14-day Quadruple Hybrid vs. Concomitant Therapies for Helicobacter Pylori Eradication

NCT01464060 | Unknown Phase 4 DMC

• 1 other identifier: INHIBRICON14
• Study Type: interventional
• Target: 400
• Locations: 2 countries
• Sites: 4

Brief Summary

Helicobacter pylori (H. pylori) infects approximately 50% of the adult population and is well recognized as the main cause of gastritis, peptic ulcer disease and gastric cancer. 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. Recent meta-analyses have that the current global eradication rate after standard triple therapy (STT) is less than 80%. Several European studies have found even lower eradication rates, with 35-40% of cases resulting in treatment failure, probably due to increased resistance to antibiotics in many geographical areas, principally to clarithromycin. The usually recommended pattern in the American and European (Maastricht III) consensus conferences from 2007 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. However, triple therapy was discouraged in settings with high rates of clarithromycin resistance (15-20%) and, as such, new strategies in order to improve the efficacy of first-line treatments are required. Treatment failure increases antibiotic resistant strains, leads to a second treatment and a new diagnostic test to confirm eradication. Unfortunately, it remains unknown whether there is room for improvement in these geographical areas using clarithromycin-containing therapies or switching to bismuth quadruple therapy should be followed instead.

Conditions

Helicobacter Pylori Infection

Keywords

Helicobacter pylori; Quadruple therapy; Clarithromycin resistance

Outcome Measures

Primary Outcomes (1)

• "Intention to treat" eradication rates

  "Intention-to-treat" eradication of infection.

  1 year

Secondary Outcomes (3)

• " Per protocol" eradication rate

  1 year

• Treatment compliance

  1 year

• Number of participants with adverse events

  1 year

Study Arms (2)

"Hybrid" therapy

ACTIVE COMPARATOR

Dual therapy for 7 days: 40 mg omeprazole and 1g amoxicillin every 12h. After dual therapy continue with a quadruple therapy for 7 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.

Drug: PPI, amoxicillin, metronidazole and clarithromycin

"Concomitant" therapy

EXPERIMENTAL

Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h

Drug: PPI, amoxicillin, metronidazole and clarithromycin

Interventions

PPI, amoxicillin, metronidazole and clarithromycin DRUG

Dual therapy for 7 days: 40 mg omeprazole and 1g amoxicillin every 12h. After dual therapy continue with a quadruple therapy for 7 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.

"Hybrid" therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Age less than 18 years.
• Advanced chronic disease or any other pathology that prevents attending controls and follow up.
• Allergy to any of the antibiotics in the treatment.
• Previous gastric surgery
• Pregnancy and lactation.
• History of alcohol or drug abuse.
• Previous eradication treatment.
• Consumption of antibiotics or bismuth salts during the last 4 weeks

Sponsors & Collaborators

• Infante, Javier Molina, M.D.: lead

Study Sites (4)

Azienda Ospedaliera Universitaria

Napoli, Napoli, Italy

RECRUITING

Hospital de Merida

Mérida, Badajoz, Spain

RECRUITING

Hospital San Pedro de Alcantara

Cáceres, Caceres, 10003, Spain

RECRUITING

Hospital Virgen del Puerto

Plasencia, Caceres, Spain

RECRUITING

Related Publications (28)

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  PMID: 17170018 BACKGROUND

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  PMID: 17608775 BACKGROUND

• Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008 Jun;5(6):321-31. doi: 10.1038/ncpgasthep1138. Epub 2008 Apr 29.

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  PMID: 20525969 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.

  PMID: 17566020 BACKGROUND

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• Tong JL, Ran ZH, Shen J, Xiao SD. Sequential therapy vs. standard triple therapies for Helicobacter pylori infection: a meta-analysis. J Clin Pharm Ther. 2009 Feb;34(1):41-53. doi: 10.1111/j.1365-2710.2008.00969.x.

  PMID: 19125902 BACKGROUND

• Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol. 2009 Dec;104(12):3069-79; quiz 1080. doi: 10.1038/ajg.2009.555. Epub 2009 Oct 20.

  PMID: 19844205 BACKGROUND

• Gisbert JP, Calvet X, O'Connor A, Megraud F, O'Morain CA. Sequential therapy for Helicobacter pylori eradication: a critical review. J Clin Gastroenterol. 2010 May-Jun;44(5):313-25. doi: 10.1097/MCG.0b013e3181c8a1a3.

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• Gisbert JP, Nyssen OP, McNicholl A, et al. Meta-analysis of sequential vs. standard triple therapy for Helicobacter pylori eradication. Helicobacter 2011;16 (Suppl 1):131.

  BACKGROUND

• Prieto-Jimenez CA, Cardenas VM, Fischbach LA, Mulla ZD, Rivera JO, Dominguez DC, Graham DY, Ortiz M. Double-blind randomized trial of quadruple sequential Helicobacter pylori eradication therapy in asymptomatic infected children in El Paso, Texas. J Pediatr Gastroenterol Nutr. 2011 Mar;52(3):319-25. doi: 10.1097/MPG.0b013e318206870e.

