Effectiveness of Classic Triple Therapy Compared with Alternative Regimens for Eradicating H. pylori: A Systematic...

Background: Helicobacter pylori infection is associated with peptic ulcer disease, chronic gastritis, and gastric cancer. Classic triple therapy (CTT) has been widely used, but increasing antibiotic resistance has reduced its effectiveness. Objectives: To evaluate the effectiveness of CTT compared with alternative regimens and to summarize adverse events and adherence. Methods: We searched PubMed, Scopus, Web of Science, and Cochrane Library from January 2000 to March 2025. Randomized trials and observational studies assessing eradication rates were included. Two reviewers independently screened the studies, extracted data, and assessed bias using Cochrane RoB or the Newcastle-Ottawa Scale. Outcomes included eradication rate, adverse events, and adherence. Results: Thirteen studies (n = 3490) were included. CTT eradication rates ranged from 61.9% to 88.8%. Sequential, bismuth-based quadruple and high-dose PPI regimens achieved higher rates (>90% in several trials). Adverse events were mild-moderate and most frequent in quadruple therapy, though adherence remained >90%. Evidence certainty varied (moderate to low in most comparisons). Geographic variation in resistance limited generalizability. Conclusions: CTT is less effective in high-resistance regions. Quadruple, sequential, and high-dose PPI regimens provide superior outcomes. Region-specific treatment guided by susceptibility testing is recommended. Registration: Not registered.