Compared Modified Dual Therapy With Bismuth-Containing Quadruple Therapy For Eradicating H.pylori In Treatment-naive Patients

Background and purposeHelicobacter pylori?H.pylori?has been recognized as the main cause of chronic active gastritis,peptic ulcer,gastric adenocarcinoma and gastric mucosa associated lymphoid tissue lymphoma?MALT lymphoma?.H.pylori-associated gastritis is an infectious disease,and the eradication of H.pylori can prevent gastric cancer.The prevalence of H.pylori is high in China.Therefore,it is urgent to treat H.pylori infection.Because China is one of highly resistant regions of clarithromycin,14 days of Bismuth-containing quadruple therapy?BQT?are recommended as the first choice for experience treatment in Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection.But BQT has limitations,such as increasing side effects mainly associated with the use of bismuth,poor compliance with medication use,high drug cost,increased the complexity of drug regimens,high rates of resistance to clarithromycin,inaccessibility of bismuth in some areas.Moreover,if the quadruple therapy fails,secondary resistance increases,and rescue treatment regimens has limited.The global resistance rate of amoxicillin remains at a lower level.PPI and amoxicillin dual therapy were proposed in1980s.Amoxicillin has proven to be pH-dependent and time-dependent.It can achieved a high H.pylori eradication rate at a high intragastric pH level and a high administering frequency.Therefore,modified PPI-amoxicillin dual therapy based on pharmacology and pharmacogenomics were used in clinical practice.In Italy and Taiwan,modified PPI-amoxicillin dual therapy has been reported to be effective.However,studies in the United States and South Korea have shown that the treatment effect of high dose dual therapy was not satisfactory.Therefore,it is worth to explore whether Modified dual therapy?MDT?is similarly effective as BQT when it used as first-line treatment regimen in Chinese population.ObjectiveThe purpose of this study was to compare the efficacy and safety of MDT?esomeprazole+amoxicillin?with BQT?bismuth potassium citrate+esomeprazole+amoxicillin+clarithromycin?for eradicating H.pylori infection in Chinese treatment-naive patients.Besides,we evaluated the adverse events,compliance,medication cost and factors that may affect the rate of eradication.MethodsThis study was a single-center,open-label,randomized,non-inferiority trial.232 cases of H.pylori-infected naive patients(¹³C-Urea breath test,rapid urease test and H.pylori culture were all positive results)were randomly assigned to receive one of the following14-day regimens in a 1:1 ratio:MDT group?esomeprazole 20mg qid and amoxicillin 750mg qid?or BQT group?esomeprazole 20mg bid,amoxicillin 1000mg bid,bismuth potassium citrate 220mg bid,clarithromycin 500mg bid?.Primary outcome was H.pylori eradication rates.ResultsITT,PP,and MITT analysis showed that eradication rates were 87.9%?102/116;95%CI82.0%–93.9%?,91.1%?102/112;95%CI 85.8%-96.4%?,91.1%?102/112;95%CI85.8%-96.4%?in the MDT group.ITT,PP,and MITT analysis showed that eradication rates were 89.7%?104/116;95%CI 84.1%-95.2%??91.2%?104/114;95%CI 86.0%-96.4%??90.4%?104/115;95%CI 85.1%-95.8%?in the BQT group.There were no significant differences in eradication rates between the 2 groups?P=0.677,0.967,and 0.869 in the ITT,PP,and MITT analysis,respectively?.The noninferiority of the MDT group to the BQT group was established?P=0.0228,0.0046,and 0.0028 in the ITT,PP,and MITT analysis,respectively?.The adverse events rate in MDT group was significantly less than that in BQT group?6.3%vs22.8%,P<0.001?.There was no significant difference in compliance between two groups?96.6%vs 98.3%,P=0.683?.The differences in antibiotic resistance and gene polymorphism of CYP2C19 and IL-1B-511 had no significant effect on the eradication rate of two groups.MDT ameliorated effects of variations in CYP2C19 and IL-1B-511genotypes on treatment outcomes.The drug cost in MDT group is less than that in BQT group.ConclusionMDT is not inferior to BQT in the H.pylori-infected treatment-naive patients.Adverse events and medication cost were less in MDT group than that in BQT group.MDT can be used as an empirical first-line treatment for eradicating H.pylori.