Study Comparing Sequential and Concomitant Therapy for Helicobacter Pylori Eradication in Routine Clinical Practice
Summary
Helicobacter pylori is the main cause of chronic gastritis, peptic ulcer and gastric tumors (adenocarcinoma and lymphoma). The cure of the H. pylori infection prevents recurrence of duodenal and gastric ulcer and improves dyspepsia in a significant proportion of cases, so it is cost-effective. Eradication therapy has changed over time. The usually recommended pattern in the consensus conferences has traditionally been triple therapy, composed by the combination of 2 antibiotics (clarithromycin plus amoxicillin or metronidazole) and a proton pump inhibitor (PPI) for 7-14 days. Recent meta-analyses have that the current global eradication rate after standard triple therapy is less than 80%. Several European studies have found even lower eradication rates, with 35-40% of cases resulting in treatment failure. Treatment failure leads to a second treatment and a new diagnostic test to confirm eradication.
Timeline
- Start
- 2010-12
- Primary completion
- 2012-06
- Completion
- 2012-07
Publications
- Background Forbes GM, Glaser ME, Cullen DJ, Warren JR, Christiansen KJ, Marshall BJ, Collins BJ. Duodenal ulcer treated with Helicobacter pylori eradication: seven-year follow-up. Lancet. 1994 Jan 29;343(8892):258-60. doi: 10.1016/s0140-6736(94)91111-8.
- Background Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol. 1998 Dec;93(12):2330-8. doi: 10.1111/j.1572-0241.1998.00684.x. No abstract available.
- Background Laheij RJ, Rossum LG, Jansen JB, Straatman H, Verbeek AL. Evaluation of treatment regimens to cure Helicobacter pylori infection--a meta-analysis. Aliment Pharmacol Ther. 1999 Jul;13(7):857-64. doi: 10.1046/j.1365-2036.1999.00542.x.
- Background Calvet X, Ducons J, Bujanda L, Bory F, Montserrat A, Gisbert JP; Hp Study Group of the Asociacion Espanola de Gastroenterologia. Seven versus ten days of rabeprazole triple therapy for Helicobacter pylori eradication: a multicenter randomized trial. Am J Gastroenterol. 2005 Aug;100(8):1696-701. doi: 10.1111/j.1572-0241.2005.50019.x.
- Background Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. 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. 2000 May;14(5):603-9. doi: 10.1046/j.1365-2036.2000.00744.x.
- Background Gene E, Calvet X, Azagra R, Gisbert JP. Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis. Aliment Pharmacol Ther. 2003 May 1;17(9):1137-43. doi: 10.1046/j.1365-2036.2003.01566.x.
- Background Zullo A, Rinaldi V, Winn S, Meddi P, Lionetti R, Hassan C, Ripani C, Tomaselli G, Attili AF. A new highly effective short-term therapy schedule for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000 Jun;14(6):715-8. doi: 10.1046/j.1365-2036.2000.00766.x.
- Background Zullo A, Vaira D, Vakil N, Hassan C, Gatta L, Ricci C, De Francesco V, Menegatti M, Tampieri A, Perna F, Rinaldi V, Perri F, Papadia C, Fornari F, Pilati S, Mete LS, Merla A, Poti R, Marinone G, Savioli A, Campo SM, Faleo D, Ierardi E, Miglioli M, Morini S. High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther. 2003 Mar 1;17(5):719-26. doi: 10.1046/j.1365-2036.2003.01461.x.
- Background Zullo A, Gatta L, De Francesco V, Hassan C, Ricci C, Bernabucci V, Cavina M, Ierardi E, Morini S, Vaira D. High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther. 2005 Jun 15;21(12):1419-24. doi: 10.1111/j.1365-2036.2005.02519.x.
- Background Francavilla R, Lionetti E, Castellaneta SP, Magista AM, Boscarelli G, Piscitelli D, Amoruso A, Di Leo A, Miniello VL, Francavilla A, Cavallo L, Ierardi E. Improved efficacy of 10-Day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology. 2005 Nov;129(5):1414-9. doi: 10.1053/j.gastro.2005.09.007.
- Background Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol. 2006 Feb;20(2):113-7. doi: 10.1155/2006/258768.
- Background De Francesco V, Zullo A, Margiotta M, Marangi S, Burattini O, Berloco P, Russo F, Barone M, Di Leo A, Minenna MF, Stoppino V, Morini S, Panella C, Francavilla A, Ierardi E. Sequential treatment for Helicobacter pylori does not share the risk factors of triple therapy failure. Aliment Pharmacol Ther. 2004 Feb 15;19(4):407-14. doi: 10.1046/j.1365-2036.2004.01818.x.
- Background Vaira D, Zullo A, Vakil N, Gatta L, Ricci C, Perna F, Hassan C, Bernabucci V, Tampieri A, Morini S. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007 Apr 17;146(8):556-63. doi: 10.7326/0003-4819-146-8-200704170-00006.
- Background De Francesco V, Zullo A, Hassan C, Faleo D, Ierardi E, Panella C, Morini S. Two new treatment regimens for Helicobacter pylori eradication: a randomised study. Dig Liver Dis. 2001 Nov;33(8):676-9. doi: 10.1016/s1590-8658(01)80044-x.
- Background Zullo A, De Francesco V, Hassan C, Morini S, Vaira D. The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut. 2007 Oct;56(10):1353-7. doi: 10.1136/gut.2007.125658. Epub 2007 Jun 12.
