Research and Reports in Urology (Mar 2017)
Results of a randomized, prospective, double-dummy, double-blind trial to compare efficacy and safety of a herbal combination containing Tropaeoli majoris herba and Armoraciae rusticanae radix with co-trimoxazole in patients with acute and uncomplicated cystitis
Abstract
Rainer Stange,1 Berthold Schneider,2 Uwe Albrecht,3 Valentina Mueller,3 Joerg Schnitker,4 Andreas Michalsen1 1Internal and Complementary Medicine, Immanuel Krankenhaus Berlin-Wannsee, Berlin, 2Institute for Biostatistics, Medical University, 3Mediconomics GmbH, Hannover, 4Institute for Applied Statistics, Bielefeld, Germany Objectives: To demonstrate non-inferiority of an herbal combination (horseradish root and nasturtium herb) to an antibiotic (co-trimoxazole) in acute uncomplicated cystitis. Design: Randomized, prospective, double-blind, double-dummy, multicenter, phase III clinical study, using block randomization of 4 blocks (size 2). Setting: Twenty-six centers in Germany, from May 2011 to June 2013. Participants: Adult patients (median age, 38.5 years; 90% female) with acute uncomplicated cystitis confirmed via urinalysis and bacterial counts. Interventions: Patients received the herbal combination (five tablets, four times per day) or the antibiotic (two tablets daily) for a period of 7 or 3 days, respectively, followed by a 21-days without drug treatment. Placebos ensured blinding. Primary and secondary outcome measures: The primary endpoint was the percentage of responders, expressed as reduction of germ count from >105 to <103 CFU/mL of pathogens between visit 1 (day 0) and 3 (day 15). Secondary endpoints included change of symptom scores, duration of symptoms, efficacy assessments, relapse frequency, and safety. A sample size of 178 patients per group was estimated. Results: Of the 96 randomized patients (intent-to-treat; 45 in the phytotherapy group, 51 in the antibiotic group), 51 were considered per-protocol patients (22 in the phytotherapy group, 29 in the antibiotic group). Responder rates were 10/22 (45.5%) for the phytotherapy group and 15/29 (51.1%) for the antibiotic group (group difference: –6.27% [95% CI: –33.90%–21.3%]). The study was terminated prematurely due to slow recruitment rates. Non-inferiority could not be assumed by predefined criteria. During the follow-up period, one relapse occurred in each group. Both treatments were well tolerated. Conclusion: This clinical trial indicates comparable efficacy of the herbal combination and antibiotic, although non-inferiority was not proved. However, the results and lessons learned are important for the planning of future trials. Issues that led to the premature trial discontinuation were considered. Keywords: urinary tract infection, herbal medicinal product, cystitis, horseradish, nasturtium herb, co-trimoxazole, randomized clinical trial
