Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo - and active-controlled clinical trial performed in Europe
Chapple Ch. R. Montorsi F. Tammela T. L.J. Wirth M. Koldewijn E. Fernandez Fernandez E.
1 Urology Department, Royal Hospital, Sheffield, UK; 2 Urology Department, Vita Salute San Raffaele University Hospital, Milan, Italy; 3 Urology Department, University of Tampere Hospital, Tampere, Finland; 4 Urology Department, Carl Gustav Carus University Hospital, Dresden, Germany ; 5 Urology Department, Catharina Hospital, Eindhoven, The Netherlands; 6 Urology Department, Ramin Kayal Hospital, Madrid, Spain
Background: Silodosin is a new selective therapy with a high pharmacologic selectivity for the a1A-adrenoreceptor.
Objective: Our aim was to test silodosin’s superiority to placebo and noninferiority to tamsulosin and discuss the findings in the context of a comprehensive literature review of the new compound silodosin.
Design, setting, and participants: We conducted a multicenter doubleblind, placebo-and active-controlled parallel group study. A total of 1228 men ≥50 yr of age with an International Prostate Symptom Score
(IPSS) ≤13 and a urine maximum flow rate (Qmax)>4 and ≤15 ml/s were selected at 72 sites in 11 European countries. The patients were entered into a 2-wk wash-out and a 4-wk placebo run-in period. A total of 955
patients were randomized (2:2:1) to silodosin 8 mg (n=381), tamsulosin 0.4 mg (n=384), or placebo (n=190) once daily for 12 wk.
Measurements: We calculated the change from baseline in IPSS total score (primary), storage and voiding subscores, quality of life (QoL) due to urinary symptoms, and Qmax. Responders were defined on the basis
of IPSS and Qmax by a decrease of ≥25% and an increase of ≥30% from baseline, respectively.
Results and limitations: The change from baseline in the IPSS total score with silodosin and tamsulosin was significantly superior to that with placebo ( p
reduced nocturia versus placebo (the change from baseline was -0.9, -0.8, and -0.7 for silodosin, tamsulosin, and placebo, respectively; p=0.013 for silodosin vs placebo). An increase in Qmax was observed in all groups. The adjusted mean change from baseline to end point was 3.77 ml/s for silodosin, 3.53 ml/s for tamsulosin, and 2.93 ml/s for placebo, but the change for silodosin and tamsulosin was not statistically significant versus placebo because of a particularly high placebo response (silodosin vs placebo: p=0.089; tamsulosin vs placebo: p=0.221). At end point, the percentage of responders by Qmax was 46.6%, 46.5%, and 40.5% in the silodosin, tamsulosin, and placebo treatment groups, respectively. This difference was not statistically significant (p=0.155 silodosin vs placebo and p=0.141 tamsulosin vs placebo).
Active treatments were well tolerated, and discontinuation rates due to adverse events were low in all groups (2.1%, 1.0%, and 1.6% with silodosin, tamsulosin, and placebo, respectively). The most frequent adverse event with silodosin was a reduced or absent ejaculation during orgasm (14%), a reversible effect as a consequence of the potent and selective a1A-adrenoreceptor antagonism of the drug. The incidence was
higher than that observed with tamsulosin (2%); however, only 1.3% of silodosin-treated patients discontinued treatment due to this adverse event.
Conclusions: Silodosin is an effective and well-tolerated treatment for the relief of both voiding and storage symptoms in patients with lower urinary tract symptoms suggestive of bladder outlet obstruction thought
to be associated with benign prostatic hyperplasia. Its overall efficacy is not inferior to tamsulosin. Only silodosin showed a significant effect on nocturia over placebo.
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