Intermittent (Every-Other-Day) vs Daily Tamsulosin for Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia (LUTS/BPH) : A Multicenter, Assessor-Blinded, Randomized Non-Inferiority Trial. Arab Randomized Assessment of BPH Treatment (ARAB Trial)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- Change in International prostate symptom score (IPSS) From Baseline to Week 24
研究概览
简要总结
Background:
Lower urinary tract symptoms (LUTS) are common in aging men, most often due to benign prostatic hyperplasia (BPH), and significantly impair quality of life. α1-adrenoceptor antagonists are first-line therapy, with tamsulosin being the most widely prescribed. However, ejaculatory dysfunction (EjD) is a frequent adverse effect that negatively affects adherence. Optimal dosing strategies that maintain urinary efficacy while reducing EjD are not well defined, and current guidelines provide no recommendations regarding alternate-day dosing.
Patients and Methods:
This multicenter, randomized, open-label, assessor-blinded, parallel-group, non-inferiority trial will enroll men aged ≥50 years with LUTS/BPH and baseline IPSS ≥8. Participants will be randomized 1:1 to receive tamsulosin 0.4 mg once daily or every other day for 24 weeks. The primary endpoint is change in International Prostate Symptom Score (IPSS) from baseline to Week 24. Non-inferiority will be concluded if the upper bound of the two-sided 95% confidence interval (CI) for the between-group difference in mean IPSS change (EOD - Daily) is ≤ +3 points.
The key secondary endpoint is change in Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) total score from baseline to Week 24, tested for superiority only if IPSS non-inferiority is established. Additional secondary endpoints include maximum urinary flow rate (Qmax), post-void residual volume (PVR), IPSS-Quality of Life score, and ejaculatory adverse-event rates.
Sample Size and Analysis:
Assuming an SD of 6 for IPSS change, a non-inferiority margin of +3, one-sided α of 0.025, and 90% power, approximately 85 evaluable patients per arm are required for the primary endpoint. To ensure adequate power for EjD outcomes and allow for 20% attrition, 144 participants per arm (288 total) will be randomized. Analyses will follow the intention-to-treat principle with per-protocol sensitivity analyses. Primary inference will use ANCOVA or MMRM adjusted for baseline score, age, and study site, with multiple imputation for missing data.
Expected Outcomes:
This trial will provide the first adequately powered multicenter evidence on whether every-other-day tamsulosin preserves non-inferior LUTS control while improving ejaculatory outcomes, potentially supporting a simple and cost-effective strategy to enhance tolerability and adherence in men with LUTS/BPH.
详细描述
Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are commonly treated with α1-adrenoceptor antagonists, with tamsulosin being among the most frequently prescribed agents. Although effective for symptom relief, tamsulosin is associated with ejaculatory dysfunction, which may negatively affect treatment satisfaction and adherence. Despite long-standing clinical use, optimal dosing strategies that preserve urinary efficacy while reducing ejaculatory adverse effects remain insufficiently studied. Existing investigations of dose reduction or alternate-day regimens have been limited by small sample size, short follow-up, single-center design, and non-standardized assessment of sexual outcomes. Consequently, international guidelines do not currently recommend every-other-day dosing.
This multicenter, randomized, open-label, assessor-blinded, parallel-group, non-inferiority trial is designed to evaluate whether every-other-day tamsulosin dosing maintains non-inferior improvement in urinary symptoms while offering superior ejaculatory outcomes compared with standard daily dosing. Following a 4-week open-label run-in period with daily tamsulosin, participants demonstrating a predefined clinical response without safety concerns will be randomized in a 1:1 ratio to continue daily dosing or switch to every-other-day dosing for 24 weeks. Randomization will be centralized, computer-generated, and stratified by study site and baseline symptom severity.
After randomization, participants and treating clinicians will be aware of treatment allocation; however, outcome assessors and statisticians will remain blinded to minimize assessment and analytical bias. Study visits and assessments will be standardized across centers, and participants will be instructed not to disclose allocation status to assessors.
Efficacy assessments will include patient-reported symptom scores, objective voiding parameters, and validated sexual function questionnaires collected at prespecified intervals during follow-up. Safety monitoring will include adverse events, orthostatic vital signs, and treatment adherence throughout the study period.
The primary objective is to demonstrate non-inferiority of every-other-day dosing compared with daily dosing for improvement in urinary symptoms over 24 weeks, using a predefined non-inferiority margin based on established clinical relevance. A hierarchical testing strategy will be applied to evaluate superiority for ejaculatory function outcomes only if non-inferiority for urinary symptom control is established. Statistical analyses will follow the intention-to-treat principle with supportive per-protocol analyses, using appropriate regression models adjusted for baseline values and study site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
After allocation, both investigators and participants will be aware of the assigned dosing regimen (open-label). To minimize bias, all efficacy assessments (e.g., IPSS, uroflowmetry, and PVR) will be conducted by trained assessors who are blinded to treatment allocation and not involved in clinical management or drug dispensing.
Study statisticians will remain blinded to treatment identity until the database is locked and the primary analysis completed. Any instance of unintentional unblinding will be documented, along with its rationale and potential impact on the study outcome.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •• Men ≥40 years with LUTS/BPH.
- •IPSS ≥8, Qmax 5-15 mL/s (voided volume ≥150 mL), PVR <200 mL.
- •Sexually active within the past month (for ejaculatory outcomes).
- •BPH-treatment naïve: no prior use of antimuscarinics or 5-α-reductase inhibitors (5-ARIs) and agrees not to initiate these agents during the trial.
排除标准
- •• PVR ≥ 200 mL.
- •Prior prostate/ radical pelvic surgery (that affect pelvic innervation).
- •Neurogenic bladder (atonic/ hypotonic bladder).
- •Severe hepatic/renal insufficiency.
- •Significant cardiovascular or cerebrovascular disease.
- •Any indication of surgical treatment (vesical stones, chronic urine retention, recurrent attacks of acute urine retention, recurrent attacks of gross hematuria, hydronephrosis)
研究组 & 干预措施
Daily arm: Tamsulosin 0.4 mg once daily.
干预措施: Daily Tamsulosin (Drug)
EOD arm: Tamsulosin 0.4 mg every other day (no capsule on off-days)
干预措施: Intermittent Tamsulosin (Drug)
结局指标
主要结局
Change in International prostate symptom score (IPSS) From Baseline to Week 24
时间窗: Baseline to Week 24
Change in the International Prostate Symptom Score (IPSS) from baseline to Week 24. The IPSS is a validated 7-item questionnaire assessing lower urinary tract symptoms, with total scores ranging from 0 to 35, where higher scores indicate more severe symptoms. This is a non-inferiority comparison with a non-inferiority margin of +3 IPSS points. Non-inferiority will be concluded if the upper bound of the two-sided 95% confidence interval for the between-group difference in mean IPSS change (Intermittent - Daily) is ≤ +3 points.
次要结局
- Change in MSHQ-Ejaculatory Dysfunction Total Score From Baseline to Week 24(Baseline to Week 24)
研究者
Mahmoud Laymon
Prof.
Mansoura University