A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH). To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up. We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin. International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance. We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone. The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.

Gacci M ，Vittori G ，Tosi N ，Siena G ，Rossetti MA ，Lapini A ，Vignozzi L ，Serni S ，Maggi M ，Carini M ... -  《-》

A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction are common disorders of advancing age. To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH. In this prospective randomized study, 133 men complaining of LUTS due to BPH were included. Forty-five patients received tamsulosin 0.4 mg/day alone (Group A), 44 patients received tadalafil 10 mg/day (Group B), and combination therapy (tamsulosin and tadalafil both) was instituted in 44 patients (Group C). After a 2-week medication free run-in period, they were evaluated for International Prostatic Symptom Score (IPSS), International Index of Erectile Function score (IIEF5), quality of life (IPSS QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR) volume, and safety parameters before and at 3 months of treatment. There were primary (IPSS, IPSS QoL index, Qmax, and PVR) and secondary (erectile function [EF] domain scores from IIEF5) efficacy end points. Safety assessment included laboratory tests and patient's reporting of adverse event. A significant improvement in IPSS score was observed in all the 3 groups A, B, and C (-50.90%, P < 0.05; -33.50%, P < 0.05; and -53.90%, P < 0.05, respectively). IIEF5 score increased significantly in these three groups (+39.28%, P < 0.05; +45.96%, P < 0.05; and +60.23%, P < 0.05, respectively). A significant increase in Qmax and decrease in PVR were also observed (33.99%, P < 0.05; 29.78%, P < 0.05; and 37.04%, P < 0.05) and (-60.90%, P < 0.05; -49.45%, P < 0.05; and -62.97%, P < 0.05, respectively). The QoL scores improved significantly (-73.35%, P < 0.05; -70.26%, P < 0.05; and -79.65%, P < 0.05, respectively). Side effects were dyspepsia, heartburn, headache, flushing, myalgia, and backache. Adverse effect dropout was 3.7%. No participant experienced any severe or serious adverse events. In patients with LUTS due to BPH, tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS. Their EF also improves with these medications. The improvement is better with combination therapy compared with single agent alone.

Singh DV ，Mete UK ，Mandal AK ，Singh SK ... -  《-》

Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial.

Phosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). To assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED. A randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg. The primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24. The mean changes in total IPSS and IIEF-EF scores were -9.46 and 9.17 for FDC 0.4/5 mg and -8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period. The FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED. The study clearly demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower incidence of side effects, and the simplification and convenience of therapy, which led to better overall patient compliance. However, the lack of a tamsulosin monotherapy control group was a limitation of this study. The FDC 0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that combination therapy could provide clinical benefits for patients with BPH-associated LUTS complaints and ameliorate the comorbidity of ED. Kim SW, Park NC, Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. J Sex Med 2017;14:1018-1027.

Kim SW ，Park NC ，Lee SW ，Yang DY ，Park JK ，Moon DG ，Yang SK ，Lee SW ，Moon KH ，Ahn TY ，Kim SW ，Park K ，Min KS ，Ryu JK ，Son H ，Jung J ，Hyun JS ... -  《-》

A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Stief CG ，Porst H ，Neuser D ，Beneke M ，Ulbrich E ... -  《EUROPEAN UROLOGY》

Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial.

The prevalence of erectile dysfunction (ED) is increased in men with metabolic syndrome compared with the general population. The aim of this study was to evaluate the efficacy and safety of vardenafil vs. placebo in men who had ED and metabolic syndrome. This was a 12-week, double-blind, randomized, multicenter, parallel-group, placebo-controlled prospective study in men with ED and metabolic syndrome (assessed by the International Diabetes Federation criteria). Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks, depending on efficacy and tolerability. Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile (SEP) diary questions 2/3. Secondary efficacy measures included SEP1, a diary question assessing ejaculation, the percentage of men achieving "return-to-normal" erectile function, and the percentage of men who titrated to a different dose. Adverse events (AEs) were recorded throughout the study. The intent-to-treat population included 145 men (vardenafil, N = 75; placebo, N = 70). Baseline least squares IIEF-EF domain scores were low (vardenafil: 12.0; placebo: 12.7), indicative of moderate-to-severe ED. Vardenafil was statistically significantly superior to placebo for all primary efficacy measures (P < 0.0001) and showed nominally statistically significant superiority compared with placebo for SEP1/ejaculation success rates (P = 0.0003 and P < 0.0001, respectively) and the percentage of subjects reporting "return-to-normal" erectile function (P = 0.0004). Treatment-emergent AEs were mild-to-moderate in severity and consistent with the known AE profile of phosphodiesterase type 5 inhibitors. This is the first study to assess the efficacy and safety of vardenafil, taken alone, for ED therapy in a population of men who all had metabolic syndrome. Although baseline erectile function in these patients was low, vardenafil treatment was associated with significant improvements in erectile function and rates of successful intercourse, and was well tolerated.

Schneider T ，Gleissner J ，Merfort F ，Hermanns M ，Beneke M ，Ulbrich E ... -  《-》