The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.~Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.~Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy. Eradication status will be determined by 13C-urea breath test at least 6 weeks after eradication therapy. The stool samples will be collected before, and 2 and 8 weeks and 1 year after eradication therapy to analyze the changes in the antibiotic resistance and microbiota of gut flora. The body weight, waist and hip circumference and serum lipid profile, sugar, and HbA1C levels will also be collected before and 2 weeks, 8 weeks and 1 year after eradication therapy.~Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.~Secondary End Points: the eradication rate according per protocol analysis and the adverse effects~Secondary End Point:~(A) Eradication rate according to per protocol analysis (PP analysis) (B) Frequency of adverse effects (C) The changes in the gut microbiota, antibiotic resistance of the Enterobacteriae, metabolic parameters before and after H. pylori eradication (D) The long term eradication rate and reinfection rate
The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.~Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.~Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy.~Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.