A Randomized Controlled Trial of Triple Therapy Versus Sequential Therapy Versus Concomitant Therapy as First Line Treatment for Helicobacter Pylori Infection

Background Helicobacter pylori is a common infection in Singapore with an overall seroprevalence rate of 31%. The prevalence rate increases with age and exceeds 70% among those more than 65 years of age (1). H pylori is a major pathogen and is associated with development of peptic ulcer disease and gastric malignancies and successful H. pylori eradication has been shown to be important for both primary and secondary prevention of these diseases (2). Triple therapy (TT) comprising proton pump inhibitor (PPI), amoxicillin 1g and clarithromycin 500mg twice daily has long been considered one of the standard treatment for H. pylori infection (2, 3) as initial studies demonstrated success rates of > 90% on per protocol analysis (PP) and > 80% on intention to treat (ITT) analysis . However increasing bacterial resistance, especially to clarithromycin, has been reported and there are concerns that the efficacy of TT has decreased. Sequential therapy (ST) is an alternative first line therapy that consists of 5 days of treatment with a PPI and amoxicillin followed by 5-day treatment with the PPI and clarithromycin and metronidazole. The rationale for this approach is that amoxicillin may weaken the bacterial cell wall in the initial phase of treatment, and prevent the development of drug efflux channels that inhibit clarithromycin from binding to ribosomes and thus help to improve the efficacy of clarithromycin in the second phase of treatment. A recent meta-analysis based on mainly European studies showed that the success rate of ST compared to TT was 92.8 - 96% vs. 76.2 - 78.8% (4). Concomitant therapy (CT) is another alternative first line treatment that consists of 10 days of PPI, amoxicillin, clarithromycin and metronidazole. The rationale for using CT as a first line treatment option is to address the possibility of clarithromycin resistance which is increasingly encountered in clinical practice (5). Currently there are no randomized controlled studies that compared TT with ST in Singapore, although both regimens are being used in routine clinical practice. The hypothesis is that ST is superior to TT as first line treatment for H. pylori infection.

Aim 10-day triple therapy (TT) [twice daily proton pump inhibitors (PPI), amoxicillin 1 g and clarithromycin 500mg] versus 10-day sequential therapy (ST) [5 day PPI and amoxicillin 1g twice daily followed by 5 days PPI, clarithromycin 500mg and metronidazole 400mg twice daily] versus 10-day concomitant therapy (CT) [twice daily PPI, amoxicillin 1g, clarithromycin 500mg and metronidazole 400mg] as first line treatment for H. pylori infection.

Patients and Methods

Study Design:

Prospective randomized controlled study.