A 52‐week multicenter randomized controlled study of the efficacy and safety of add‐on dutasteride and imidafenacin to tamsulosin in patients with benign prostatic hyperplasia with remaining overactive bladder symptoms (DIrecT study)

Abstract

Objective: The aim of this study was to examine the long-term efficacy of combination of tamsulosin 0.2 mg + dutasteride 0.5 mg + imidafenacin 0.2 mg (TDI) therapy compared with tamsulosin + dutasteride (TD) therapy for 52 weeks in benign prostatic hyperplasia (BPH) patients with a prostate volume (PV) ≥30 mL and remaining overactive bladder (OAB) symptoms after having received tamsulosin for ≥8 weeks. Previously, we reported that the improvement in OAB symptoms at 24 weeks was significantly greater in the TDI than TD group.Methods: BPH patients with OAB symptoms after ≥8 weeks tamsulosin were randomly assigned to the TDI or TD group in a ratio of 1:1 ratio, and followed-up for 52 weeks. Changes in the OAB Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and postvoid residual (PVR) were evaluated.Results: In all, 163 patients were randomized, and 125 patients (76.7%) completed 52 weeks of treatment. At Week 52, there were significant decreases in the OABSS and IPSS storage subscore compared with baseline in the TDI versus TD group, but the change in the total IPSS did not differ significantly between the two groups. There was no change in PVR from Week 24 toWeek 52 in either group.Conclusions: For BPH patients with PVR ≥30 mL and remaining storage symptoms despite tamsulosin monotherapy, TDI treatment showed better results in terms of improved OAB symptoms than TD treatment up to 52 weeks. K E Y W O R D S5α-reductase inhibitor, benign prostatic hyperplasia, cholinergic antagonist, combination therapy, long-term efficacy, overactive bladder

A randomized controlled study of the efficacy of tadalafil monotherapy versus combination of tadalafil and mirabegron for the treatment of persistent overactive bladder symptoms in men presenting with lower urinary tract symptoms (CONTACT Study)

“…For the treatment of “LUTS/BPH” with large prostate (prostate volume >30 mL), the combination of an α‐blocker and a 5α‐reductase inhibitor (dutasteride) has been reported to be more effective, even in the storage symptoms, compared to each monotherapy 16,17 . However, the combination of α‐blocker, dutasteride, and anticholinergic drug has been reported to be more effective than the combination of α‐blocker plus dutasteride for the treatment of “BPH/OAB” with large prostate (DIrecT study) 18,19 …”

“…16,17 However, the combination of α-blocker, dutasteride, and anticholinergic drug has been reported to be more effective than the combination of α-blocker plus dutasteride for the treatment of "BPH/OAB" with large prostate (DIrecT study). 18,19 The purpose our study is to evaluate whether the combination of tadalafil and mirabegron is more effective than monotherapy with tadalafil in men with remaining OAB symptoms despite monotherapy with tadalafil. Thus, we recruited patients who had been taking tadalafil monotherapy but had remaining OAB symptoms.…”

“…And there are many good quality RCTs without placebo. 3,5,7,[16][17][18][19] Although this study was not double-blinded using placebo, the quality of this study seemed considerable because randomization and analyses of data were strictly centrally organized and computer-based.…”

Meta-Analysis of the Efficacy and Safety of Imidafenacin for Overactive Bladder Induced by Benign Prostatic Hyperplasia in Men Receiving Alpha-Blocker Therapy

“…Therefore, high anticholinergic doses damage bladder contractility. Furthermore, compared with alpha-blocker monotherapy, add-on imidafenacin treatment showed better results in terms of improvements in OAB symptoms for BPH patients in a long-term evaluation [ 38 ]. Of course, much more research is needed to demonstrate the above points conclusively.…”

Triple Therapy with Tamsulosin, Dutasteride, and Imidafenacin for Benign Prostatic Hyperplasia in Patients with Overactive Bladder Symptoms Refractory to Tamsulosin: Subgroup Analyses of the DIrecT Study

“…The results of the DIrecT study, a 52-week multicenter, randomized, open-label, controlled trial, have been reported elsewhere [1,3]. In summary, patients with BPH (prostate volume ≥30 mL), aged ≤50 and <90 years, with OAB symptoms (total OABSS ≥3 and OABSS urgency subscore ≥2) after tamsulosin administration for ≥8 weeks were randomly assigned to the TDI group or the TD group at a 1:1 ratio and followed for 52 weeks.…”