Efficacy of Tetracycline Three Times Daily was Comparable to That of Four Times Daily for Helicobacter pylori Rescue Treatment: A Multicenter, Noninferiority, Randomized Controlled Trial

ABSTRACT Background The optimal dosage of tetracycline remains unclear for Helicobacter pylori eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for H. pylori infection. Methods A total of 406 patients needing H. pylori rescue treatment were enrolled. Patients were randomized into two groups and received bismuth‐containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET‐T group) or four (TET‐F group) times daily. At least 6 weeks after treatment completion, a 13 C‐urea breath test was performed to evaluate H. pylori eradication. Results The intention‐to‐treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) ( p = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) ( p = 0.841), and the per‐protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) ( p = 0.851) in the TET‐T group and TET‐F group, respectively. The eradication rates for the TET‐T group were not inferior to those of the TET‐F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET‐T group than in the TET‐F group (23.65% vs. 33.50%, p = 0.028). No significant differences were observed in treatment compliance between the groups. Conclusions The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth‐containing quadruple therapy achieved a high eradication rate in H. pylori rescue treatment.