Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication

Background/Aim One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy. We aimed to verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort. Methods Prospective randomised controlled trial of treatment naive H. pylori patients assigned in a 1:1 ratio to receive either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned each PPI in a 1:1:1 ratio. The study was 80% powered for a non-inferiority margin of 10% based on a postulated 90% eradication rate. Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between vonoprazan and PPI groups. Results Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. About 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates were assessed by intention-to-treat analysis: 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy); difference (95% CI: -0.64 [-8.5 to -7.2]) and by per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy); difference (95% CI: 3.3[-1.8 to -8.5]) confirming the non-inferiority of vonoprazan. Clarithromycin resistance significantly predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p = 0.025. No significant differences in CYP 2C19 genotypes and adverse events occurred between both groups. Conclusion One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.