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

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

Acknowledgments

This work was supported by Repha GmbH.

Disclosure

Repha GmbH has not been involved in trial design, data collection, analysis, or decision to publish this manuscript. The authors report no conflicts of interest in this work.