Trospium chloride and oxybutynin hydrochloride in a german study of adults with urinary urge incontinence: Results of a 12-week, multicenter, randomized, double-blind, parallel-group, flexible-dose noninferiority trial

Abstract Objectives: The aims of this study were to determine whether oral trospium chloride is noninferior to oxy-butynin for urinary urge incontinence and to evaluate its efficacy, tolerability, and health-related quality of life parameters. Methods: In this randomized, double-blind, active-controlled, parallel-group, multicenter, Phase IIIb trial conducted in Germany, male and female outpatients aged ≥18 years with documented urinary frequency (≥8 micturitions/24 hours) plus urge incontinence (≥5 episodes/week) were randomized to receive oral treatment with trospium chloride 15 mg TID or oxybutynin hydrochloride 2.5 mg TID for 12 weeks. Daily doses could be adjusted upward after 4 weeks, to 90 mg of trospium (30 mg TID) and 15 mg of oxybutynin (5 mg TID), respectively, if needed. The absolute reduction in weekly episodes of urinary urge incontinence was evaluated as the primary efficacy variable. Secondary variables included the absolute reduction of micturitions per 24 hours, intensity of urgency, and mean voided volume. Qualitative symptom changes were recorded from the patients' entries in their micturition diaries at baseline, at week 4, and at week 12 of treatment. Subjective treatment outcome was assessed by patient ratings on a visual analog scale (VAS), the King's Health Questionnaire (KHQ), and the 36-Item Medical Outcomes Study Short-Form General Health Survey (SF-36); intensity of dry mouth was also recorded on a scale. Adverse events (AEs) were assessed. Results: Of the 1658 patients treated, 828 patients (49.9%) received trospium 45 mg/d and 830 patients (50.1%) received oxybutynin 7.5 mg/d. After 4 weeks, daily doses were doubled in 29.2% (242/828) of patients in the trospium chloride group, and in 23.3% (193/830) of patients in the oxybutynin group, until the end of treatment. No clinically relevant differences in demographic characteristics were observed between the treatment groups. Trospium was noninferior to oxybutynin hydrochloride in terms of the reduction in the number of weekly urge incontinence episodes after 4 and 12 weeks of treatment. In the per-protocol population, the median change after 12 weeks was −11.0 in both groups. In the full analysis set, the median change was −10.42 with trospium chloride and −10.00 with oxybutynin ( P < 0.001 for the noninferiority hypothesis, for both the per-protocol and the full analysis set calculations). There was also no indication of a difference between groups concerning the observed reduc