We read with interest the recent paper comparing 1 and 2 weeks of triple therapy for Helicobacter pylori infection in patients with duodenal ulcer disease. (Gut 2007;56:475–9) H pylori is an infectious disease and the goal of treatment is to cure the infection. In 2007, one would hope to be able to reliably cure ⩾95% of the treated patients (discussed by Graham et al).1 In 1989, a successful treatment has been defined as one that cures >80% of the patients.2 By 1995, it seemed that 90% was achievable.3 The Maastricht consensus conferences defined a useful therapy as the one with an intention to treat (ITT) cure rate of >80%, which is a relatively low hurdle (ie, those with cure rates of ⩽80% would be unacceptable).5 Although the authors concluded that 7 and 14 days therapy provided essentially equivalent results, the focus should have been on the fact that the cure rates obtained were unacceptably low with either duration (eg, ITT of 79.7 for 7 days and 81.7 for 14 days), especially among patients with duodenal ulcer disease where the cure rates are typically higher than among patients without ulcers.5,6,7,8
Their results are not unexpected as large studies of this legacy triple therapy (proton‐pump inhibitor (PPI), amoxicillin and clarithromycin) have recently yielded unacceptably low eradication rates in Europe and the US, and have only infrequently achieved the minimum 80% success rate (table 1).10,11,12,13,14,15,16,17 Overall, these results suggest that traditional triple therapy should no longer be used in Western populations unless pretreatment susceptibility is confirmed and then it should be used for 14 days.18,19
Table 1 Results of recent large studies with proton‐pump inhibitors, clarithromycin and amoxicillin triple therapy in Europe and the US.
| First author | Total patients (n) | Duration (days) | ITT (95% CI) |
|---|---|---|---|
| Della et al9 | 812 | 7 | 72% (69% to 75%) |
| Bochenek et al10 | 177 | 7 | 65% (56% to 73%) |
| Boixeda et al11 | 890 | 7 | 77% (74% to 80%) |
| Calvet et al8 | 237 | 7 | 76% (73% to 80%) |
| Calvet et al8 | 210 | 10 | 79% (74% to 85%) |
| De Francesco et al10 | 115 | 7 | 71% (63% to 79%) |
| De Francesco et al12 | 116 | 10 | 80% (72% to 87%) |
| Fennerty et al13 | 123 | 10 | 81% (73% to 87%) |
| Fennerty et al13 | 126 | 14 | 82% (73% to 88%) |
| Laine et al14 | 233 | 10 | 77% (71% to 82%) |
| Scaccianoce et al15 | 70 | 7 | 75% (66% to 86%) |
| Scaccianoce et al15 | 71 | 10 | 81% (73% to 91%) |
| Vakil et al16 | 194 | 7 | 77% (71% to 83%) |
| Vakil et al16 | 196 | 10 | 78% (72% to 84%) |
| Vakil et al16 | 206 | 10 | 73% (67% to 79%) |
| Zagari* et al | 301 | 7 | 79% (74% to 83%) |
| Zagari* et al | 301 | 14 | 81% (77% to 85%) |
| Zullo17 | 527 | 7 | 74% (70% to 77%) |
| Zullo17 | 87 | 7 | 80% (72% to 88%) |
*ITT Current study being discussed.
H pylori is a serious, chronic, transmissible infectious disease that causes damage to gastric structure and function, and is a major cause of morbidity and mortality worldwide. All the patients in this study had H pylori‐related ulcer disease, and untreated 10–25% would be expected to develop complications such as haemorrhage. We are concerned about the inclusion of the dual therapy arm of omeprazole and amoxicillin in the trial. The dual therapy at these doses typically yields a cure rate of ⩽50% and is listed under the category of “not recommended”. The manuscript states that the protocol was approved by institutional review boards, and all patients gave informed consent. What was the nature of the informed consent? How was a known ineffective therapy justified to the patients with duodenal ulcer disease and to the review boards? We believe that the information given to patients and the justifications must be described in detail in the publication including what the patients were told, and that they entered the trial knowing that they would have a high chance of treatment failure. Finally, what was done to ensure that the large number of patients with failed treatment subsequently receive appropriate therapy for H pylori‐related duodenal ulcer disease? It may also be good time to rethink current approaches to H pylori treatment.
Acknowledgements
This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338, which funds the Texas Gulf Coast Digestive Diseases Center.
