The Efficacy And Safety Of Bismuth Citrate,bismuth Capsule And Bismuth Granules In H.pylori First-line Eradication

Backgroud:Helicobacterpylori（H.pylori）infection is a global public health problem^[1].Eradication of H.pylori can effectively treat chronic gastritis,peptic ulcer and gastric mucosal associated lymphoma,and reduce the incidence of gastric cancer to a certain extent^[2-4].At present,the main regimen recommended for H.pylori eradication therapy worldwide is a PPI triple regimen consisting of proton pump inhibitor（PPI）combined with antibiotics,that is,one PPI combined with two antibiotics^[5,6].However,with the increasing resistance rate of Hp to commonly used antibiotics,bismuth quadruple therapy（bismuth,PPI combined with two antibiotics）has also been recommended as the first-line regimen in recent years by the international consensus,while The Fifth Chinese national consensus report on the management of H.pylori infection published in 2017 in China recommends bismuth quadruple therapy as the main empirical treatment^[7].At present,commonly used bismuth agents in clinical practice include bismuth citrate and bismuth pectin etc^[8].Pharmaceutical studies have shown that bismuth citrate is a medium molecular weight bismuth,while bismuth pectin is a large molecular weight bismuth.Because bismuth pectin enters the blood very little after oral administration,its plasma concentration is significantly lower than that of bismuth citrate,thus with higher safety^[9].The standard bismuth agent recommended in the Fifth Chinese national consensus report on the management of H.pylori infection is bismuth potassium citrate.The consensus also indicates that pectin bismuth can be used for the eradication of H.pylori,but its optimal dose has yet to be determined^[7].Objective:The aim of this study was to evaluate the efficacy and safety of bismuth pectin capsules and bismuth pectin granules in the first-line quadruple treatment of H.pylori using bismuth potassium citrate capsules as control.Method（s）:This study was a multicenter,randomized,prospective comparative clinical trial.The patients with with H.pylori infection who met the inclusion criteria and visited the outpatient clinics of Xijing Hospital,the First Hospital of Shanxi Medical University,and Gansu Provincial People’s Hospital between May 2020 and December 2020 were selected and randomly divided into four groups in a ratio of 1:1:1:1 to receive a 14-day bismuth quadruple regimen（bismuth according to the specified drug and dose,rabeprazole 10 mg each time,amoxicillin 1000 mg each time,and clarithromycin 500 mg each time,all four drugs twice a day）.Group A was bismuth potassium citrate group,given bismuth potassium citrate capsule 220mg each time;Group B was colloidal pectin-bismuth capsule group,200mg pectin-bismuth capsule was given each time.Group C was colloidal pectin-bismuth granules low-dose group,giving pectin-bismuth granules 150mg each time.Group D was the colloidal pectin-bismuth granules high-dose group,giving pectin-bismuth granules 300mg each time.The primary outcome measure was the eradication success rate of the four treatment regimens,and the secondary outcome measure were the incidence of adverse events,the symptom improvement rate at the end of eradication therapy and 4 weeks after the end of eradication therapy,and patient compliance.Result（s）:A total of 240 patients who met the criteria were included in this study,with 60patients in each group.Among them,9 patients in group A were lost to follow-up,group B one loss due to an anaphylactic reaction,and 3 patients lost to follow-up,there are 6patients were lost to follow-up in group C,group D nine patients lost to follow-up,and 1patients also had an anaphylactic reaction and peels;finally,there are 211 patients completed the follow-up.An intention-to-treat（ITT）analysis showed that the eradication rates of H.pylori in group A,B,C and D were 73.3%（44/60）,76.7%（46/60）,75.0%（45/60）and 71.7%（43/60）,respectively,and there was no significant difference among groups（P>0.05）.According to Per-Protocol（PP）analysis,the eradication rates of H.pylori in groups A,B,C and D were 86.3%（44/51）,82.1%（46/56）,83.3%（45/54）and 86.0%（43/50）,respectively,and there was no significant difference among the four groups（P>0.05）.There was no statistical significance in symptom improvement rate and patient compliance between the four groups at the end of eradication therapy and 4 weeks after eradication therapy,P>0.05.The overall incidence of adverse reactions in group B was lower than that in group A,and the difference between the two groups was statistically significant（P=0.018）,while there was no significant difference in the overall incidence of adverse reactions among groups A,C and D（P>0.05）.Conclusion（s）:Compared with bismuth citrate quadruple regimen,the colloid pectin-bismuth granule and colloid pectin-bismuth capsule quadruple regimen achieved comparable H.pylori eradication efficacy without increased adverse reactions,suggesting that both colloid pectin-bismuth granule and colloid pectin-bismuth granule can be used for the eradication of H.pylori.Moreover,150mg of colloidal pectin-bismuth particles can achieve the same eradication effect as 220mg of bismuth potassium citrate capsules,while the adverse reactions are reduced,which is worthy of clinical promotion.