subscore (IPSS Voiding) Questionnaires After the Treatment Day	Baseline and 1 month	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
The IPSS Subscore (IPSS Storage) Questionnaires After the Treatment Day	Baseline and 1 month	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
The International Prostate Symptom Score (IPSS) Quality of Life (QoL) Score After the Treatment Day	Baseline and 1 month	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