Efficacy and Safety of Mirabegron and Tamsulosin Combination Therapy Compared to Tamsulosin Monotherapy for Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Results of a Multicenter, Randomized, Double-Blind, Phase III Clinical Trial

Abstract

Purpose: This study aimed to evaluate the efficacy and safety of mirabegron and tamsulosin combination therapy compared to tamsulosin monotherapy in benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS). Materials and Methods: This phase 3, randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of mirabegron/tamsulosin combination therapy versus tamsulosin monotherapy in men with LUTS. The trial, conducted across 25 centers from July 2021 to October 2023. Eligible participants were randomly assigned to either the combination or monotherapy group for 12 weeks. Primary efficacy endpoints included changes in total urinary frequency score (TUFS) and International Prostate Symptom Scores (IPSS), with secondary endpoints evaluating various urinary symptoms and changes in post void residual volume (PVR), maximum urinary flow rate (Qmax), and quality of life scores. Safety assessments included adverse events, PVR, Qmax, vital signs, electrocardiogram, and laboratory tests. Results: A total of 795 participants were randomized to monotherapy (n=397) and combination therapy (n=398) groups. After 12 weeks, 342 in the monotherapy and 339 in the combination therapy group completed the study, with no significant baseline differences. The combination therapy group showed a greater improvement in TUFS (-11.28) and IPSS (-10.85) scores compared to monotherapy (-8.30 and-9.85, respectively) with significant differences (p<0.0001, p=0.0325). Combination therapy showed significant improvements in storage symptoms and voiding diary variables, including daytime frequency, urgency, and incontinence, compared to monotherapy. The incidence of treatment-emergent adverse events was similar between the groups (13.10% vs 16.58%, p=0.1943), with no serious drug-related adverse events, confirming an acceptable safety profile for combination therapy. Conclusions: Combination therapy with mirabegron and tamsulosin is more effective than monotherapy in improving LUTS in patients with BPH, particularly storage symptoms, with a comparable safety profile. A fixed-dose combination formulation in the future may further improve patient adherence and quality of life.