Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size: A Double-blind, Placebo-controlled, Randomized Clinical Trial

Abstract

Background:

The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release (ER) with or without tamsulosin in patients with benign prostate hyperplasia (BPH) and larger prostate size.

Methods:

Totally, 152 patients (age ≥50 years) with BPH, International Prostate Symptom Score (IPSS) ≥12, quality-of-life (QoL) score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups ( n = 38 in each) to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS (total, storage, and voiding subscales), QoL, maximum urinary flow rate ( Q _max), and postvoid residual volume (PVR) were collected at baseline, and at weeks 4, 12, and 24.

Results:

Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS (−7.15, −12.20, and −14.66 vs. −3.51, −5.78, and −7.23), storage IPSS (−3.56, −5.63, and −6.66 vs. −1.52, −1.21, and −2.43), voiding IPSS (−2.88, −5.10, and −6.48 vs. −1.52, −3.03, and −2.97), QoL (−1.21, −2.40, and −3.21 vs. −0.39, −1.41, and −1.60), Q _max (2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s), and PVR (−17.88, −26.97, and −27.89 ml vs. −12.03, −11.16, and −16.73 ml) at weeks 4, 12, and 24, respectively; the differences were all statistically significant ( P < 0.05). Adverse events (AEs) were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS (−4.61, −6.79, and −5.70), voiding IPSS (−0.64, −1.83, and −1.45), QoL (−0.69, −1.21, and −1.41), or Q _max (−0.79, 2.83, and 1.11 ml/s), compared with placebo (all P > 0.05). However, a gradual increase in PVR (10.03, 10.41, and 12.89 ml) and more urinary AEs suggestive of urinary retention (11/38 vs. 4/38) were observed.

Conclusion:

Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume.

Trial Registration:

www.chictr.org.cn, ChiCTR-TRC-09000596; http://www.chictr.org.cn/showproj.aspx?proj=8939.