Study Comparing Sequential and Concomitant Therapy for Helicobacter Pylori Eradication in Routine Clinical Practice
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Justification of the study:
One of the latest therapeutic innovations is sequential therapy, introduced in Italy by Zullo et al. The drug delivery strategy involves a 5-day induction phase with dual therapy (a PPI every 12 hours and amoxicillin 1g every 12 hours), followed immediately by triple therapy for 5 days with a PPI every 12 hours, metronidazole 500 mg every 12 hours and clarithromycin 500 mg every 12 hours. Sequential therapy has proved more effectiveness than standard triple therapy for seven and ten days. In order to assess the efficacy of this new treatment in our area, over the past year we conducted a multicentre observational pilot study in routine clinical practice conditions in patients infected with H. pylori and with indications for eradication. 139 patients from 6 different centres were included. Excellent treatment compliance and minimal side effects, similar to those described with triple therapy, were shown. The results confirm similar efficacy to that obtained in previous studies and an eradication rate significantly higher than that obtained with classic triple therapy in our area.
Several previous studies have shown excellent efficacy of quadruple therapy with a PPI, amoxicillin, clarithromycin and metronidazole, administering "concomitantly" the same drugs as those of sequential therapy, but only for 5-7 days. Several studies have found a higher eradication rate of this "concomitant" therapy as compared with classic triple therapy. The results of a randomized study in which sequential and concomitant therapy were compared have recently been reported in the American Congress of Gastroenterology. Eradication and adverse events rates were similar with both treatments. This data suggest that the "sequentially"administration of these drugs probably complicated unnecessarily the treatment.
Therefore it is necessary to make a controlled clinical trial to directly compare "sequential" versus "concomitant" therapy. The results of this study will conclude which should be the first line treatment for H. pylori eradication.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Sequential treatment:
|
Drug: PPI, amoxicillin, metronidazole and clarithromycin
Dual therapy for 5 days: PPI and 1g amoxicillin every 12h. After dual therapy continue with a triple therapy for 5 days: PPI, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.
|
| Experimental: Concomitant treatment
|
Drug: PPI, amoxicillin, metronidazole and clarithromycin
Quadruple therapy for ten days:PPI, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h
|
Outcome Measures
Primary Outcome Measures
- "Intention to treat" eradication rates [One year]
"Intention-to-treat" eradication of infection.
Secondary Outcome Measures
- "Per protocol" Eradication rate [One year]
"Per protocol" eradication of infection.
- Compliance [One year]
Treatment compliance
- Adverse events [One year]
Adverse events
- Clinical and demographic variables [One year]
Age Sex Smoking habits Comorbidity (diabetes mellitus, arterial hypertension, ischemic heart disease, dyslipidemia, others) Indication for eradication (peptic ulcer vs. uninvestigated or functional dyspepsia) Initial diagnostic test for H. pylori infection.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Inclusion of patients with dyspepsia or peptic gastroduodenal ulcer for whom eradication treatment is indicated.
-
Requirement of confirmation of the diagnosis of H. pylori infection by at least one positive test out of the following: breath test, histology, rapid urease test or culture.
Exclusion Criteria:
-
Age less than 18 years.
-
Advanced chronic disease or any other pathology that prevents attending controls and follow up.
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Allergy to any of the antibiotics in the treatment.
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Previous gastric surgery
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Pregnancy and lactation.
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History of alcohol or drug abuse.
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Previous eradication treatment.
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Consumption of antibiotics or bismuth salts during the last 4 weeks
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital del Mar | Barcelona | Spain | ||
| 2 | Hospital San Pedro de Alcántara | Cáceres | Spain | ||
| 3 | Hospital de Cabueñes | Gijón | Spain | ||
| 4 | Hospital San Jorge | Huesca | Spain | ||
| 5 | Hospital Universitario de La Princesa | Madrid | Spain | ||
| 6 | Hospital Costa del Sol | Málaga | Spain | ||
| 7 | Hospital de Sabadell | Sabadell | Spain | ||
| 8 | Hospital Universitario de Valme | Sevilla | Spain | ||
| 9 | Hospital Mútua de Terrassa | Terrassa | Spain | ||
| 10 | Hospital Universitario Río Hortega | Valladolid | Spain | ||
| 11 | Hospital Clínico Universitario "Lozano Blesa" | Zaragoza | Spain |
Sponsors and Collaborators
- Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Investigators
- Principal Investigator: Javier P. Gisbert, Physician Doctor, Digestive Service, Hospital Universitario de La Princesa
Study Documents (Full-Text)
None provided.More Information
Publications
- Calvet X, Ducons J, Bujanda L, Bory F, Montserrat A, Gisbert JP; Hp Study Group of the Asociación Española de Gastroenterología. 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.
- Calvet X, García N, López T, Gisbert JP, Gené 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.
- Calvet X, Titó L, Comet R, García 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Francavilla R, Lionetti E, Castellaneta SP, Magistà 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.
- Gené 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.
- 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.
- Graham DY, Lu H, Yamaoka Y. Therapy for Helicobacter pylori infection can be improved: sequential therapy and beyond. Drugs. 2008;68(6):725-36.
- 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.
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Sánchez-Delgado J, Calvet X, Bujanda L, Gisbert JP, Titó 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.
- 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.
- Sýkora J, Siala K, Varvarovská J, Pazdiora P, Pomahacová 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.
- 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.
- 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.
- Unge P. Review of Helicobacter pylori eradication regimens. Scand J Gastroenterol Suppl. 1996;215:74-81.
- 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.
- 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. Review.
- 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.
- 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. Epub 2007 Jun 12. Review.
- 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.
- 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.
- 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, Papadìa C, Fornari F, Pilati S, Mete LS, Merla A, Potì 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. Erratum in: Aliment Pharmacol Ther. 2003 May 1;17(9):1205.
- SEQvsCONC (TRA-047)