Clinical Studies with Spasmo-lyt
Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial
Brit.J.Urol. International 2000; 85: 659-664
L.Cardazzo(1), C.R. Chapple(2), P. Toozs-Hobson(1), M.Grosse-Freese(3), M.Bulitta(3), W.Lehmacher(4), W.Strösser(5), B.Ballering-Brühl(3), and M.Schäfer(3)
(1) Kings College Hospital, London
(2) Royal Hallamshire Hospital
(3) Research and Development, Medical Department, Madaus AG, Cologne, Germany
(4) Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Germany
(5) CRP-Consulting, Bergisch-Gladbach, Germany
Keywords: adaptive design, detrusor instability, anticholinergics, trospium chloride, CAS 10405-02-4, urodynamic measurement
Abstract: Objectives: To assess the efficacy and safety of trospium chloride (TCI, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo.
Patients and methods: In all, 208 patients were allocated at random to either TCI or placebo in a double-blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy.
Results: Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 ml, mean 37.3 ml, one-sided P=0.0054) and urinary volume at first unstable contraction (median treatment effect 45.0 ml, mean 63.3 ml, one-sided P=0.0015). The patients' assessment of efficacy showed significantly greater clinical improvement in the TCI group than in the placebo group (two-sided P=0.0047). Furthermore, TCI was well tolerated, with similar frequencies af adverse events reported in both groups (68% in the TCI and 62% in the placebo group).
Conclusion: Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.
Trospium chloride (Spasmo-lyt®) in patients with motor urge syndrome (detrusor instability): a double-blind, randomised, multicentre, placebo-controlled study
Journal of Clinical Research 1998; 1: 439-451
S Alloussi(1), K-U Laval(2), R Eckert(1), B Ballering-Brühl(3), M Grosse-Freese(3), M Bulitta(3), M Schäfer(3)
(1)Department of Urology, University Hospital, Homburg, Germany
(2) Consultant Urologist, Münsterstrasse 353, Düsseldorf, Germany
(3) Research and Development, Medical Department, Madaus AG, Cologne, Germany
Keywords: motor urge syndrome, detrusor instability, anticholinergics, trospium chloride
Abstract: Trospium chloride* (TCI; code MP94) is a parasympatholytic with antispasmodic and ganglion blocking properties. The aim of this study was to evaluate the efficacy and tolerability of TCI in the treatment of motor urge syndrome. TCI (20 mg b.d.) given for three weeks was compared with placebo in a total of 309 patients (TCI: n = 210; placebo n = 99; allocation ratio 2:1). Primary efficacy variables were urodynamically measured maximum cystometric bladder capacity (BC) and the volume at first unstable contraction (VC). In the per-protocol analysis BC increased markedly more in the patients receiving TCI (n = 99) than in those receiving placebo (n = 48); treatment effect: + 73.9 ml, 95% CI 38.4 to 109.0 ml, p = 0.0001. The increase in VC was more pronounced in the TCI group compared to the placebo group (treatment effect: +55.0 ml, 95% CI 15.4 to 94.6 ml, p = 0.0027). Intention-to-treat analysis yielded almost identical results. In patients with motor urge syndrome, trospium chloride increased maximum bladder capacity and volume at first unstable contraction and was well tolerated (TCI: 19.0%, placebo: 15.2% of the patients reported adverse events).
*Spasmolyt®, Uroplex® and Spasmo-Urgenin® Nco are registered trademarks of Madaus AG, Cologne, Germany
Trospium chloride in patients with detrusor overactivity - Meta-analysis of placebo-controlled, randomized, double-blind, multi-center clinical trials in the efficacy and safety of 20 mg trospium chloride twice daily
International Journal of Clinical Pharmacology and Therapeutics 2002; 40(7): 295-303
G. Fröhlich(1), M. Bulitta(2), W. Strösser(3)
(1)Urologist, Toscolano Maderno, Italy,
(2)Biometrican, CRMB GmbH, Rheinbach,
(3)Medical Consultant, Bergisch Gladbach, Germany
Keywords: Keywords: detrusor overactivity, trospium chloride, urodynamic measurement, meta-analysis, clinical trials
Abstract: Objectives: Primary objective of this meta-analysis was to produce a systematic and quantitative review of two independent clinical trials of 20 mg trospium chloride (TCI) twice daily (b.i.d.) in patients with detrusor overactivity [Alloussi et al. 1998, Cardozo et al. 2000]. Patients and methods: In two placebo-controlled, double-blind, multi-center studies, the effect of TCI on detrusor function was evaluated using urodynamic measurements. All 517 patients were randomized to receive TCI or placebo for 3 weeks. Urodynamic variables were measured at the beginning and at the end of the treatment. Safety was evaluated on the basis of adverse events (AEs), vital signs and laboratory tests. Results: TCI produced significant improvements in "maximum cystometric bladder capacity" (median treatment effect = 52 ml, 95% confidence interval 32-71 ml, p lt 0.0001) and "urinary volume at first unstable contraction" (median treatment effect = 48 ml, 95% confidence interval 28 to 68 ml, p = 0.0001). The patients' assessment of efficacy also showed significantly greater clinical improvement on the TCI group than in the placebo group (p lt 0.0001). The patients recordet a "cure" or a "marked improvement" more often in the TCI group than in the placebo group (47.9% and 19.7%, respectively). TCI was well tolerated, with similar frequencies of AEs reported in both groups (TCI: 35.7%, placebo group: 38.9%). Conclusions: Trospium chloride (20 mg twice daily) is an effective and safe medication for the treatment of detrusor overactivity.
Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability
World J Urol (2003) 20:392-399
M. Halaska(1), G. Ralph(2), A. Wiedemann(3), G. Primus(4), B. Ballering-Brühl(5), K. Höfner(6), U. Jonas(7)
(1)Gynaekologicka-porodnická Klinika, Unemocnice 2, 128008 Prague, Czech Reprublic
(2)Gynäkologische Abteilung, Landeskrankenhaus, Bruck a.d. Mur, Austria
(3)Urologische Abteilung, Marienhospital Gelsenkirchen, Germany
(4)Urologie, Universitätsklinikum Graz, Graz, Austria
(5)Madaus AG, Köln, Germany
(6)Urologische Klinik, Evangelisches Krankenhaus, Virchowstrasse 20, 46047 Oberhausen, Germany
(7)Urologische Klinik der Medizinischen Hochschule, Hannover, Germany
Keywords: Keywords: Anticholinergics, Trospium chloride (TCI), Oxybutynin (OXY), Detrusor Instability, Urodynamic measurement
Abstract: Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in patients with urge syndrome or urge incontinence. After randomisation in the ratio of 3:1, participants were treated continuously for 52 weeks with either trospium chloride (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks, patients were phyically exermined with measurments of blood pressure and pulse rate, were questioned about any adverse events, checked for compliance and underwent relevant laboratoy tests. As an additional safety measure, an ECG was made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning, and at 26 and 52 weeks to determine the maximal cystometric bladder capacity. Among others things, the frequencies of micturition, incontinence and number of urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52. The evaluation of vital parameters, laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics. Analysis of the micturition diary clearly indicated a reduction of the micturation frequency, incontinence frequency, and a reduction of the number of urgencies in both treatment groups. Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks (P = 0.001). Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs. Adverse events occured in 64.8% of the patients treated with trospium chloride and 76.7% of those treated with oxybutynin. The main symptom encountered in both treatment group was dryness of the mouth. For patients on trospium chloride, the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth, resulting in a considerably lower risk during treatment given with trospium chloride than with oxybutynin (0.045 and 0.021, respectively). An overall assessement for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability.