Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial

Urol Int. 2018;101(3):327-336. doi: 10.1159/000493368. Epub 2018 Sep 19.


Introduction: This randomized, controlled, Phase III non-inferiority clinical trial aimed to determine whether herbal therapy with Canephron® N (BNO 1045) is non-inferior to fosfomycin trometamol (FT) in treating acute lower uncomplicated urinary tract infections (uUTIs).

Materials and methods: Women aged 18-70 years with typical symptoms of newly diagnosed acute lower uUTIs were randomized to BNO 1045 (n = 325) or FT (n = 334), with corresponding matched placebo. The primary endpoint was the proportion of patients who received additional antibiotics (ABs) to treat uUTIs between Days 1 and 38 ±3.

Results: Between Days 1 and 38, 238 (83.5%) patients in the BNO 1045 group and 272 (89.8%) patients in the FT group received no additional ABs. At a 15% non-inferiority margin, BNO 1045 was non-inferior to FT in treating uUTIs (non-AB rate difference: -6.26%; 95% CI -11.99 to -0.53%; 2-sided p = 0.0014). Adverse event rates were similar between groups, with higher rates of gastrointestinal disorders in the FT group and pyelonephritis in the BNO 1045 group. During the trial, no patient died or discontinued due to a treatment-related adverse event.

Conclusions: BNO 1045 has the potential to reduce outpatient use of ABs for uUTIs and thus may have a significant impact on antimicrobial stewardship strategies.

Trial registration: NCT02639520, EudraCT number 2013-004529-99.

Keywords: Antibiotics; Herbal treatment; Symptomatic treatment; Urinary tract infection.

Publication types

  • Clinical Trial, Phase III
  • Equivalence Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents / therapeutic use
  • Double-Blind Method
  • Europe
  • Female
  • Fosfomycin / therapeutic use*
  • Humans
  • International Cooperation
  • Middle Aged
  • Outpatients
  • Phytotherapy
  • Plant Extracts / therapeutic use
  • Plant Preparations / therapeutic use*
  • Sample Size
  • Tromethamine / therapeutic use*
  • Urinary Tract Infections / drug therapy*
  • Young Adult


  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Plant Extracts
  • Plant Preparations
  • canephron N
  • Tromethamine
  • Fosfomycin

Associated data