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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.
Eur Urol. 2011 Mar; 59(3):342-52.EU

Abstract

BACKGROUND

Silodosin is a new selective therapy with a high pharmacologic selectivity for the α(1A)-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 double-blind, 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 (Q(max)) >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 Q(max). Responders were defined on the basis of IPSS and Q(max) 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<0.001): difference active placebo of -2.3 (95% confidence interval [CI], -3.2, -1.4) with silodosin and -2.0 (95% CI,-2.9, -1.1) with tamsulosin. Responder rates according to total IPSS were significantly higher (p<0.001) with silodosin (66.8%) and tamsulosin (65.4%) than with placebo (50.8%). Active treatments were also superior to placebo in the IPSS storage and voiding subscore analyses, as well as in QoL due to urinary symptoms. Of note, only silodosin significantly 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 Q(max) 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 Q(max) was 46.6%, 46.5%, and 40.5% in the silodosin, tamsulosin, and placebo treatment groups, respectively. This difference was not statistically significantly (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 α(1A)-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.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier NCT00359905.

Authors+Show Affiliations

Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK. c.r.chapple@shef.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21109344

Citation

Chapple, Christopher R., et al. "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." European Urology, vol. 59, no. 3, 2011, pp. 342-52.
Chapple CR, Montorsi F, Tammela TL, et al. 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. Eur Urol. 2011;59(3):342-52.
Chapple, C. R., Montorsi, F., Tammela, T. L., Wirth, M., Koldewijn, E., & Fernández Fernández, E. (2011). 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. European Urology, 59(3), 342-52. https://doi.org/10.1016/j.eururo.2010.10.046
Chapple CR, et al. 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. Eur Urol. 2011;59(3):342-52. PubMed PMID: 21109344.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Chapple,Christopher R, AU - Montorsi,Francesco, AU - Tammela,Teuvo L J, AU - Wirth,Manfred, AU - Koldewijn,Evert, AU - Fernández Fernández,Eldiberto, AU - ,, Y1 - 2010/11/10/ PY - 2010/07/30/received PY - 2010/10/31/accepted PY - 2010/11/27/entrez PY - 2010/11/27/pubmed PY - 2011/7/28/medline SP - 342 EP - 52 JF - European urology JO - Eur Urol VL - 59 IS - 3 N2 - BACKGROUND: Silodosin is a new selective therapy with a high pharmacologic selectivity for the α(1A)-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 double-blind, 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 (Q(max)) >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 Q(max). Responders were defined on the basis of IPSS and Q(max) 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<0.001): difference active placebo of -2.3 (95% confidence interval [CI], -3.2, -1.4) with silodosin and -2.0 (95% CI,-2.9, -1.1) with tamsulosin. Responder rates according to total IPSS were significantly higher (p<0.001) with silodosin (66.8%) and tamsulosin (65.4%) than with placebo (50.8%). Active treatments were also superior to placebo in the IPSS storage and voiding subscore analyses, as well as in QoL due to urinary symptoms. Of note, only silodosin significantly 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 Q(max) 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 Q(max) was 46.6%, 46.5%, and 40.5% in the silodosin, tamsulosin, and placebo treatment groups, respectively. This difference was not statistically significantly (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 α(1A)-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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00359905. SN - 1873-7560 UR - https://www.unboundmedicine.com/medline/citation/21109344/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0302-2838(10)01058-4 DB - PRIME DP - Unbound Medicine ER -