Comparison between optimized bismuth quadruple therapy and standard clarithromycin-based triple therapy for first-line Helicobacter pylori eradication: a double-blind randomized controlled trial.

Background: Helicobacter pylori eradication reduces the risk of peptic ulcer disease and gastric cancer. In Chile, the effectiveness of standard triple therapy has dropped below 80%. We compared optimized bismuth quadruple therapy: esomeprazole 40 mg three times a day, amoxicillin 1 gr three times a day, metronidazole 500 mg three times a day, and bismuth subsalicylate 369 mg three times a day for 14 days, and standard triple therapy omeprazole 20 mg twice a day, amoxicillin 1 gr twice a day, and clarithromycin 500 mg twice a day for 14 days in a Chilean population. Methods: Randomized double-blind clinical trial. 127 treatment-naïve individuals with confirmed active H. pylori were recruited. The primary outcome was successful H. pylori eradication, at least 4 weeks post-treatment. We assessed H. pylori resistance to clarithromycin and participants' CYP2C19 genotype/phenotype. We compared eradication success between the groups using intention-to-treat and per-protocol analyses. The trial adhered to CONSORT guidelines. NTC-Number: NCT05664685 (trial completed). Findings: 127 participants were recruited and randomized (64 standard triple therapy, 63 optimized bismuth quadruple therapy). Men were 44% (56/127), and the mean age was 48 (standard deviation: 14.2) in the sample. Baseline characteristics between the two groups were similar. In intention-to-treat analysis, optimized bismuth quadruple therapy had a significantly higher eradication rate versus standard triple therapy: 95% (60/63) [95% CI 86%-99%] vs. 81% (52/64) [70%-89%], p = 0.033. Adverse events were comparable: optimized bismuth quadruple therapy 67% (42/63) [54%-77%] vs. standard triple therapy 66% (42/64) [53%-76%], p = 1.00. There was no difference in baseline clarithromycin resistance or CYP2C19 polymorphisms. Interpretation: Optimized bismuth quadruple therapy eradication is higher than standard triple therapy in treatment-naïve individuals with active H. pylori, without difference in adverse events or adherence. Optimized bismuth quadruple therapy is a reliable and safe empiric eradication therapy, especially in areas with high clarithromycin resistance. Funding: FONDECYT (1230504 AR); ANID-FONDAP (152220002 AR); Horizon 2020 program of European Union (825832 AR); ANID-FONDAP (15130011).