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Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a prospective randomized study

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

Eradication rates following standard triple therapy for Helicobacter pylori infection are declining. Recent studies, conducted in a number of countries, have shown that sequential therapy for H. pylori infection yields high cure rates.

Aim

To compare the efficacy and tolerability of a sequential regimen as a first-line treatment of H. pylori infection with a standard triple treatment regime in Morocco.

Methods

A total of 281 naive H. pylori-infected patients, confirmed by histological examination, were assigned randomly to one of two treatment groups: standard triple therapy [omeprazole (20 mg bid) + amoxicillin (1 g bid) + clarithromycin (500 mg bid) for 7 days] or sequential therapy [omeprazole (20 mg bid) + amoxicillin (1 g bid) for 5 days, followed by omeprazole (20 mg bid) + tinidazole (500 mg bid) + clarithromycin (500 mg bid) for an additional 5 days]. H. pylori eradication was checked 4–6 weeks after treatment initiation by using a 13C-urea breath test. Compliance and adverse events were assessed.

Results

The two groups did not differ significantly in gender, age, previous disease history, endoscopic and histological features and smoking. The intention-to-treat and per-protocol eradication rates were 65.9 and 71 % in the standard triple therapy group, and 82.8 and 89.9 % in the sequential therapy group, respectively. The eradication rate was significantly higher in the sequential therapy group than in the standard triple therapy group (p < 0.001), There was no statistically significant difference in compliance (97.5  vs. 96.3 %) and incidence of side-effects (27.5 vs. 27.9 %) between the two groups.

Conclusions

Based on our results, we conclude that for eradication of H. pylori infection, the 10-day sequential therapy is more effective than the standard triple therapy and is equally tolerated. These results confirm those of other studies in other countries.

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References

  1. Graham DY, Lu H, Yamaoka Y (2007) A report card to grade Helicobacter pylori therapy. Helicobacter 12:275–278

    Article  PubMed  Google Scholar 

  2. Malfertheiner P, Megraud F, O’Morain C et al (1997) Current European concepts in the management of Helicobacter pylori infection–the Maastricht consensus report. The European Helicobacter pylori study group (EHPSG). Eur J Gastroenterol Hepatol 9:1–2

    Article  PubMed  CAS  Google Scholar 

  3. Sasaki M, Ogasawara N, Utsumi K et al (2010) Changes in 12-year first-line eradication rate of Helicobacter pylori based on triple therapy with proton pump inhibitor, amoxicillin and clarithromycin. J Clin Biochem Nutr 47:53–58

    Article  PubMed  CAS  Google Scholar 

  4. Laurent J, Megraud F, Flejou JF et al (2001) A randomized comparison of four omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 15:1787–1793

    Article  PubMed  CAS  Google Scholar 

  5. Iacopini F, Crispino P, Paoluzi OA et al (2005) One-week once-daily triple therapy with esomeprazole, levofloxacin and azithromycin compared to a standard therapy for Helicobacter pylori eradication. Dig Liver Dis 37:571–576

    Article  PubMed  CAS  Google Scholar 

  6. Laheij RJ, Rossum LG, Jansen JB et al (1999) Evaluation of treatment regimens to cure Helicobacter pylori infection—a meta-analysis. Aliment Pharmacol Ther 13:857–864

    Article  PubMed  CAS  Google Scholar 

  7. Malfertheiner P, Megraud F, O’Morain C et al (2007) Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007(56):772–781

    Article  Google Scholar 

  8. Megraud F (2007) Helicobacter pylori and antibiotic resistance. Gut 56(11):1502

    Article  PubMed  Google Scholar 

  9. Gisbert JP, Calvet X, O’Connor A et al (2010) Sequential therapy for Helicobacter pylori eradication: a critical review. J Clin Gastroenterol 44:313–325

    Article  PubMed  CAS  Google Scholar 

  10. Vaira D, Zullo A, Vakil N et al (2007) Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med 146:556–563

    Article  PubMed  Google Scholar 

  11. Zullo A, Rinaldi V, Winn S et al (2000) A new highly effective short-term therapy schedule forHelicobacter pylori eradication. Aliment Pharmacol Ther 14:715–718

    Article  PubMed  CAS  Google Scholar 

  12. Sánchez-Delgado J, Calvet X, Bujanda L et al (2008) Ten-day sequential treatment for Helicobacter pylori eradication in clinical practice. Am J Gastroenterol 103(9):2220–2223

    Article  PubMed  Google Scholar 

  13. Sirimontaporn N, Thong-Ngam D, Tumwasorn S et al (2010) Ten-day sequential therapy of Helicobacter pylori infection in Thailand. Am J Gastroenterol 105(5):1071–1075

