The Small-Intestinal-Submucosa (SIS) as a Suburethral Sling for Correction of Stress Urinary Incontinence in Females: Preliminary Experience

ABSTRACT

Introduction and Objectives: The objectives of this clinical study were to demonstrate non-inferiority of oral trospium chloride (TC) in comparison to oxybutynin (OXY), and to evaluate efficacy, safety, and quality of life parameters when using either substance in the treatment of patients with urge urinary incontinence.

Methods: This study was a multicentre study carried out in Germany. It was randomised, double-blind, controlled, and involved parallel groups. Patients (age ≥ 18) with urinary frequency (≥ 8 micturitions daily) and urge incontinence (≥ 5 episodes per week) were enrolled. Both were documented in a 7-day diary during the screening phase. The patients also recorded numbers of micturitions and incontinence episodes, degree of urgency, and (on 2 successive days) the voided volumes during weeks 4 and 12 of the trial. The primary efficacy parameter was the absolute reduction in urge incontinence episodes/week comparing baseline values with those of last treatment week (week 12). Secondary efficacy parameters were the absolute reduction of micturitions/24 hours, subjective treatment outcome (visual analogue scale, VAS), changes in quality of life (King's Health Questionnaire, KHQ), intensity of urgency, changes in mean micturition volume, and the intensity of "dry mouth" (scale: none, mild, moderate, severe). A supplementary examination concerned the changes in health-related quality of life measured by a generic instrument (Short Form (SF)-36 questionnaire). Given a non-clinical relevant difference of 3.5 or less incontinence episodes/week, a two group one-sided ttest (α=0.025) has 90% power to reject the null hypothesis. As a non-inferiority hypothesis is tested by the per protocol (PP) set, 1410 patients were planned to be randomised. In fact, 1659 patients were randomised, of whom 829 received 45 mg TC/day and 830 received 7.5 mg OXY/day until the intermediate visit (week 4). The daily dose could be maintained or doubled after 4 weeks of treatment. In the group with an adjusted dose, a single reduction to the start dose was allowed. The trial was funded by Dr. R. Pfleger GmbH, Bamberg, Germany. The study was approved by the Ethics Committee of the Bayerische Landesärztekammer, Munich, Germany and was performed in compliance with the EC-GCP and Declaration of Helsinki. Informed consent was obtained from the patients.

Results: TC was comparable to OXY in terms of the reduction in the number of urge incontinence episodes/week after 12 weeks of treatment. In the PP population the median change was -11.00 (full analysis set (FAS): -10.42) for TC and -11.00 (FAS: -10.00) for OXY. The reduction of mean number of micturitions/day, mean intensity of urgency, and increase in mean micturition volume were comparable in both treatment groups (FAS) after 12 weeks of treatment. The problems due to incontinence (VAS) and quality of life (median change in KHQ domain total score: -16.17 for TC and -15.76 for OXY) were improved to a similar extent in both treatment groups (FAS) at the end of treatment. Overall, the KHQ domains revealed only minimal differences between treatments. With respect to the median changes, a clinically relevant improvement was found for 7 out of 10 KHQ domains. The greatest improvements (median changes > 30) were detected in the KHQ domains incontinence impact and role limitations. Regarding the secondary parameter "intensity of dry mouth", the worsening of "dry mouth" intensity was significantly lower (p < 0.0001) in the TC group than in the OXY group (worsening for TC: 51.2%; OXY: 64.4%, FAS) at the final examination. Concerning the supplementary examination, the changes inall 9 SF-36 scores were similar in both treatment groups, indicating only minimal differences between TC and OXY.

Conclusion: Overall, TC was shown to be as efficacious and as safe as OXY in the treatment of urge incontinence but showed an advantage in tolerance in particular with regard to the most common antimuscarinic adverse drug reaction "dry mouth".

KEYWORDS: Efficacy, oxybutynin, quality of life, tolerability, trospium chloride, urge urinary incontinence

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