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

Abstract

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.

UTI − quo vadis? New alternatives to treat uncomplicated urinary tract infections

“…In the four larger studies [4,14,16,17] in the nonantibiotic treatment arm 5-7 cases per study experienced pyelonephritis as comparted to 0-1 case treated with antibiotics.…”

“…But in all three studies there was a marked reduction of antibiotic usage. However, the highest reduction in antibiotic use was seen for the multimodal phytotherapy combination of the three plant combination (BNO 1045), with symptomatic relief being comparable in the phytotherapy and antibiotic groups [4].…”

“…A recommendable approach to this therapeutic regimen could be the use of a phytotherapeutic product supported by an adequate level of evidence, e.g. a combination of lovage root, centaury herb and rosemary leaves (BNO 1045) [4].…”

“…Recent data now also show that non-antimicrobial treatment may be an appealing therapeutic option and provides an alternative to what is usually first-line antibiotic therapy [4]. But why should we replace antibiotic therapy anyway?…”

Xyloglucan + Gelose Combination versus Placebo as Adjuvant Therapy to First-Line Antimicrobials for Uncomplicated Urinary Tract Infection in Adults

“…The herbal product, BNO 1045, which is a combination of centaury powder, lovage root powder, and rosemary leaf powder, was recently shown to be non-inferior to fosfamycin for treating newly diagnosed acute uncomplicated UTI in women [10]. Mucosal barrier protectors such as xyloglucan (hemicellulose) and gelatin offer protection of the intestinal mucosa against pathogens [11,12].…”