Clarithromycin Versus Furazolidone For Naive H.pylori Infected Patients In A High Clarithromycin Resistance Area

BackgroundThe increase of antibiotic resistance makes the eradication of H.pylori more difficult.Susceptibility-guided therapy for every patient is unrealistic considering the large number of H.pylori infected people worldwide of whom,especially,many are in developing countries.Therefore,choosing a suitable and effective empirical regimen is the focus of H.pylori treatment.Currently,guidelines have recommended bismuth-containing quadruple therapy(BQT)as a first-line treatment for pylori in areas of high clarithromycin resistances.Clarithromycin-containing BQT(C-BQT,containing PPI,bismuth,amoxicillin and clarithromycin)and furazolidone-containing BQT(F-BQT,containing PPI,bismuth,amoxicillin and furazolidone)are commonly used therapy in clinical practice.However,which of the two treatment options is the best one for patients with H.pylori infection is still unclear.ObjectiveThe purpose of this trial is to compare the efficacy,safety,and cost-effectiveness ratio of two regimens,C-BQT and F-BQT,and two treatment strategies,C-F and F-C,in patients with H.pylori infection by means of randomized controlled crossover trial.Materials and MethodsThe trial comprised two phases.The subjects were randomly assigned to two groups,C-F group and F-C group,via computer-generated sequence.In C-F group,patients received C-BQT in the first phase,those who were still positive for H.pylori infection after the first phase entered the second phase to receive F-BQT as rescue treatment.In F-C group,patients were treated with F-BQT firstly and rescued with C-BQT.C-BQT regimen consisted of lansoprazole 30 mg bid,colloidal bismuth capsules 200 mg bid,amoxicillin 1000 mg bid and clarithromycin 500 mg bid.The F-BQT regimen consisted of lansoprazole 30 mg bid,colloidal bismuth capsules 200 mg bid,amoxicillin 1000 mg bid and furazolidone 100 mg bid.Both C-BQT and F-BQT regimens were administered for 14 days.Patients were asked to record adverse effects and compliance during each regimen in the form of a diary card.13C-urea breath test was performed to assess the effect of treatment at least 6 weeks after each treatment regimen.The primary outcome of this study was the eradication rate of both C-BQT and F-BQT regimens and both C-F and F-C treatment strategies.Compliance,safety and cost-effectiveness were assessed for both regimens and treatment strategies.The risk factors for eradication failure were also analyzed.ResultsA total of 350 patients were finally enrolled with 175 patients in each group.7 patients in C-F group and 7 patients in F-C group were lost to follow up during primary treatment.In the rescue treatment,1 in C-F group and 2 in F-C group dropped out.As first-line treatments,the eradication rates of C-BQT and F-BQT were 89.7%(157/175)and 92.0%(161/175)in the ITT analysis,93.4%(156/167)and 95.8%(161/168)in the PP analysis and 93.5%(157/168)and 95.8%(161/168)in the MITT analysis respectively.As a second-line treatments,the eradication rate of F-BQT was 72.7%(8/11)in the ITT analysis and 80.0%(8/10)in the MITT and PP analysis;the eradication rate of C-BQT was 51.7%(4/7),80.0%(4/5)and 80.0%(4/5)in the ITT,MITT and PP analysis,respectively.There were no statistical differences in eradication rates between the two regimens in both primary and rescue treatments.The cumulative eradication rates of C-F and F-C strategies were 94.3%(165/175)and 94.3%(165/175)in the ITT analysis,98.8%(165/167)and 99.4%(165/166)in the MITT analysis and 98.8%(165/167)and 99.4%(165/166)in the PP analysis,respectively.There were no statistical differences between the eradication rates of the two strategies.The incidence of adverse events was 36.0%and 28.6%for C-BQT and 32.6%and 27.3%for F-BQT in the primary and rescue treatments,respectively,with no significant difference.There were also no significant differences in compliance between the two regimens.Cost-effectiveness index of F-BQT was better than C-BQT as both primary and rescue treatments(0.54 versus 1.24 in primary treatment;0.65 versus 1.45 in rescue treatment).The overall cost-effectiveness indexes were 0.56 in F-C strategy and 1.21 in C-F strategy.Cumulative median cost in C-F strategy($119.27,range 116.32-168.07)is significantly higher than F-C strategy($55.07,range 51.75-168.07).Compliance less than 80%was defined as the risk factor for failure eradication.ConclusionsIn high clarithromycin resistance area,both C-BQT and F-BQT can be recommended as first-line treatments.F-C and C-F strategies can achieve comparably high cumulative eradication rates.F-BQT should be preferred as an empirical therapy for its excellent cost-effectiveness and acceptable safety.In addition,good compliance is an important factor to improve the success rate of H.pylori eradication in patients,and patient education should be enhanced to improve patient compliance for better eradication efficacy.