  PMID: 21336156 BACKGROUND

• Bontems P, Kalach N, Oderda G, Salame A, Muyshont L, Miendje DY, Raymond J, Cadranel S, Scaillon M. Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr. 2011 Dec;53(6):646-50. doi: 10.1097/MPG.0b013e318229c769.

  PMID: 21701406 BACKGROUND

• Molina-Infante J, Perez-Gallardo B, Fernandez-Bermejo M, Hernandez-Alonso M, Vinagre G, Duenas C, Mateos-Rodriguez JM, Gonzalez-Garcia G, Abadia EG, Gisbert JP. Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2010 May;31(10):1077-84. doi: 10.1111/j.1365-2036.2010.04274.x. Epub 2010 Feb 20.

  PMID: 20180787 BACKGROUND

• Choi WH, Park DI, Oh SJ, Baek YH, Hong CH, Hong EJ, Song MJ, Park SK, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI. [Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea]. Korean J Gastroenterol. 2008 May;51(5):280-4. Korean.

  PMID: 18516011 BACKGROUND

• Remes-Troche JM, Alarcon-Rivera G, Ramos-de la Medina A, et al. Sequential therapy vs standard triple therapy as treatment of Helicobacter pylori infection. A prospective, randomized, parallel-group, open-label study in Mexico. Gastroenterology 2010;138:S-336.

  BACKGROUND

• Romano M, Cuomo A, Gravina AG, Miranda A, Iovene MR, Tiso A, Sica M, Rocco A, Salerno R, Marmo R, Federico A, Nardone G. Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial. Gut. 2010 Nov;59(11):1465-70. doi: 10.1136/gut.2010.215350.

  PMID: 20947881 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.

  PMID: 19804842 BACKGROUND

• Sirimontaporn N, Thong-Ngam D, Tumwasorn S, Mahachai V. Ten-day sequential therapy of Helicobacter pylori infection in Thailand. Am J Gastroenterol. 2010 May;105(5):1071-5. doi: 10.1038/ajg.2009.708. Epub 2009 Dec 15.

  PMID: 20010919 BACKGROUND

• Mahachai V, Sirimontaporn N, Tumwasorn S, Thong-Ngam D, Vilaichone RK. Sequential therapy in clarithromycin-sensitive and -resistant Helicobacter pylori based on polymerase chain reaction molecular test. J Gastroenterol Hepatol. 2011 May;26(5):825-8. doi: 10.1111/j.1440-1746.2011.06660.x.

  PMID: 21251064 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.

  PMID: 17438314 BACKGROUND

• Gisbert JP, Calvet X. Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther. 2011 Sep;34(6):604-17. doi: 10.1111/j.1365-2036.2011.04770.x. Epub 2011 Jul 11.

  PMID: 21745241 BACKGROUND

• Molina-Infante J, Pazos-Pacheco MC, Perez-Gallardo B, et al. Efficacy of non-bismuth quadruple "concomitant" therapy for H. pylori infection in a setting with high clarithromycin resistance. Gastroenterology 2011; Suppl 1:S-880.

  BACKGROUND

• Hsu PI, Wu DC, Wu JY, Graham DY. Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days. Helicobacter. 2011 Apr;16(2):139-45. doi: 10.1111/j.1523-5378.2011.00828.x.

  PMID: 21435092 BACKGROUND

• Malfertheiner P, Bazzoli F, Delchier JC, Celinski K, Giguere M, Riviere M, Megraud F; Pylera Study Group. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011 Mar 12;377(9769):905-13. doi: 10.1016/S0140-6736(11)60020-2. Epub 2011 Feb 21.

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• Dore MP, Farina V, Cuccu M, Mameli L, Massarelli G, Graham DY. Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days. Helicobacter. 2011 Aug;16(4):295-300. doi: 10.1111/j.1523-5378.2011.00857.x.

  PMID: 21762269 BACKGROUND

• Villoria A, Garcia P, Calvet X, Gisbert JP, Vergara M. Meta-analysis: high-dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2008 Oct 1;28(7):868-77. doi: 10.1111/j.1365-2036.2008.03807.x. Epub 2008 Jul 17.

  PMID: 18644011 BACKGROUND

• Molina-Infante J, Romano M, Fernandez-Bermejo M, Federico A, Gravina AG, Pozzati L, Garcia-Abadia E, Vinagre-Rodriguez G, Martinez-Alcala C, Hernandez-Alonso M, Miranda A, Iovene MR, Pazos-Pacheco C, Gisbert JP. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology. 2013 Jul;145(1):121-128.e1. doi: 10.1053/j.gastro.2013.03.050. Epub 2013 Apr 3.

  PMID: 23562754 DERIVED

MeSH Terms

Interventions

Amoxicillin; Metronidazole; Clarithromycin

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Erythromycin; Macrolides; Polyketides; Lactones

Study Officials

• Javier Molina-Infante, MD

  Hospital San Pedro de Alcantara, Caceres, Spain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Javier Molina-Infante, MD

CONTACT

0034627430248; xavi_molina@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2011
• First Posted: November 3, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: January 1, 2013
• Last Updated: December 31, 2012

Record last verified: 2012-12

Locations

IT (1); ES (3)