    Article  PubMed  Google Scholar 

  14. Kwon JH, Lee DH, Song BJ et al (2010) Ten-day sequential therapy as first-line treatment for Helicobacter pylori infection in Korea: a retrospective study. Helicobacter 15(2):148–153

    Article  PubMed  CAS  Google Scholar 

  15. Jafri NS, Hornung CA, Howden CW (2008) Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med 148:923–931

    Article  PubMed  Google Scholar 

  16. Malfertheiner P, Megraud F, O’Morain CA et al (2012) European Helicobacter Study Group. Management of Helicobacter pylori infection. The Maastricht IV/Florence Consensus Report. Gut 61(5):646–664

    Article  PubMed  CAS  Google Scholar 

  17. Dixon MF, Genta RM, Yardley JH et al (1996) Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston, 1994. Am J Surg Pathol 20:1161–1181

    Article  PubMed  CAS  Google Scholar 

  18. Nishizawa T, Suzuki H, Suzuki M et al (2012) Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor-amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy. J Clin Nutr Biochem 51(2):114–116

    Article  CAS  Google Scholar 

  19. Oh HS, Lee DH, Seo JY et al (2012) Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study. J Gastroenterol Hepatol 27(3):504–509

    Article  PubMed  CAS  Google Scholar 

  20. Basu PP, Rayapudi K, Pacana T et al (2011) Randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol 106(11):1970–1975

    Article  PubMed  CAS  Google Scholar 

  21. Bigard MA, Delchier JC, Riachi G et al (1998) One-week triple therapy using omeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia: influence of dosage of omeprazole and clarithromycin. Aliment Pharmacol Ther 12:383–388

    Article  PubMed  CAS  Google Scholar 

  22. Perri F, Villani MR, Festa V et al (2001) Predictors of failure of Helicobacter pylori eradication with the standard ‘Maastricht triple therapy’. Aliment Pharmacol Ther 15:1023–1029

    Article  PubMed  CAS  Google Scholar 

  23. Kadayifci A, Buyukhatipoglu H, Cemil Savas M et al (2006) Eradication of Helicobacter pylori with triple therapy: an epidemiologic analysis of trends in Turkey over 10 years. Clin Ther 28:1960–1966

    Article  PubMed  CAS  Google Scholar 

  24. Vakil N, Lanza F, Schwartz H et al (2004) Seven-day therapy for Helicobacter pyloriin the United States. Aliment Pharmacol Ther 20:99–107

    Article  PubMed  CAS  Google Scholar 

  25. Graham DY, Fischbach L (2010) Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59:1143–1153

    Article  PubMed  CAS  Google Scholar 

  26. Zullo A, Vaira D, Vakil N et al (2003) High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther 17:719–726

    Article  PubMed  CAS  Google Scholar 

  27. Zullo A, De Francesco V, Hassan C et al (2007) The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut 56:1353–1357

    Article  PubMed  CAS  Google Scholar 

  28. Nadir I, Yonem O, Ozin Y et al (2011) Comparison of two different treatment protocols in Helicobacter pylori eradication. South Med J 104:102–105

    Article  PubMed  Google Scholar 

  29. Glupczynski Y, Megraud F, Lopez-Brea M et al (2001) European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis 20:820–823

    Article  PubMed  CAS  Google Scholar 

  30. Megraud F, Coenen S, Versporten A et al (2013) Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 62:34–42

    Article  PubMed  CAS  Google Scholar 

  31. Kim JM, Kim JS, Jung HC et al (2004) Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agents Chemother 48:4843–4847

    Article  PubMed  CAS  Google Scholar 

  32. Bang SY, Han DS, Eun CS et al (2007) Changing patterns of antibiotic resistance of Helicobacter pylori in patients with peptic ulcer disease. Korean J Gastroenterol 50:356–362

    PubMed  Google Scholar 

  33. De Francesco V, Giorgio F, Hassan C et al (2010) Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointest Liver Dis 19(4):409–414

    Google Scholar 

  34. Alaoui S, Mahmoud M, Amarti A et al. Clarithromycin resistance of Helicobacter pylori: prospective study among patients in the northern center of Morocco. Abstract available at:http://www.snfge.asso.fr/01-Bibliotheque/0A-Resumes-JFHOD/2012/6511.html. Accessed 5 Sept 2012

  35. Uygun A, Kadayifci A, Safali M et al (2007) The efficacy of bismuth containing quadruple therapy as a first-line treatment option for Helicobacter pylori. J Dig Dis 8(4):211–215

