LAUSR

BACKGROUND AND AIMS Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, versus standard treatment on H. pylori eradication in the US and Europe. METHODS In a randomized, controlled, phase 3 trial, treatment-naïve adults with H. pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20mg vonoprazan twice daily [BID]; 1g amoxicillin three times daily), or double-blind triple therapy BID (vonoprazan 20mg or lansoprazole 30mg; amoxicillin 1g; clarithromycin 500mg) for 14 days. The primary outcome was non-inferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (non-inferiority margin=10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients. RESULTS 1,046 patients were randomized. Primary outcome eradication rates (non-resistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, versus lansoprazole triple therapy 78.8% (both non-inferior; difference 5.9% [95% CI -0.8-12.6] P < .001; difference -0.3% [95% CI -7.4-6.8] P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, versus lansoprazole triple therapy 31.9% (both superior; difference 33.9% [95% CI 17.7-48.1] P = .001; difference 37.7% [95% CI 20.5-52.6] P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, versus 68.5%, difference 12.3% [95% CI 5.7-18.8] P = .001; difference 8.7% [95% CI 1.9-15.4] P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05). CONCLUSION Both vonoprazan-based regimens were superior to PPI-based triple therapy in clarithromycin-resistant strains and in the overall study population. CLINICALTRIALS gov; NCT04167670.