Randomised controlled trial: susceptibility-guided therapy versus empiric bismuth quadruple therapy for first-line Helicobacter pylori treatment

Abstract

Background: Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. Aim: To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance. Methods: We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s. Primary outcome was H pylori eradication. Results: Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI −3.1% to 3.2%) and 6.2% intent-to-treat (−0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates. Conclusions: Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.