A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence.

OBJECTIVE: To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a randomized, double-blind placebo-controlled clinical trial. PATIENTS AND METHODS: In all, 366 patients (149 on propiverine, 145 oxybutynin and 72 placebo, ratio 2:2:1) with urgency and urge incontinence were recruited in 32 study centres. Propiverine (group 1, 15 mg three times daily), oxybutynin (group 2, 5 mg twice daily) or placebo (group 3) were administered for 4 weeks, using the double-dummy technique. The dosages were selected specifically to compare the tolerability profile of propiverine with the commonly used therapeutic dosage of oxybutynin. Tolerability was assessed by directly questioning the patients about adverse events at four visits (V-1 before and V0 after a 1-week 'washout' period, V1 after 1 week and V4 after 4 weeks of treatment) during a 5-week surveillance period, and by tolerability ratings of the physicians. Efficacy was assessed using urodynamics at V0 and V4, evaluating the cystometric bladder capacity at maximal and first desire to void, and postvoid residual urine, according to the criteria of the International Continence Society. Additionally, a voiding protocol, overall assessment of clinical symptomatology and efficacy ratings by the physicians were documented.
RESULTS: A remarkably high percentage of adverse events was reported in the washout period (VO: 13%, 16% and 18% in groups 1-3, respectively). At V4, the clinically most relevant symptom (dry mouth) occurred in 53% of patients in group 1, in 67% of group 2 and in 28% of group 3. Furthermore, dry mouth was less severe in group 1 than group 2. In contrast to groups 2 and 3, only patients in group 1 showed increasing tolerability during the treatment (from V1 to V4). These tolerability results were further supported by the overall tolerability assessment ('very good' or 'good' tolerability in 67% of group 1, in 59% of group 2 and in 83% of group 3). The urodynamic assessment of efficacy (comparing V0 and V4) showed a statistically significant increase in the mean (sd) maximal cystometric bladder capacity in group 1, being 222 (77) mL at V0 and 311 (125) mL at V4, an increase of 89 (108) mL, and in group 2, at 226 (75) mL and 322 (123) mL, an increase of 96 (106) mL, compared with group 3, at 211 (77) mL and 263 (93) mL, an increase of only 52 (92) mL. The cystometric bladder capacity at first desire to void also increased in group 1 (93 to 160 mL) and group 2 (89 to 160 mL), whereas in group 3 there were only minor changes (93 to 120 mL). Changes in the residual urine volume within and between the treatment groups were minimal and clinically irrelevant. The overall assessment of efficacy showed significant differences between the drugs when compared with placebo.
CONCLUSION: Propiverine is a safe and effective drug in the treatment of urgency and urge incontinence; it is as effective as oxybutynin, but the incidence of dry mouth and its severity is less with propiverine than with oxybutynin. The availability of alternative pharmacotherapeutics such as propiverine should reduce the therapeutic failure rate and improves the success rate in the treatment of patients suffering from urgency and urge incontinence.

RCT Entities:   Population Interventions Outcomes