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.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.
Jannini
Emmanuele A
EA
School of Sexology, Department of Experimental Medicine, University of L'Aquila, Coppito, L'Aquila, Italy. emmanuele.jannini@univaq.it
Isidori
Andrea M
AM
Gravina
Giovanni Luca
GL
Aversa
Antonio
A
Balercia
Giancarlo
G
Bocchio
Massimo
M
Boscaro
Marco
M
Carani
Cesare
C
Corona
Giovanni
G
Fabbri
Andrea
A
Foresta
Carlo
C
Forti
Gianni
G
Francavilla
Sandro
S
Granata
Antonio R M
AR
Maggi
Mario
M
Mansani
Riccardo
R
Palego
Pierfrancesco
P
Spera
Giovanni
G
Vetri
Mario
M
Lenzi
Andrea
A
D000704:Analysis of Variance; D002243:Carbolines / Q000627:therapeutic use*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D006306:Health Surveys; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D018783:Impotence, Vasculogenic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D012306:Risk; D000068677:Sildenafil Citrate; D013223:Statistics as Topic; D013450:Sulfones / Q000627:therapeutic use*; D000068581:Tadalafil; D013997:Time Factors; D014227:Triazines / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
D002243:Carbolines; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate