A randomized trial assessed the efficacy and safety of high-dose dual therapy with vonoprazan and amoxicillin (VHA), standard-dose dual therapy with vonoprazan and amoxicillin (VA), and bismuth-based (B) quadruple therapy as first-line treatments in 375 patients with Helicobacter pylori infection. One hundred twenty-five received 20 mg of vonoprazan twice per day and 750 mg of amoxicillin four times per day (VHA group), 125 received 20 mg of vonoprazan twice per day and 1,000 mg of amoxicillin twice per day (VA group), and 125 received B-quadruple therapy with esomeprazole (20 mg), colloidal bismuth pectin capsule (200 mg), amoxicillin (1,000 mg), and clarithromycin (500 mg), all given twice per day. All treatments lasted 10 days. VHA was noninferior to B-quadruple therapy for eradication rates at four or more weeks.
The study was published in the April American Journal of Gastroenterology. The following commentary by Duncan J. Flynn, MD, and Joseph D. Feuerstein, MD, was published in the ACP Journal Club section of the May Annals of Internal Medicine.
Vonoprazan is a novel potassium-competitive acid blocker that blocks the availability of potassium to hydrogen-potassium ATPase. It is more potent and longer acting than PPIs [proton-pump inhibitors]. Qian and colleagues investigated vonoprazan plus high-dose amoxicillin as H pylori therapy, providing another option in a disease with high prevalence and growing resistance rates. Nonetheless, there are factors to consider before adopting this combination as a first-line therapy.
The trial was a randomized, nonblinded, noninferiority, single-center study. A noninferiority design was used to show that VHA-dual therapy is not worse than B-quadruple therapy for eradicating H pylori in this patient population, and lack of blinding is unlikely to influence the eradication rate. However, trials in different patient populations (e.g., non-Asian patients and those with higher body mass index) would be useful to support generalizability of the results.
The option of a different first-line treatment for H pylori remains intriguing. In Qian and colleagues' trial, only the VHA-dual group that included vonoprazan twice daily and amoxicillin 4 times/d showed similar efficacy to B-quadruple therapy. The groups had similar medication adherence rates despite 4 times/d dosing in the VHA-dual group. However, in clinical practice 4 times/d dosing regimens are associated with much lower adherence rates than twice-daily dosing regimens. Although B-quadruple therapy is dosed partly before and partly after meals, dosing is still around a single time setting compared with 4 discrete times that may affect adherence. The 2-drug VHA-dual regimen has a potential advantage over a 4-drug regimen because it reduces the number of potential drug–drug interactions. In the trial, B-quadruple therapy provoked more adverse events than dual therapy, but the difference was mostly due to abnormal taste events and did not influence overall adherence. Finally, cost may be a consideration if VHA-dual therapy outcomes are not superior because VHA-dual pricing is probably higher than PPI pricing.
VHA-dual therapy provides another viable and promising option for H pylori eradication, although replicating the findings in more diverse patient populations would provide additional reassurance about widespread use.