STUDY SUMMARY: Silodosin Therapy for Lower Urinary Tract Symptoms in Men with Suspected Benign Prostatic Hyperplasia: Results of an International, Randomised, Double-Blind, Placebo- and Active-Controlled Clinical Trial Performed in Europe.
Chapple CR, Montorsi F, Tammela TL, et al. Eur Urol. 2011; 59(3): 342-521
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STUDY OBJECTIVES
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To test silodosin’s superiority to placebo and non-inferiority to tamsulosin for the relief of LUTS associated with BPH and suggestive of BOO and discuss findings in the context of a comprehensive literature review of silodosin.
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STUDY DESIGN
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A multicentre double-blind, placebo- and active-controlled parallel-group study including men ≥50 years of age with LUTS (defined by a stable IPSS total score ≥13 points), BOO (defined by a Qmax between 4 and 15 mL/s, with a minimum voided volume of ≥125 mL) and evidence of satisfactory compliance with study medication following a placebo run-in period.
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PRIMARY ENDPOINTS:
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- Superiority of silodosin vs. placebo (ITT population; silodosin, n = 371; placebo, n = 185)
- Non-inferiority of silodosin vs. tamsulosin (PP population; silodosin, n = 346; tamsulosin, n = 347)
Measured by a change from baseline in the total score (questions 1–7) of the IPSS questionnaire for the relief of LUTS associated with BPH and suggestive of BOO.
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SECONDARY ENDPOINTS:
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- Improvement in storage and voiding symptoms subscores
- QoL due to urinary symptoms (question 8 of the IPSS)
- Qmax, and percentage of treatment responders by IPSS (decrease from baseline ≥25%)
- Qmax (increase from baseline ≥30%)
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POST HOC ANALYSIS:
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- Conducted in the subgroup of patients (n = 764) with nocturia at baseline (defined as at least two voids per night), as assessed by question 7 of the IPSS.
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RESULTS
PRIMARY ENDPOINT: Change from baseline in IPSS total score
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Silodosin demonstrated superiority vs. placebo with statistically significant differences in reduction from baseline at Week 12 (-7.0 vs. -4.7, P < 0.001, ITT population).
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CHANGES IN IPSS TOTAL SCORE FROM BASELINE
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For the analysis of the primary efficacy variable, superiority of silodosin vs. placebo was tested first in the intent-to-treat (ITT) population. Thereafter, the non-inferiority of silodosin vs. tamsulosin was tested in the per-protocol (PP) population.
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RATE OF RESPONSE TO IPSS
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POST HOC ANALYSIS OF NOCTURIA
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7 out of 10 patients responded* to treatment with silodosin or tamsulosin by end of study (silodosin, 66.8%; tamsulosin, 65.4% vs. placebo, 50.8%).
*Defined by percentage of responders (who experienced IPSS decrease from baseline ≥25%)
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In the subgroup of patients with nocturia at baseline (n = 764), only silodosin, significantly reduced nocturia vs. placebo, assessed by question 7 of the IPSS.
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SAFETY
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- The percentage of subjects with treatment related adverse events was similar between silodosin (34.9%) and tamsulosin (28.9%), P = 0.0749 with silodosin higher than placebo (24.2%, P = 0.0094)
- The most frequently reported treatment-related adverse event (>2%) was reduced or absent ejaculation during orgasm (silodosin, 14.2%, 54/381 patients; tamsulosin, 2.1%, 8/384 patients)
- Percentage of study discontinuation due to a TEAE was small in the treatment groups (silodosin, 2.1%; tamsulosin, 1.0%; placebo, 1.6%)
- Silodosin did not demonstrate any changes in blood pressure or heart rate vs. placebo
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CLINICAL IMPLICATIONS
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"A major advantage of this drug is its lack of cardiovascular side effects"
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"It may be particularly useful in more elderly patients where there is the potential for drug-drug interactions and where potential cardiovascular side effects need to be minimised."
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"Studies conducted recently have suggested silodosin, as a consequence of its high subtype selectivity, is less likely than tamsulosin to have significant cardiovascular side effects either when used alone or in combination with other agents, which may affect blood pressure. This is particularly important and relevant in more elderly patients."
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