    Article  PubMed  CAS  Google Scholar 

  36. Ma J, Liu W, Zhang L et al (2010) A placebo-controlled trial of 10-day bismuth-based quadruple therapy to eradicate Helicobacter pylori infection; a pilot study for the large Linqu County trial. Eur J Gastroenterol Hepatol 22(5):597–601

    Article  PubMed  CAS  Google Scholar 

  37. Salazar CO, Cardenas VM, Reddy RK et al (2012) Greater than 95% success with 14-day Bismuth Quadruple anti-Helicobacter pylori therapy: a pilot study in US Hispanics. Helicobacter 17(5):382–389

    Article  PubMed  CAS  Google Scholar 

  38. Malfertheiner P, Bazzoli F, Delchier JC et al (2011) Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazoleand tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet 377:905–913

    Article  PubMed  CAS  Google Scholar 

  39. Yanai A, Sakamoto K, Akanuma M et al (2012) Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication: a randomized study in Japan. World J Gastrointest Pharmacol Ther 3(1):1–6

    Article  PubMed  Google Scholar 

  40. Essa AS, Kramer JR, Graham DY et al (2009) Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing “concomitant therapy” versus triple therapy for Helicobacter pylori eradication. Helicobacter 14:109–118

    Article  PubMed  CAS  Google Scholar 

  41. Gisbert JP, Calvet X (2011) Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther 34:604–617

    Article  PubMed  CAS  Google Scholar 

  42. Molina-Infante J, Perez-Gallardo B, Fernandez-Bermejo M et al (2010) Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication. Aliment Pharmacol Ther 31(10):1077–1084

    PubMed  CAS  Google Scholar 

  43. Gisbert JP, Morena F (2006) Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 23:35–44

    Article  PubMed  CAS  Google Scholar 

  44. Graham DY, Shiotani A (2008) New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol 5:321–331

    Article  PubMed  CAS  Google Scholar 

  45. Li Y, Huang X, Yao L et al (2010) Advantages of moxifloxacin and levofloxacin-based triple therapy for second-line treatments of persistent Helicobacter pylori infection: a meta analysis. Wien Klin Wochenschr 122:413–422

    Article  PubMed  CAS  Google Scholar 

  46. De Francesco V, Zullo A, Hassan C et al (2001) Two new treatment regimens for Helicobacter pylori eradication: a randomised study. Dig Liver Dis 33:676–679

    Article  PubMed  Google Scholar 

  47. Hassan C, De Francesco V, Zullo A et al (2003) Sequential treatment for Helicobacter pylori eradication in duodenal ulcer patients: improving the cost of pharmacotherapy. Aliment Pharmacol Ther 18:641–646

    Article  PubMed  CAS  Google Scholar 

  48. Paoluzi OA, Visconti E, Andrei F et al (2010) Ten and eight-day sequential therapy in comparison to standard triple therapy for eradicating Helicobacter pylori infection: a randomized controlled study on efficacy and tolerability. J Clin Gastroenterol 44(4):261–266

    Article  PubMed  CAS  Google Scholar 

  49. Sirimontaporn N, Thong-Ngam D, Tumwasorn S et al (2010) Ten-day sequential therapy of Helicobacter pylori infection in Thailand. Am J Gastroenterol 105:1071–1075

    Article  PubMed  Google Scholar 

  50. Park HG, Jung MK, Jung JT et al (2012) Randomised clinical trial: a comparative study of 10-day sequential therapy with 7-day standardtriple therapy for Helicobacter pylori infection in naïve patients. Aliment Pharmacol Ther 35(1):56–65

    Article  PubMed  CAS  Google Scholar 

  51. Zhou YQ, Xu L, Wang BF et al. (2012) Modified sequential therapy. Regimen versus conventional triple therapy for Helicobacter pylori eradication in duodenal ulcer patients in China: a multicenter clinical comparative study. Gastroenterol Res Pract:405425. Epub 2011 Nov 21. doi:10.1155/2012/405425

  52. Gasparetto M, Pescarin M, Guariso G (2012) Helicobacter pylori eradication therapy: current availabilities. ISRN Gastroenterol:186734. Epub 2012 Jul 29. doi:10.5402/2012/186734

  53. Tong JL, Ran ZH, Shen J et al (2009) Sequential therapy vs. standard triple therapies for Helicobacter pylori infection: a meta-analysis. J Clin Pharm Ther 34:41–53

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Samir Ahid.

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Hassan Seddik and Samir Ahid contributed equally to this study

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Seddik, H., Ahid, S., El Adioui, T. et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a prospective randomized study. Eur J Clin Pharmacol 69, 1709–1715 (2013). https://doi.org/10.1007/s00228-013-1524-6

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  • DOI: https://doi.org/10.1007/s00228-013-1524-6

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