- Background Sanchez-Delgado J, Calvet X, Bujanda L, Gisbert JP, Tito L, Castro M. Ten-day sequential treatment for Helicobacter pylori eradication in clinical practice. Am J Gastroenterol. 2008 Sep;103(9):2220-3. doi: 10.1111/j.1572-0241.2008.01924.x. Epub 2008 Jun 28.
- Background Unge P. Review of Helicobacter pylori eradication regimens. Scand J Gastroenterol Suppl. 1996;215:74-81.
- Background Sykora J, Siala K, Varvarovska J, Pazdiora P, Pomahacova R, Huml M. Epidemiology of Helicobacter pylori infection in asymptomatic children: a prospective population-based study from the Czech Republic. Application of a monoclonal-based antigen-in-stool enzyme immunoassay. Helicobacter. 2009 Aug;14(4):286-97. doi: 10.1111/j.1523-5378.2009.00689.x.
- Background Vakil N. H. pylori treatment: new wine in old bottles? Am J Gastroenterol. 2009 Jan;104(1):26-30. doi: 10.1038/ajg.2008.91.
- Background Graham DY, Lu H, Yamaoka Y. Therapy for Helicobacter pylori infection can be improved: sequential therapy and beyond. Drugs. 2008;68(6):725-36. doi: 10.2165/00003495-200868060-00001.
- Background Graham DY, Lu H. Is there a role for sequential in sequential anti-H. pylori therapy? Gastroenterology. 2006 May;130(6):1930-1; author reply 1931. doi: 10.1053/j.gastro.2006.03.037. No abstract available.
- Background Calvet X, Tito L, Comet R, Garcia N, Campo R, Brullet E. Four-day, twice daily, quadruple therapy with amoxicillin, clarithromycin, tinidazole and omeprazole to cure Helicobacter pylori infection: a pilot study. Helicobacter. 2000 Mar;5(1):52-6. doi: 10.1046/j.1523-5378.2000.00007.x.
- Background Catalano F, Branciforte G, Catanzaro R, Cipolla R, Bentivegna C, Brogna A. Helicobacter pylori-positive duodenal ulcer: three-day antibiotic eradication regimen. Aliment Pharmacol Ther. 2000 Oct;14(10):1329-34. doi: 10.1046/j.1365-2036.2000.00839.x.
- Background Gisbert JP, Marcos S, Gisbert JL, Pajares JM. High efficacy of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for only five days in Helicobacter pylori Eradication. Helicobacter. 2001 Jun;6(2):157-62. doi: 10.1046/j.1523-5378.2001.00023.x.
- Background Nagahara A, Miwa H, Ogawa K, Kurosawa A, Ohkura R, Iida N, Sato N. Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an excellent cure rate with five-day therapy. Helicobacter. 2000 Jun;5(2):88-93. doi: 10.1046/j.1523-5378.2000.00013.x.
- Background Nagahara A, Miwa H, Yamada T, Kurosawa A, Ohkura R, Sato N. Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection. Aliment Pharmacol Ther. 2001 Mar;15(3):417-21. doi: 10.1046/j.1365-2036.2001.00929.x.
- Background Neville PM, Everett S, Langworthy H, Tompkins D, Mapstone NP, Axon AT, Moayyedi P. The optimal antibiotic combination in a 5-day Helicobacter pylori eradication regimen. Aliment Pharmacol Ther. 1999 Apr;13(4):497-501. doi: 10.1046/j.1365-2036.1999.00493.x.
- Background Okada M, Oki K, Shirotani T, Seo M, Okabe N, Maeda K, Nishimura H, Ohkuma K, Oda K. A new quadruple therapy for the eradication of Helicobacter pylori. Effect of pretreatment with omeprazole on the cure rate. J Gastroenterol. 1998 Oct;33(5):640-5. doi: 10.1007/s005350050150.
- Background Okada M, Nishimura H, Kawashima M, Okabe N, Maeda K, Seo M, Ohkuma K, Takata T. A new quadruple therapy for Helicobacter pylori: influence of resistant strains on treatment outcome. Aliment Pharmacol Ther. 1999 Jun;13(6):769-74. doi: 10.1046/j.1365-2036.1999.00551.x.
- Background Treiber G, Ammon S, Schneider E, Klotz U. Amoxicillin/metronidazole/omeprazole/clarithromycin: a new, short quadruple therapy for Helicobacter pylori eradication. Helicobacter. 1998 Mar;3(1):54-8. doi: 10.1046/j.1523-5378.1998.08019.x.
- Background Treiber G, Wittig J, Ammon S, Walker S, van Doorn LJ, Klotz U. Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med. 2002 Jan 28;162(2):153-60. doi: 10.1001/archinte.162.2.153.
- Background Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing "concomitant therapy" versus triple therapy for Helicobacter pylori eradication. Helicobacter. 2009 Apr;14(2):109-18. doi: 10.1111/j.1523-5378.2009.00671.x.
- Background Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SS, Chen A, Hung WC, Graham DY. Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol. 2010 Jan;8(1):36-41.e1. doi: 10.1016/j.cgh.2009.09.030. Epub 2009 Oct 3.
- McNicholl AG, Marin AC, Molina-Infante J, Castro M, Barrio J, Ducons J, Calvet X, de la Coba C, Montoro M, Bory F, Perez-Aisa A, Forne M, Gisbert JP; Participant Centres. Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice. Gut. 2014 Feb;63(2):244-9. doi: 10.1136/gutjnl-2013-304820. Epub 2013 May 11.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Amoxicillin | Other / unclassified | 1 g | — |
| Subject | Clarithromycin | Small molecule | 500 mg | — |
| Subject | Metronidazole | Small molecule | 500 mg | — |
| Subject | Omeprazole | Other / unclassified | 20 mg | — |