| Background:Helicobacter pylori infection and related diseases are a serious health problem in China.At present,the eradication rate of proton-pump inhibitor(PPI)+ bismuth-based quadruple therapy which was recommended by Chinese guideline is 79.5%-86.6%.This is not meeting the requirement for eradication rates higher than 90%.It is a major problem that how to eradicate Helicobacter pylori effectively for clinicians around the world.In recent years,vonoprazan which is a new acid blocker has shown to produce a stronger acid-inhibitory effect than PPIs.More and more foreign studies showed that 7-day triple therapy based on vonoprazan has a higher eradication rate than 7-day quadruple therapy based on PPI + bismuth.However,due to the differences in the Helicobacter pylori strains and human race,foreign experience may not be applicable in China.Besides,the effectiveness of the triple therapy in the Chinese population is not clear.At the same time,in view of the prevalence of Helicobacter pylori-resistant strains in China,the Chinese guideline requires that the duration of treatment for Helicobacter pylori eradication should be 14 days,while no study focused on the efficacy and safety of the 14-day triple therapy based on vonoprazan.In addition,the mechanism of the high eradication rate of the triple therapy is still unclear,and whether vonoprazan has a direct effect on Helicobacter pylori is unknown.Therefore,it is very necessary to carry out a clinical trail and an in vitro experiment.Objective:To compare the efficacy,safety,and medical compliance of Helicobacter pylori eradication between a 14-day triple therapy based on vonoprazan and a quadruple therapy based on PPI + bismuth in the Chinese population.To compare the socioeconomic differences between different eradication plans.To explore whether vonoprazan has direct inhibitory effect on Helicobacter pylori and the possible mechanism through the vitro experiment.Methods:Clinical trail: From June 1,2021 to January 31,2022,a single-center,prospective,open-label clinical randomized controlled study was conducted at our hospital.All patients confirmed to be infected with Helicobacter pylori were randomly divided into four cohorts(cohort1-cohort 4),receiving vonoprazan+ doxycycline + furazolidone,vonoprazan + doxycycline + amoxicillin,esomeprazole + bismuth +doxycycline + furazolidone and esomeprazole + colloidal bismuth +doxycycline + amoxicillin for 14 days.Lack of informed consent was the main exclusion criterion.Patients were followed up on day 1 and week 5after the end of treatment.The content of the first follow-up mainly included evaluating the medication compliance through the Morisky Medication Adherence Scale-8(MMAS-8)and the numbers of the taken pills and whether the patient had any related adverse event.The second follow-up mainly included the re-examination after Helicobacter pylori treatment.The eradication rates,medication compliance,and adverse event rates for each cohort were analyzed by modified intention-to-treat population(MITT)analysis and per-protocol analysis(PP).At the same time,the main factors affecting the eradication rate were analyzed according to the patient’s demographic characteristics,treatment,and medication compliance.Socioeconomic evaluation: According to the data of clinical trail,the costs of the patients enrolled in the study were collected.The cost-effectiveness ratio and the incremental cost-effectiveness ratio were evaluated.In vitro experiment: The minimum inhibitory concentration(MIC)of Helicobacter pylori SS1 treated with different concentrations of vonoprazan and esomeprazole was detected by agar dilution method.According to the MIC results,the Helicobacter pylori treated with appropriate concentration was selected for transcriptomic sequencing.The main terms or pathways affected by different drugs were explored through GO analysis and KEGG analysis,and the most obvious or interesting differential genes were selected to verify the transcriptomic sequencing results through the Quantitative Real-time PCR(q RT-PCR).Results:1.Clinical trail: There was no statistical difference in the baseline of patients included in each cohort.In the MITT analysis,the eradication rate of Helicobacter pylori in each cohort was 88.13%,87.50%,80.00%and 75.00%.In the PP analysis,the eradication rate of Helicobacter pylori in each cohort was 97.92%,96.55%,91.43% and 90.23%.The eradication rate of cohort 1 and cohort 3 was significantly higher than those in cohort 2 and cohort 4 in both MITT analysis and PP analysis.There were no significant differences in MMAS-8 scale scores among the four cohorts.There were no significant differences in the incidence of related adverse events among the four cohorts.Treatment and medication compliance were the most important factors affecting the eradication rate of Helicobacter pylori.2.Socioeconomic evaluation: The cost-effectiveness ratio of patients in each cohort was 7.18 yuan,7.37 yuan,9.07 yuan and 9.38 yuan.Compared with cohort 1,the incremental cost-effectiveness ratio of the other cohorts was 6.67 yuan,19.57 yuan,and 18.74 yuan.3.In vitro experiment: vonoprazan has no direct inhibitory effect on Helicobacter pylori,and its MIC is above 200μg/ml.Esomeprazole has a direct inhibitory effect on Helicobacter pylori,and its MIC ranges from40μg/ml to 200μg/ml.Both GO analysis and KEGG analysis showed that the genes related to the ribosome were significantly down-regulated after esomeprazole treatment.The q RT-PCR result showed that the ptl G gene which expresses Type IV secretion system protein was a differentially down-regulated gene in the vonoprazan group compared with the control group,and the rpl L gene which expresses 50 S ribosome and ure B gene which expresses urease were differentially down-regulated genes in the esomeprazole group compared with the control group.The sequencing results were accurate and reliable based on the q RT-PCR result.Conclusion:1.In the Chinese population,the eradication rate of Helicobacter pylori in the 14-day triple therapy based on vonoprazan was significantly higher than the eradication rate in the 14-day quadruple therapy based on PPI+bismuth.There was no significant difference in the incidence of adverse events.2.The cost-effectiveness ratio of the 14-day triple therapy based on vonoprazan is lower than that of the 14-day quadruple therapy based on PPI+bismuth.And the use of vonoprazan + doxycycline + furazolidone is the treatment with the lowest cost-effectiveness ratio.3.Vonoprazan has no direct inhibitory effect on Helicobacter pylori.Esomeprazole has obvious bacteriostatic effect on Helicobacter pylori,and its bacteriostatic ability is related to the concentration of esomeprazole.Esomeprazole may inhibit Helicobacter pylori by inhibiting the ribosome synthesis. |
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