The ENDOTRIAL Study: A Spontaneous, Open-Label, Randomized, Multicenter, Crossover Study on the Efficacy of Sildenafil, Tadalafil, and Vardenafil in the Treatment of Erectile Dysfunction

Abstract

Introduction The three effective, commercially available drugs for the treatment of erectile dysfunction—sildenafil, vardenafil, and tadalafil—inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date. Aim The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen. Methods This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg. Main Outcome Measures The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment. Results In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI significantly ameliorated in patients receiving 100 mg of sildenafil. Regression analysis confirmed an independent effect of sildenafil on hemodynamic efficacy parameters. Conclusions An overall equivalence was demonstrated in the subjective perception of treatment benefits for all the PDE5i tested. However, sildenafil, in a dose-dependent manner, was the unique PDE5i able to ameliorate some of the penile flow parameters within the 8-week treatment period. These findings should be interpreted conservatively because of the observational nature of the study.

The SIAMS-ED Trial: A National, Independent, Multicentre Study on Cardiometabolic and Hormonal Impairment of Men with Erectile Dysfunction Treated with Vardenafil

“…The efficacy and safety of vardenafil have been tested in several randomized trials, including men with various underlying conditions [25, 59–63]. All these studies documented efficacy that was retained irrespective of the medication used to treat the underlying disorders.…”

“…Sponsored clinical trials for drug registration purposes are often biased by the tendency to recruit populations with lower CVRs than seen in end users in a real-life setting [25]. Therefore, the safety and efficacy of PDE5i in high CV risk populations require further investigation.…”

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)

“…2 Patients using different PDE5 inhibitors have a similar perception of improvement after treatment. 245 Direct comparative studies are lacking and preference studies are inconclusive and biased. 246 In any case, patients should be given the opportunity to try different PDE5 inhibitors.…”

Sexual dysfunction in the older man

“…A recent prospective, randomized, multicentre crossover study demonstrated an overall equivalence in the subjective perception of treatment benefits between all PDE5I, although patients and their partners may have individual preferences. 47 Adverse events from PDE5I include headache, facial flushing, nasal congestion, myalgia, back pain and blurred or disturbed vision; these effects are generally attributed to cross-reactivity with other PDE isoforms. The nature and frequency of adverse events are similar in patients older than 65 years compared with their younger counterparts.…”