Efficacy Of Different Acid Blockers In Quadruple Therapy And Modified Concomitant Therapy For Helicobacter Pylori Infection

Background:The infection rate of Helicobacter pylori(H.pylori)and disease burden is high in China.Studies have shown that H.pylori infection is associated with many kinds of gastrointestinal diseases and extra-gastric diseases.The current guidelines recommend eradication therapy for H.pylori-infected patients,and the recommended regimens include Clarithromycin-based bismuth-containing quadruple therapy(C-BQT).Effective gastric acid suppression is an important factor in the eradication therapy.Compared to traditional Proton pump inhibitors(PPIs),Potassium-competitive acid blockers(P-CAB)are not affected by cytochrome P450 enzymes(CYPs),thus P-CAB has been gradually used in the eradication treatment of H.pylori.In first-line treatment,whether P-CAB can achieve higher eradication rate,better safety than traditional PPI is still unclear.The increase of antibiotic resistance decreased the eradication rate of H.pylori.Refractory H.pylori refers to patients who fail after three or more times of treatment failure.An ideal eradication therapy is urgently needed.The experience of concomitant therapy suggested that the combined use of three antibiotics can overcome the antibiotic resistance.The low antibiotic resistance of amoxicillin,furazolidone and tetracycline makes it a promising eradication therapy of refractory H.pylori.Therefore,this study focused on the treatment of H.pylori,the aims of this study were as follows:(1)to compare the efficacy,safety and compliance of traditional PPI and P-CAB for C-BQT eradication of H.pylori;(2)to evaluate the efficacy,tolerability and compliance of 14-day modified concomitant therapy in the treatment of refractory H.pylori.Materials and Methods:Part 1:This study retrospectively enrolled patients with H.pylori infection who received C-BQT.According to the type of acid blockers,they were divided into traditional PPI group and P-CAB group.Traditional PPI group which were divided into lansoprazole group and esomeprazole group.The eradication rate,safety and compliance of H.pylori in different treatment regimens were evaluated.Multivariate analysis was performed to identify predictors of eradication failure.Part 2:This study prospectively enrolled patients if they had failed at least three rounds of H.pylori therapies.They received 14-day modified concomitant therapy including esomeprazole 40mg bid,amoxicillin 1000mg bid,furazolidone 100mg bid and tetracycline 500mg qid.The efficacy,compliance,safety of modified concomitant therapy was evaluated.Results:Part 1:A total of 670 patients were included in the study,500 patients in the traditional PPI group and 170 in the P-CAB group.To minimize the potential confounding and selection bias,we used propensity score matching(PSM)to determine the two groups.Among the 340 patients(170 in each group),the eradication rates in the traditional PPI group and P-CAB group were 87.6%(149/170)and 88.8%(151/170)(P=0.736)in Intention to treat analysis(ITT analysis),90.9%(149/164)and 93.2%(151/162)(P=0.432)in Modified ITT analysis(MITT analysis),91.1%(144/158)and 94.1%(144/153)(P=0.316)in Per protocol analysis(PP analysis).The non-inferiority of P-CAB to PPI was confirmed(P<0.001 in ITT,MITT,and PP analyses).In traditional PPI group,there were 329 in the lansoprazole group,171 in the esomeprazole group.After PSM,160 patients for each group were selected.No significant differences were observed between the eradication rates of the two groups.Both traditional PPI group and P-CAB group had low incidence of adverse effects and good compliance.Regression analysis showed that poor compliance was independent risk factor for eradication failure.Part 2:In total,fifty patients received 14-day modified concomitant therapy.The overall eradication rates of modified concomitant therapy were 86%and 91.5%in ITT analysis and PP analysis.Incidences of adverse events was 34%(17/50).No serious adverse events were reported.H.pylori was successfully cultured in 75%(12/16)of the patients,the resistance rates of clarithromycin,metronidazole,levofloxacin were 50%(6/12),91.7%(11/12),58.3%(7/12).All specimens were sensitive to amoxicillin,furazolidone,and tetracycline.Conclusions:Part 1:Both traditional PPI and P-CAB can achieve a high eradication rate in C-BQT.P-CAB was non-inferior to PPI in C-BQT..Both regimens had good safety and compliance.No significant differences were observed between the eradication rates of lansoprazole group and esomeprazole group.Poor compliance was independent risk factor for eradication failure.Part 2:In refractory H.pylori infection,14-day modified concomitant therapy consisting of esomeprazole,amoxicillin,furazolidone and tetracycline can achieve effective eradication rate.Good eradication rate,compliance and tolerance make it an optional choice for refractory H.pylori.