Footnotes
Competing interests: DYG has received small amounts of grant support and/or free drugs or urea breath tests from Meretek, Jannsen/Eisai, TAP, and BioHit for investigator initiated and completely investigator controlled research in the area of H pylori infections. In addition, DYG is a paid consultant for Otsuka Pharmaceuticals and a member of the Board of Directors of Meretek, Diagnostics, the manufacturer of the 13C‐urea breath test. He is also a consultant to Novartis with regards to H pylori vaccine development and also receives royalties on the Baylor College of Medicine patent covering the serologic test, HM‐CAP. YY has no potential conflicts of interest to declare.
References
- 1.Graham D Y, Osato M S, Hoffman J.et al Furazolidone combination therapies for Helicobacter pylori infection in the United States. Aliment Pharmacol Ther 200014211–215. [DOI] [PubMed] [Google Scholar]
- 2.Graham D Y, Klein P D, Opekun A R.et al In vivo susceptibility of Campylobacter pylori. Am J Gastroenterol 198984233–238. [PubMed] [Google Scholar]
- 3.Graham D Y. A reliable cure for Helicobacter pylori infection? Gut 199537154–156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.European Helicobacter Pylori Study Group Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. Gut 1997418–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Broutet N, Tchamgoue S, Pereira E.et al Risk factors for failure of Helicobacter pylori therapy—results of an individual data analysis of 2751 patients. Aliment Pharmacol Ther 20031799–109. [DOI] [PubMed] [Google Scholar]
- 6.Broutet N, Marais A, Lamouliatte H.et alcagA Status and eradication treatment outcome of anti‐Helicobacter pylori triple therapies in patients with nonulcer dyspepsia. J Clin Microbiol 2001391319–1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wong W M, Xiao S D, Hu P J.et al Standard treatment for Helicobacter pylori infection is suboptimal in non‐ulcer dyspepsia compared with duodenal ulcer in Chinese. Aliment Pharmacol Ther 20052173–81. [DOI] [PubMed] [Google Scholar]
- 8.Calvet X, Ducons J, Bujanda L.et al Seven versus ten days of rabeprazole triple therapy for Helicobacter pylori eradication: a multicenter randomized trial. Am J Gastroenterol 20051001696–1701. [DOI] [PubMed] [Google Scholar]
- 9.Della M P, Lavagna A, Masoero G.et al Effectiveness of Helicobacter pylori eradication treatments in a primary care setting in Italy. Aliment Pharmacol Ther 2002161269–1275. [DOI] [PubMed] [Google Scholar]
- 10.Bochenek W J, Peters S, Fraga P D.et al Eradication of Helicobacter pylori by 7‐day triple‐therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double‐blind, randomized studies. Helicobacter 20038626–642. [DOI] [PubMed] [Google Scholar]
- 11.Boixeda D, Martin d A, Bermejo F.et al Seven‐day proton pump inhibitor, amoxicillin and clarithromycin triple therapy. Factors that influence Helicobacter pylori eradications success. Rev Esp Enferm Dig 200395206–215. [PubMed] [Google Scholar]
- 12.De Francesco V, Zullo A, Hassan C.et al The prolongation of triple therapy for Helicobacter pylori does not allow reaching therapeutic outcome of sequential scheme: a prospective, randomised study. Dig Liver Dis 200436322–326. [DOI] [PubMed] [Google Scholar]
- 13.Fennerty M B, Kovacs T O, Krause R.et al A comparison of 10 and 14 days of lansoprazole triple therapy for eradication of Helicobacter pylori. Arch Intern Med 19981581651–1656. [DOI] [PubMed] [Google Scholar]
- 14.Laine L, Frantz J E, Baker A.et al A United States multicentre trial of dual and proton pump inhibitor‐based triple therapies for Helicobacter pylori. Aliment Pharmacol Ther 199711913–917. [DOI] [PubMed] [Google Scholar]
- 15.Scaccianoce G, Hassan C, Panarese A.et alHelicobacter pylori eradication with either 7‐day or 10‐day triple therapies, and with a 10‐day sequential regimen. Can J Gastroenterol 200620113–117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Vakil N, Lanza F, Schwartz H.et al Seven‐day therapy for Helicobacter pylori in the United States. Aliment Pharmacol Ther 20042099–107. [DOI] [PubMed] [Google Scholar]
- 17.Zullo A, Vaira D, Vakil N.et al High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther 200317719–726. [DOI] [PubMed] [Google Scholar]
- 18.Ford A, Moayyedi P. How can the current strategies for Helicobacter pylori eradication therapy be improved? Can J Gastroenterol 200317(Suppl B)36B–440. [DOI] [PubMed] [Google Scholar]
- 19.Calvet X, Garcia N, Lopez T.et al A meta‐analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 200014603–609. [DOI] [PubMed] [Google Scholar]