COMPARISON OF EMPIRICAL THERAPY VERSUS SUSCEPTIBILITY TESTING-GUIDED THERAPY FOR REFRACTORY HELICOBACTER PYLORI INFECTION: A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED, NON-INFERIORY TRIAL

Background and Aims: There is limited evidence to support whether optimized empirical therapy can be an alternative to susceptibility testing guided therapy for patients with refractory Helicobacter pylori (H. pylori) infection defined as failure after two or more eradication attempts. We aimed to assess whether optimized empirical therapy by early use of rifabutin, potent acid inhibitor, and quadruple therapy, is non-inferior to susceptibility testing guided therapy for refractory H. pylori infection.
Methods: We conducted a multi-center, open label, randomized controlled trials in Taiwan. Eligible patients were allocated in a 1:1 ratio to receive either empirical guided therapy or susceptibility testing guided therapy. The minimum inhibition concentrations (MICs) of levofloxacin, metronidazole, tetracycline, rifabutin, and clarithromycin resistance were determined by agar dilution test. Study participants received levofloxacin-based quadruple therapy or bismuth quadruple therapy or rifabutin-based therapy or clarithromycin-based concomitant therapy according to the previous medication history or susceptibility testing (Figure 1). The ¹³C-urea breath test was used to determine the status of H. pylori at least 6 weeks after completing eradication therapy. Eradication rates were analyzed according to intent-to-treat (ITT) andper protocol (PP) analyses. The pre-specified margins for non-inferiority analyses were pre-specified as 9%.
Results: Among 198 patients with refractory H. pylori infection were randomly assigned and underwent post-eradication evaluation, the eradication rates in the empirical guided therapy group and the susceptibility guided therapy group were 83.8% (95% CI: 76.6%-91.1%) versus 83.8% (95% CI: 76.6%-91.1%) in the ITT analysis (p-value=1.000), and were 83.7% (95% CI: 76.4%-91.0%) versus 85.6% (95% CI: 78.6%-92.6%) in the PP analysis (p-value=0.714), respectively (Figure 2). The difference of eradication rate between the MTGT and STGT groups was 0% (95% CI: -8.7%-8.7%, non-inferiority p-value=0.045) by ITT analysis, and was -1.9% (95% CI: -10.5%-6.7%, non-inferiority p-value=0.087) by PP analysis.
Conclusions: Optimized empirical therapy was not inferior to susceptibility testing guided therapy for refractory H. pylori infection.