European Gastroenterology & Hepatology Review, 2008;4(1):72-73
Proton pump inhibitor (PPI) triple therapy – PPI twice daily + clarithromycin twice daily + amoxicillin twice daily – has been recommended as the first-line initial therapy for Helicobacter pylori infection by a recent international consensus group and recent Japanese and US guidelines.1–3 However, there is growing dissatisfaction with this therapy because of the falling eradication rate and the increasing prevalence of clarithromycin resistance worldwide. New therapies are therefore being sought by many investigators; one of these will eventually replace PPI triple therapy.4 Despite this, the safety of PPI triple therapy and its continued efficacy – albeit at a lower rate – are factors that need to be remembered in the development of any new therapy. PPI triple therapy remains the preferred therapy of primary care physicians throughout the world.5,6
Proton Pump Inhibitor Triple Therapy
Although PPI triple therapies are widely used, the duration of therapy has been the subject of debate. A review of controlled trials suggested that 14-day treatment with triple therapy was superior to seven-day treatment (difference 12%, 95% confidence interval [CI] 7–17%).7 The duration of the triple therapy regimen has been the subject of much debate. A recent European study found no difference between one week and two weeks of PPI triple therapy.8 The issue is undecided at the moment, but local factors should determine the duration of treatment.
Bismuth-based Triple/Quadruple Therapy
Bismuth triple therapy (bismuth + metronidazole + tetracycline administered for 14 days) and quadruple therapy (bismuth + metronidazole + tetracycline + PPI administered for seven to 10 days) are alternative treatment strategies in areas where clarithromycin resistance rates are high and metronidazole resistance rates are low. It is also a reasonable choice when cost considerations are important. Bismuth triple therapy has had a small number of enthusiasts who have insisted – based on small trials in single centres – that compliance with this regimen was good and that high success rates could be achieved. This theory was tested in a large randomised controlled trial (RCT) that evaluated bismuth triple therapy administered for 14 days and compared it with seven-day PPI triple therapy and seven-day quadruple therapy.9 Eradication rates were similar for PPI triple therapy (78%) and quadruple therapy (82%), and both were significantly better than 14-day bismuth triple therapy (69%). Moderate to severe adverse events were very common (45%) with bismuth triple therapy, and non-compliance was very high (15%). In another RCT in Spain, seven-day PPI triple therapy was similar to quadruple therapy in terms of the eradication of H. pylori.10
A single-capsule preparation of bismuth biskalcitrate with metronidazole and tetracycline has been developed. Although it decreases the number of pills that needs to be taken, the regimen is still complicated: three tablets need to be taken four times daily and a PPI needs to be taken separately twice daily. Results in the US and Europe have been promising, with an eradication rate of 93% by intent-to-treat analysis in Europe for 10-day therapy and of 87.7% in the US.11,14 In the US trial, the results were comparable to 10-day PPI triple therapy. Due to manufacturing-related issues, the US Food and Drug Administration (FDA) issued a non-approvable letter to the manufacturer in 2002, and the drug is not currently available in the US. It is anticipated that these issues will be resolved in the near future.
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