OBJECTIVES: To determine the clinical effectiveness and safety of alpha(1)-blockade therapy versus placebo in the treatment of men with moderate to severe symptoms of prostatism in a community-based population under usual care conditions. METHODS: The Hytrin Community Assessment Trial is a prospective, placebo-controlled, randomized, double-blinded, 1-year clinical trial, conducted at 15 academic medical centers (regional sites) and 141 private urology practices (satellite sites). A total of 2084 men at least 55 years old with moderate to severe symptoms of benign prostatic hyperplasia (BPH) as determined by an American Urological Association (AUA) Symptom Score (AUA-SS) of 13 or more points and a bother score (AUA-BS) of 8 or more were enrolled. Randomized patients at regional sites were required to have a peak urinary flow rate less that 15 mL/s with voided volume of at least 150 mL. Treatment with terazosin was initiated with 1 mg daily for 3 days, followed by 2 mg daily for 25 days. Thereafter, patients were titrated stepwise to 5 or 10 mg if they failed to achieve a 35% or greater improvement in the AUA-SS. Primary outcome measures were AUA-SS, AUA-BS, BPH Impact Index (BII), disease-specific quality of life (QQL) score, and treatment failure as defined as discontinuation due to persistent or worsening symptoms or need for surgical intervention for BPH. Secondary outcome measures were peak urinary flow rate and postvoid residual urine volume. RESULTS: AUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001). CONCLUSIONS:Terazosin given once daily in a dose ranging from 2 to 10 mg in community-based urology practices under conditions simulating usual care is effective in reducing the symptoms, perception of bother, and the impairment of QQL due to urinary symptoms in men with moderate to severe symptoms of prostatism. This effect is superior to placebo and maintained over 12 months of follow-up. Clinical research outcome studies in BPH can be conducted in community-based practices, thus simulating as closely as possible "usual care" conditions.
RCT Entities:
OBJECTIVES: To determine the clinical effectiveness and safety of alpha(1)-blockade therapy versus placebo in the treatment of men with moderate to severe symptoms of prostatism in a community-based population under usual care conditions. METHODS: The Hytrin Community Assessment Trial is a prospective, placebo-controlled, randomized, double-blinded, 1-year clinical trial, conducted at 15 academic medical centers (regional sites) and 141 private urology practices (satellite sites). A total of 2084 men at least 55 years old with moderate to severe symptoms of benign prostatic hyperplasia (BPH) as determined by an American Urological Association (AUA) Symptom Score (AUA-SS) of 13 or more points and a bother score (AUA-BS) of 8 or more were enrolled. Randomized patients at regional sites were required to have a peak urinary flow rate less that 15 mL/s with voided volume of at least 150 mL. Treatment with terazosin was initiated with 1 mg daily for 3 days, followed by 2 mg daily for 25 days. Thereafter, patients were titrated stepwise to 5 or 10 mg if they failed to achieve a 35% or greater improvement in the AUA-SS. Primary outcome measures were AUA-SS, AUA-BS, BPH Impact Index (BII), disease-specific quality of life (QQL) score, and treatment failure as defined as discontinuation due to persistent or worsening symptoms or need for surgical intervention for BPH. Secondary outcome measures were peak urinary flow rate and postvoid residual urine volume. RESULTS: AUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001). CONCLUSIONS:Terazosin given once daily in a dose ranging from 2 to 10 mg in community-based urology practices under conditions simulating usual care is effective in reducing the symptoms, perception of bother, and the impairment of QQL due to urinary symptoms in men with moderate to severe symptoms of prostatism. This effect is superior to placebo and maintained over 12 months of follow-up. Clinical research outcome studies in BPH can be conducted in community-based practices, thus simulating as closely as possible "usual care" conditions.
Authors: R F Schäfers; B Fokuhl; A Wasmuth; H Schumacher; K Taguchi; C de Mey; T Philipp; M C Michel Journal: Br J Clin Pharmacol Date: 1999-01 Impact factor: 4.335