Clinical Study On Modified Bismuth Quadruple Rescue Therapy For Helicobacter Pylori Eradication

Aims:Helicobacter pylori(H.pylori)infection is associated with a variety of upper gastrointestinal diseases.Successful eradication of H.pylori can benefit for life.However,the problem of H.pylori eradication failure in China is more prominent.It is urgent to have a safe and effective H.pylori rescue therapy.Therefore,the first part of this study will evaluate the efficacy and safety of high-dose amoxicillin-containing modified bismuth quadruple regimen.In addition,there is no consensus on the implementation of H.pylori screen-and-treat strategy in Chinese asymptomatic populations.Therefore,the second part of this study will use the Markov model to present a health economic evaluation of H.pylori screen-and-treat strategies for the prevention of H.pylori-related diseases.Methods:In the first part,312 patients who failed of H.pylori eradication at least twice were assigned.They were randomly divided into two groups:lansoprazole 30mg bid,bismuth potassium citrate 600mg bid,metronidazole 400mg qid,amoxicillin1000mg tid(in amoxicillin group)or tetracycline 500mg qid(in tetracycline group)for14 days.Antibiotic susceptibility was determined by the agar-dilution method.H.pylori eradication was assessed by ¹³C-urea breath test at least 6 weeks after treatment.In the second part,the Markov model was established based on the natural course of H.pylori infection to H.pylori-related diseases(dyspepsia,peptic ulcer,gastric cancer).Markov model inputs were derived from literature searching and expert consultation.The long-term cost and effect of H.pylori screen-and-treat strategy and non-intervention strategy in Chinese asymptomatic population from 20 to 29 years old were compared.First,cost-effectiveness analysis were used to evaluate whether H.pylori screen-and-treat strategy is superior to non-intervention strategy,and then one-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the robustness of Markov model and the uncertainty of parameters.Results:In the first part of the study,the H.pylori eradication rates in amoxicillin group and tetracycline group were 88.5%(138/156)and 87.2%(136/156)in intention-to-treat analysis,93.7%(133/142)and 95.3%(122/128)in per-protocol analysis,92.6%(138/149)and 90.7%(136/150)in modified intention-to-treat analysis,respectively.There was no significant difference in the eradication rate between the two groups(p>0.05),and the eradication rate of the amoxicillin group was not inferior to that of the tetracycline group.The resistance rates of H.pylori to amoxicillin,tetracycline and metronidazole were 8.3%,1.0%and 87.8%,respectively.Metronidazole resistance did not affect the eradication rate of either amoxicillin or tetracycline group(p>0.05).Compared with the tetracycline group,the amoxicillin group had higher compliance and less adverse events.In the second part of the study,baseline analysis showed that the incremental cost-effectiveness ratio of H.pylori screen-and-treat strategy in dyspepsia,peptic ulcer,gastric cancer and integrated Markov model was?146,590/Quality adjustment life year(QALY),?173,343/QALY,?21,219.3/QALY,and?18,116.0/QALY.Sensitivity analysis showed that three Markov models of dyspepsia,peptic ulcer,and gastric cancer were sensitive to some parameters,and H.pylori-related disease integrated Markov model was very robust and was not sensitive to all parameters.Conclusions:The modified bismuth-containing quadruple therapy with metronidazole and amoxicillin is an alternative to classical bismuth quadruple therapy for H.pylori rescue therapy as it provides similar eradication rate with superior safety and compliance.Compared with the non-intervention strategy,H.pylori screen-and-treat strategy in 20 to 29-year-old Chinese asymptomatic population for the comprehensive prevention of three H.pylori-related diseases(gastric cancer,peptic ulcer,dyspepsia)is more cost-effective.