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

BACKGROUND: 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. AIM: 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: Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to 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 to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. RESULTS: Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance 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 or adverse events occurred between groups. CONCLUSION: One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.

Metal-Free N-Formylation of Amines with CO2 and Hydrosilane by Nitrogen-Doped Graphene Nanosheets.

N-Formylation of amines with carbon dioxide (CO2) as a carbonyl source is emerging as an important way for CO2 transformation into high-value-added chemicals; however, the developed catalytic systems mainly focused on transition-metal-based homogeneous catalysts. Herein, we reported rationally designed nitrogen-doped graphene nanosheets (NG) as metal-free catalysts for N-formylation of various amines with CO2 and hydrosilane to formamide under mild conditions. The NG catalyst displayed a wide amine scope with the desired formamide yields up to >99%, demonstrating its comparable catalytic performance to the reported transition-metal-based catalysts. Our experimental research reveals that the N-formylation of aniline involves an initial NG-promoted CO2 hydrosilylation with PhSiH3 to silyl formate and a subsequent nucleophilic attack of the aniline to give N-formanilide. Moreover, the key step of CO2 hydrosilylation can be simplified to a pseudo-first-order reaction under a high CO2 concentration with an observed reaction rate constant (kobs) of 226 h-1 at 40 °C and an apparent activation energy (Ea) of 34 kJ mol-1. In sharp contrast, a kobs of 23 h-1 and Ea of 47 kJ mol-1 were observed under catalyst-free conditions. Our theoretical investigation indicates that NG-promoted CO2 hydrosilylation corresponds to an exergonic reaction (ΔG = -0.53 eV), which is much lower in energy state than that of catalyst-free conditions (ΔG = -0.44 eV). Finally, the NG showed outstanding recyclability in the N-formylation reaction with almost unchanged catalytic performance during twelve-time recycling. This research thus represented a breakthrough in metal-free transformation of CO2 into fine chemicals with low-cost, environment-friendly, and carbon-based catalysts to replace the scarce and expensive transition-metal-based catalysts.