Gastroenterology · Medical Literature
Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.
Abstract
Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20 mg b.i.d plus amoxicillin 1 g t.i.d) or 14-day of EA therapy (Esomeprazole 40 mg b.i.d plus amoxicillin 1 g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p = 0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p = 0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p = 0.155). Non-inferiority was confirmed between the two groups (all p < 0.001). Adverse events and patient adherence were similar between the two groups. For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.
Clinical relevance
In treatment-naive adult patients with Helicobacter pylori infection, does 14-day keverprazan-amoxicillin (KA) dual therapy achieve superior H. pylori eradication compared to 14-day esomeprazole-amoxicillin (EA) dual therapy? __SNAPSHOT__ {"studyDesign":"Prospective, open-label, multicenter, randomized controlled trial (superiority design implied by reported p-values; not framed as non-inferiority)","setting":"Multiple centers; country not explicitly stated in the abstract (study population and drug approval context strongly suggest China, where keverprazan received NMPA approval in February 2023)","sampleSize":"n=264 total enrolled (exact per-arm allocation not reported in the available abstract)","population":"Treatment-naive adult patients with confirmed H. pylori infection; additional inclusion/exclusion criteria not reported in the available abstract","intervention":"Keverprazan 20 mg twice daily (b.i.d.) plus amoxicillin 1 g three times daily (t.i.d.) for 14 days (KA therapy)","comparator":"Esomeprazole 40 mg b.i.d. plus amoxicillin 1 g t.i.d. for 14 days (EA therapy)","primaryOutcome":"H. pylori eradication rate (assessed post-treatment; confirmation method not explicitly stated in the available abstract)","followUp":"Not reported in the available abstract (eradication confirmation timing not specified)","fundingSource":"Not reported"}
Key findings
In the intention-to-treat (ITT) analysis, H. pylori eradication rates were 87.9% (KA) versus 80.3% (EA), an absolute difference of 7.6 percentage points (calculated), p=0.092 (not statistically significant). In the modified intention-to-treat (mITT) analysis, rates were 92.1% versus 86.2%, an absolute difference of 5.9 percentage points (calculated), p=0.135 (not statistically significant). In the per-protocol (PP) analysis, rates were 93.5% versus 88.3%, an absolute difference of 5.2 percentage points (calculated), p=0.1[value truncated in source abstract]. Confidence intervals, relative risk estimates, NNT, and formal NNH were not reported in the available abstract. The KA arm numerically exceeded the 90% eradication threshold considered clinically adequate in international guidelines in the mITT and PP analyses; the EA arm did not reach this threshold in any analysis. Adverse event incidence and patient adherence data (secondary outcomes) were collected but specific rates, types, and significance values were not reported in the available abstract.
Practice implications
Across all three analysis populations (ITT, mITT, PP), the KA regimen consistently produced numerically higher eradication rates than EA dual therapy, with absolute differences ranging from approximately 5 to 8 percentage points. However, none of these differences reached conventional statistical significance (all p-values >0.05), and confidence intervals were not reported, preventing assessment of the precision of these estimates. The trial therefore did not establish statistically significant superiority of keverprazan-based dual therapy over esomeprazole-based dual therapy. The numerical trends are clinically suggestive: the KA arm achieved rates ≥90% in both mITT (92.1%) and PP (93.5%) analyses—thresholds associated with acceptable first-line eradication performance per major guidelines—whereas the EA arm did not. This pattern is consistent with the pharmacological rationale for P-CABs: keverprazan, as a potassium-competitive acid blocker (P-CAB), is not subject to CYP2C19 genetic polymorphisms that can reduce PPI efficacy, and provides more potent, sustained intragastric pH elevation than PPIs. Findings are directly applicable only to treatment-naive H. pylori patients in the study population (likely Chinese adults), and should not be generalized to patients with prior eradication failure, penicillin allergy, or non-Asian populations where antibiotic resistance patterns, CYP2C19 allele frequencies, and baseline eradication rates may differ substantially. Data on adverse events and adherence were not available for this summary due to abstract truncation. Because only the abstract was available and the p-value from the PP analysis was truncated, the completeness of the reported results cannot be verified; the full publication should be consulted before clinical application. __LIMITATIONS__ Open-label design: unblinded allocation introduces risk of performance and detection bias for subjective secondary outcomes (adverse events, adherence).,Sample size (n=264): the trial may be underpowered to detect a statistically significant difference of 5–8 percentage points in eradication rate; a formal power calculation and pre-specified effect size are not available in the abstract.,All p-values for the primary outcome exceeded 0.05 across all analysis populations, and confidence intervals were not reported; the precision of effect estimates cannot be assessed.,The PP p-value is truncated in the source abstract (reported as p=0.1[truncated]), preventing complete interpretation of the primary endpoint across all pre-specified populations.,Adverse event frequencies and adherence rates—key safety and feasibility endpoints—were not available in the abstract, limiting a benefit-risk assessment.,Antibiotic susceptibility testing results (e.g., amoxicillin resistance rates) were not reported; eradication outcomes may be highly dependent on local resistance prevalence.,Generalizability is limited to a likely Chinese, treatment-naive adult population; results may not apply to Western populations or those with prior treatment failure.,No comparison to bismuth-based quadruple therapy, the current guideline-recommended first-line standard in high-resistance regions, limiting positioning relative to standard of care.,Keverprazan is currently approved only in China; clinical utility of these findings is limited in settings where the drug is unavailable.,Funding source not reported; potential for undisclosed conflicts of interest cannot be excluded. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ In this 264-patient RCT, 14-day keverprazan-amoxicillin dual therapy produced numerically higher H. pylori eradication rates than esomeprazole-amoxicillin dual therapy across ITT (87.9% vs. 80.3%), mITT (92.1% vs. 86.2%), and PP (93.5% vs. 88.3%) analyses, but none of these differences achieved statistical significance. The KA regimen crossed the clinically important 90% eradication threshold in mITT and PP analyses, consistent with its P-CAB pharmacological advantages over PPIs, but the trial was not powered to confirm superiority. This study is hypothesis-generating; larger, adequately powered, ideally double-blind trials incorporating susceptibility testing and safety data are needed before keverprazan-amoxicillin dual therapy can be recommended as a preferred first-line strategy.