The addition of bismuth to amoxicillin-vonoprazan (AV) increased the efficacy of the combination in treating Helicobacter pylori infection, and exceeded the eradication rate of clairthromycin-based triple therapy CAR), in a 3-arm multicenter randomized trial.1
"Most current international guidelines recommend 14-day bismuth-containing quadruple therapy or non-bismuth quadruple therapy...as first line treatments, particularly in regions with higher clarithromycin resistance," indicate Ping-I Hsu, MD, Division of Gastroenterology, Department of Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, and colleagues.
"Although these regimens achieve high eradication rates, they involve two or three antibiotics—some of which may be unnecessary—thus increasing the risk of adverse events, drug interactions, and the development of multidrug-resistant H pylori strains," observe Hsu and colleagues of the Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium.
The investigators randomized 390 patients with confirmed H pylori infection 1:1:1 to 14 day treatment with either AV, AV plus bismuth (BAV), or CAR. Presence of H pylori was ascertained by positive results from both the rapid urease test and histology, or by positive culture.Criteria for excluding candidates included prior H pylori eradication treatment, use of antibiotics within the previous 4 weeks, or serious concomitant illness.
The AV dosing was vornoprazan 20mg twice daily and amoxicillin 750mg four times daily; BAV addedtripotassium dicitrato bismuthate 300mg four times daily; and the CAR standard triple therapy comprised rabeprazole 20mg, amoxicillin 1gm, and clarithromycin 500mg twice daily.
The primary endpoint was the H pylori eradication, confirmed by the 13C-urea breath test conducted at least 4 weeks after treatment completion. Adherence to the treatment regimens was verified by pill count.For the intent to treat (ITT) analysis, 33 patients were excluded for either incomplete follow up or inadequate compliance to treatment (10 from BAV group, 10 from AV group and 13 from the CAR group).The investigators noted, however, that the remaining cohort was sufficient to preservestatistical power of the primary analysis.
Hsu and colleagues reported (ITT) rates of H pylori eradication of 93.8% with BAV, 83.9% with AV and 83.1% with CAR treatment regim
What You Need to Know
Adding bismuth to amoxicillin-vonoprazan (BAV) achieved a significantly higher H pylori eradication rate (93.8%) than either amoxicillin-vonoprazan alone (83.9%) or standard clarithromycin-based triple therapy (83.1%), with comparable adverse event rates.
Since global amoxicillin resistance remains under 3%, the authors argue BAV could serve as a simplified first-line regimen that avoids the need for routine pretreatment clarithromycin resistance testing.
The findings suggest clarithromycin-containing regimens may be unnecessary, since mono-antibiotic-based options like AV and BAV can achieve high efficacy while reducing risks of adverse events, microbiota disruption, and multidrug resistance.
ens.BAV was statistically significantly superior to both AV (95% CI, 2.4%-17.6%) and CAR (3.0%-18.4%). Resistance to amoxicillin and to clarithromycin were identified as contributing risk factors for eradication failure with BAV and CAR. The investigators noted that overall adverse event rates were comparable.
The investigators point out that mono-antibiotic regimens offer several advantages over the frequently recommended triple therapy with clarithromycin, amoxicillin, and a proton-pump inhibitor (PPI), including less disruption of gut microbiota, fewer adverse events, and less contribution to development of multidrug resistance.In addition, their results with both AV and BAV suggest that clarithromycin regimens may be unnecessary.
"This randomized controlled trial is the first to demonstrate that the addition of bismuth to AV dual therapy can transform a suboptimal regimen into a highly effective eradication strategy," Hsu and colleagues declare.
"Given that global resistance of H pylori to amoxicillin remains below 3%, BAV triple therapy represents a promising first-line option in most regions and supports a simplified treatment algorithm that does not require routine pretreatment testing for clarithromycin resistance," they concluded.
Reference
1. Hsu P-I, Sheu M-J, Chen C-L, et al. Bismuth-amoxicillin-vonoprazan triple, amoxicillin-vonoprazan dual, and clarithromycin-based triple therapies for first-line treatment of Helicobacter pylori infection: A multicenter, open-label, randomized trial. Helicobacter. 2026: 31:e70131. https://doi.org/10.1111/hel.70131.Accessed September 2, 2026.
