Helicobacter pylori Eradication in the Era of Rising Antibiotic Resistance: A Randomized Controlled Comparison of Clarithromycin- and Levofloxacin-Based Triple Therapy with or without Lactoferrin.

Background: Helicobacter pylori infection affects nearly half of the global population and is a major cause of peptic ulcer disease and gastric cancer. Increasing antibiotic resistance, particularly to clarithromycin, has reduced the efficacy of standard triple therapy, necessitating evaluation of alternative regimens and adjunctive therapies. Objectives: To compare the eradication rates and safety of clarithromycin- and levofloxacin-based triple therapy, with and without adjunctive lactoferrin. Methods: In this randomized, open-label, 2 × 2 factorial trial, 160 adult patients with confirmed H. pylori infection were allocated equally into four groups: clarithromycin-based triple therapy, levofloxacin-based triple therapy, and each regimen combined with lactoferrin. Treatments were administered for 14 days. Eradication was assessed using stool antigen testing four weeks after therapy. Analysis was performed according to the intention-to-treat principle. Results: Eradication rates were 72.5% in both the clarithromycin and levofloxacin groups, compared with 90.0% and 97.5% in the corresponding lactoferrin-supplemented groups, respectively (p = 0.003). Lactoferrin significantly improved eradication rates (72.5% vs. 93.8%, p < 0.001). No significant difference was observed between antibiotic regimens alone (p = 0.673). Adverse events were mild and comparable across groups. Conclusion: Adjunctive lactoferrin significantly enhances H. pylori eradication rates when combined with standard triple therapy, regardless of antibiotic backbone. The evidence proves that lactoferrin should function as an effective adjunct in eradication regimens, particularly in settings of increasing antibiotic resistance.