A Comparative Study of Sequential Therapy and Standard Triple Therapy for Helicobacter pylori Infection: A Randomized Multicenter Trial

OBJECTIVES: Studies conducted in large populations of patients and providing full information on Helicobacter pylori (H. pylori) antibiotic resistance are needed to determine the efficacy of sequential therapy (SQT) against this pathogen. This study compared eradication rates with SQT and standard triple therapy (STT), and evaluated the impact of antibiotic resistance on outcomes. METHODS: The study population included adults with positive H. pylori culture presenting at four centers in China between March 2008 and December 2010. Patients were randomly assigned to 10 days of treatment with esomeprazole, amoxicillin, and clarithromycin (STT; n=140) or to 5 days of treatment with esomeprazole and amoxicillin, followed by 5 days of esomeprazole, clarithromycin, and tinidazole (SQT; n=140). Eradication was assessed 8 -12 weeks after treatment. RESULTS: There was no significant difference between the eradication rates achieved with STT (66.4 % (95 % confidence interval (CI) 59.3-74.3)) and SQT (72.1% (65.0-79.3); P=0.300) in either the intention-to-treat analysis or the per-protocol analysis (72.7 % (65.6-79.7) and 76.5 % (69.7-83.3), respectively; P = 0.475). Clarithromycin resistance (CLA-R, odds ratio (OR) = 8.34 (3.13-22.26), P < 0.001) and metronidazole resistance (MET-R, OR = 7.14 (1.52-33.53), P = 0.013) both independently predicted treatment failure in the SQT group. Patients in the SQT group with dual CLA-R and MET-R had a lower eradication rate (43.9 %) than those with isolated CLA-R (88.9 %, P=0.024) or isolated MET-R (87.8 %, P<0.001). CONCLUSIONS: H. pylori eradication rates with STT and SQT were compromised by antibiotic resistance. SQT may be suitable in regions with high prevalence of isolated CLA-R, but it is unsatisfactory when both CLA-R and MET-R are present.