Objective Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study. Design Double-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and ≤2 years (extension). The following measurements were made: 24-week (primary outcome; double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate, cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment-emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II concentrations. Results The 24-week peptic ulcer recurrence rate was 2.8%, 0.5% and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups, respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin 8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the extension study, peptic ulcer recurrence rates were significantly lower with vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260), compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole compared with two doses of vonoprazan in both 24-week study and extension study. Conclusion Vonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in preventing peptic ulcer recurrence during LDA therapy, had a similar long-term safety profile and was well tolerated. Trial registration numbers NCT01452763; NCT01456247.

Background: Helicobacter pylori eradication containing the potassium-competitive acid blocker, vonoprazan, achieves a higher eradication rate than therapy with proton pump inhibitors (PPIs). Because vonoprazan is mainly metabolized by CYP3A4/5, CYP genotype may affect the eradication rate. We investigated the influence of antibiotic susceptibility and CYP3A4/5 and CYP2C19 genotypes on the eradication rates. Methods: A total of 307 Japanese who were genotyped for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17, and investigated for susceptibility to antimicrobial agents, received vonoprazan-containing regimens: (1) With amoxicillin and clarithromycin as the first-line treatment; (2) with amoxicillin and metronidazole as the second-line treatment; or (3) with amoxicillin and sitafloxacin as the third-line treatment. Results: The eradication rate was 84.5% (95% confidence interval [CI]: 78.9–89.1%) using first-line, 92.6% (95% CI: 82.1–97.9%) using second-line and 87.5% (95% CI: 73.1–95.8%) using third-line treatment. Infection with clarithromycin-resistant strains was a predictive factor for failed eradication (odds ratio: 5.788, 95% CI: 1.916–17.485, p = 0.002) in multivariate analysis. No significant differences were observed in the eradication rate of regimens among CYP3A4, CYP3A5 and CYP2C19 genotypes. Conclusions: Genotyping for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17 before vonoprazan-containing eradication treatment may not be useful for predicting clinical outcomes.

Objective Serological antibody test have been widely performed to detect the presence of H. pylori, but they have not been used to evaluate the status of H. pylori after eradication. In this study we evaluated the diagnostic accuracy of a new serological test kit (E-plate) after eradication. >Method Eradication of H. pylori was performed in 100 patients by proton pump inhibitor (PPI)+amoxicillin (AMPC)+clarithromycin (CAM) or PPI+AMPC therapy. Evaluation of H. pylori was done by culture, histology and rapid urease test before, and 8 weeks after, the treatment. Serological tests were also performed before and after treatment using the E plate. Cure was defined as no evidence of H. pylori at 8 weeks after the treatment. Receiver operating characteristic (ROC) analysis was performed to determine the ideal cut-off value for percentage change in the serological test. Result Success was obtained in 73 patients, failure in 20 patients and there were 7 dropouts. Serological test value was significantly decreased after treatment (44.3±29.6 U/ml) compared to before treatment (94.8±73.2 U/ml) in the successful cases. In contrast, those with no significant change after treatment (62.7±31.3 U/ml) compared to before treatment (72.9±47.7 U/ml) were considered as failure cases. ROC analysis revealed that cut-off values of a 20%, 30%, and 40% decrease on E plate result yielded a sensitivity of 95.5%, 92.4%, 71.2% and a specificity of 73.3%, 84.2%, 94.7%, respectively. Conclusion The new E plate serological test kit for H. pylori was useful for distinguishing success from failure 8 weeks after completion of eradication therapy for H. pylori. (Internal Medicine 41: 780-783, 2002)