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

Abstract

Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line Hpylori treatment in a region with high antimicrobial resistance. We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised Hpylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20mg and amoxicillin 1g b.d. plus clarithromycin 500mg, metronidazole 400mg b.d., or levofloxacin 500mg daily for susceptible infections or bismuth 220mg b.d. and metronidazole 400mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20mg, bismuth 220mg b.d., amoxicillin 1g and metronidazole 400mg t.d.s. Primary outcome was Hpylori eradication. 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. 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.