Empirical Rescue Eradication Therapy for Helicobacter pylori Infection in Second and Subsequent Treatment Lines: Experience From 500 Cases of the Brazilian Registry on H. pylori Management (Hp‐BrazilReg)

Background The effectiveness of anti ‐ H. pylori treatment diminishes with therapy failure, making regional performance understanding crucial. Objective To evaluate the effectiveness of empirical therapy in second‐line and subsequent treatments in Brazil. Methods A multicenter, prospective, noninterventional registry assessed H. pylori management outcomes by Brazilian gastroenterologists (Hp‐BrazilRe, Hp‐ WorldReg 's partner). Data were registered at e‐ CRF AEG ‐ ReCap from March 2022 to October 2024 and analyzed via modified intention‐to‐treat ( mITT ) methodology. Data were subject to quality review. Results 572 patients (mean age 52 years, 64% women) were included. The primary treatment indications were dyspepsia (64%) and gastroduodenal ulcer (9.2%). Among them, 67% underwent second‐line therapy, while 33% received third‐line or subsequent treatments. Proton‐pump inhibitors ( PPIs ) were administered at low (40%), standard (10%), and high doses (24%), with vonoprazan used in 26% of cases. The overall eradication rate for second‐line treatment was 74%, with the most common regimen being triple therapy ( PPI + amoxicillin + levofloxacin), achieving 73% eradication for 14 days and 57% for 10 days. Adding bismuth to the 14‐day regimen increased effectiveness to 100% ( p = 0.016). In third‐line therapy, a regimen of PPI ‐bismuth‐tetracycline‐metronidazole yielded an 87% cure rate. The fourth‐line dual therapy with amoxicillin‐vonoprazan achieved 100% eradication, while bismuth‐quadruple therapy showed similar results. Dual therapy with vonoprazan and amoxicillin was also effective in fifth‐line treatments, achieving 100% effectiveness. Mild adverse events occurred in 23% of patients, with nausea being the most common (14%), and compliance was 99%. Conclusion In Brazil, the overall effectiveness of second‐line therapy was suboptimal (< 90%); however, the combination of bismuth‐amoxicillin‐levofloxacin prescribed for 14 days reported successful cure rates. In the third‐line, the classical bismuth‐quadruple therapy with metronidazole‐tetracycline provided acceptable results (87%). Alternatively, dual therapy with vonoprazan and amoxicillin and rifabutin‐based bismuth‐quadruple therapy showed promising results in third‐ and fifth‐line rescue treatment.