Esophagus to Small Intestine
Lancet Gastroenterol Hepatol. 2023;8(7):623–34
Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: Two multicenter, open-label, randomized controlled, non-inferiority trials
Background: Helicobacter pylori infection is an important causal factor of gastric cancer and peptic ulcer disease and is associated with immune thrombocytopenic purpura and functional dyspepsia. In H. pylori strains, point mutations in the 23S rRNA and gyrA genes are associated with clarithromycin resistance and levofloxacin resistance, respectively. Whether the efficacy of molecular testing-guided therapy is non-inferior to that of susceptibility testing-guided therapy for H. pylori eradication is unclear. Therefore, the authors aimed to compare the efficacy and safety of molecular testing-guided therapy and traditional culture-based susceptibility testing-guided therapy in first-line and third-line treatment of H. pylori infection.
Methods: They did 2 multicenter, open-label randomized trials in Taiwan. In trial 1 (done at 7 hospitals), treatment-naive individuals infected with H. pylori who were aged 20 years or older were eligible for study inclusion. In trial 2 (done at 6 hospitals), individuals aged 20 years or older who failed treatment after 2 or more eradication therapies for H. pylori infection were eligible for enrolment. Eligible patients were randomly assigned (1:1) to receive either molecular testing-guided therapy or susceptibility testing-guided therapy. The randomization sequence was generated by computer using permuted block randomization with a block size of 4. All investigators were masked to the randomization sequence. Clarithromycin and levofloxacin resistance were determined by agar dilution test for measuring minimum inhibitory concentrations in the susceptibility testing-guided therapy group, and by polymerase chain reaction (PCR) and direct sequencing for detection of 23S rRNA and gyrA mutations in the molecular testing-guided therapy group. Study participants received clarithromycin sequential therapy, levofloxacin sequential therapy, or bismuth quadruple therapy according to the resistance status to clarithromycin and levofloxacin. The 13C-urease breath test was used to determine the status of H. pylori infection at least 6 weeks after eradication therapy. The primary outcome was the eradication rate by intention-to-treat (ITT) analysis. The frequency of adverse effects was analyzed in patients with available data. The prespecified margins for non-inferiority were 5% for trial 1 and 10% for trial 2.
Findings: Between March 28, 2018, and April 23, 2021, 560 eligible treatment-naive patients with H. pylori infection were recruited and randomly assigned to the molecular testing-guided therapy group or the susceptibility testing-guided therapy group in trial 1. Between December 28, 2017, and October 27, 2020, 320 eligible patients with refractory H. pylori infection were recruited and randomly assigned to the molecular testing-guided therapy group or the susceptibility testing-guided therapy group in trial 2. 272 men and 288 women were recruited for trial 1, and 98 men and 222 women were recruited for trial 2. In first-line H. pylori treatment, infection was eradicated in 241 of 280 patients (86%, 95% confidence interval [CI]: 82–90) in the molecular testing-guided therapy group and 243 of 280 patients (87%, 95% CI: 83–91) in the susceptibility testing-guided therapy group by ITT analysis (p = 0.81). In third-line H. pylori treatment, infection was eradicated in 141 of 160 patients (88%, 95% CI: 83–93) in the molecular testing-guided therapy group and 139 of 160 patients (87%, 95% CI: 82–92) in the susceptibility testing-guided therapy group by ITT analysis (p = 0.74). The difference in the eradication rate between the molecular testing-guided therapy group and the susceptibility testing-guided therapy group was -0.7% (95% CI: -6.4–5.0; non-inferiority p = 0.071) in trial 1 and 1.3% (95% CI: -6.0–8.5; non-inferiority p = 0.0018) in trial 2 by ITT analysis. No difference in adverse effects across both treatment groups in trial 1 and trial 2 was found.
Interpretation: Molecular testing-guided therapy was similar to susceptibility testing-guided therapy in first-line therapy and non-inferior to susceptibility testing-guided therapy in third-line treatment of Helicobacter pylori infection, supporting the use of molecular testing-guided therapy for H. pylori eradication.