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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Infante, Javier Molina, M.D.
Sponsor:
Information provided by (Responsible Party):
Infante, Javier Molina, M.D.
ClinicalTrials.gov Identifier:
NCT01464060
First received: October 25, 2011
Last updated: December 27, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Helicobacter Pylori Infection
Drug: PPI, amoxicillin, metronidazole and clarithromycin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 4, Prospective, Randomized Study Comparing 14-day Non-bismuth Quadruple "Hybrid" and "Concomitant" Therapies for Helicobacter Pylori Eradication in Settings With High Clarithromycin Resistance

Resource links provided by NLM:


Further study details as provided by Infante, Javier Molina, M.D.:

Primary Outcome Measures:
  • "Intention to treat" eradication rates [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    "Intention-to-treat" eradication of infection.


Secondary Outcome Measures:
  • " Per protocol" eradication rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    " Per protocol" eradication of the infection

  • Treatment compliance [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 400
Study Start Date: September 2011
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: "Hybrid" therapy
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
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.
Experimental: "Concomitant" therapy
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
Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h

Detailed Description:

Justification of the study:

Several non-bismuth quadruple clarithromycin-containing regimens have raised over the last decade aiming to substitute standard triple therapy (STT) for first-line H. pylori eradication therapy. Sequential therapy, introduced in Italy, 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. 10-day sequential therapy proved more effectiveness than STT with excellent treatment compliance and minimal side effects. However, the efficacy of sequential therapy seems to be notably impaired by clarithromycin resistance and dual clarithromycin and metronidazole resistance, which is becoming a common scenario in developed countries.

Other interesting and resurfaced therapeutic alternative is the non-bismuth quadruple therapy (NBQT), also called "concomitant" therapy, which includes a PPI, amoxicillin, clarithromycin and a nitroimidazole, all drugs given concurrently and twice daily. It has also demonstrated its superiority over STT and it could be potential replacement for STT as first-line regimen. However, NBQT might have several advantages over sequential therapy, namely, less complexity for both the patient and the physician, twice the duration of all prescribed antibiotics, a proper validation process worldwide and a higher efficacy over sequential therapy for both clarithromycin and dual-resistant H. pylori. Finally, another recent innovation is the 14-day quadruple clarithromycin-based regimen, so-called the sequential-concomitant "hybrid" therapy, which involves PPI and amoxicillin for 7 days plus a 7-day course of NBQT. Outstanding cure rates close to 100% have been recently reported using this scheme, thereby requiring further consideration.

Therefore it is necessary to make a controlled clinical trial to directly compare NBQT "hybrid" versus "concomitant" therapy in settings with documented high clarithromycin resistance rates. In order to maximize the efficacy of eradication regimens, it would be necessary to extend duration to 14 days and using high-dose PPI (omeprazole 40 mg bid). The results of this study will conclude whether there is still room for clarithromycin-containing regimens in H. pylori eradication even in settings with high antibiotic resistance rates.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01464060

Contacts
Contact: Javier Molina-Infante, MD 0034627430248 xavi_molina@hotmail.com

Locations
Italy
Azienda Ospedaliera Universitaria Recruiting
Napoli, Italy
Contact: Marco Romano, MD,PhD       marco.romano@unina2.it   
Principal Investigator: Marco Romano         
Sub-Investigator: Antonio Cuomo         
Sub-Investigator: Riccardo Marmo         
Sub-Investigator: Gerardo Nardone         
Sub-Investigator: Roberto Lamanda         
Spain
Hospital de Merida Recruiting
Merida, Badajoz, Spain
Contact: Liliana Pozzati, MD       santelmo0054@hotmail.com   
Principal Investigator: Liliana Pozzati, MD         
Sub-Investigator: Marta Gata-Cuadrado         
Hospital Virgen del Puerto Recruiting
Plasencia, Caceres, Spain
Contact: Elena G Abadia       elenagabadia@hotmail.com   
Principal Investigator: Elena G Abadia         
Hospital San Pedro de Alcantara Recruiting
Caceres, Spain, 10003
Contact: Javier Molina-Infante, MD       xavi_molina@hotmail.com   
Principal Investigator: Javier Molina-Infante, MD         
Sub-Investigator: Belen Perez-Gallardo, MD         
Sub-Investigator: Miguel Fernandez-Bermejo, MD         
Sponsors and Collaborators
Infante, Javier Molina, M.D.
Investigators
Principal Investigator: Javier Molina-Infante, MD Hospital San Pedro de Alcantara, Caceres, Spain
  More Information

Publications:
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Infante, Javier Molina, M.D.
ClinicalTrials.gov Identifier: NCT01464060     History of Changes
Other Study ID Numbers: INHIBRICON14
Study First Received: October 25, 2011
Last Updated: December 27, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Infante, Javier Molina, M.D.:
Helicobacter pylori
Quadruple therapy
Clarithromycin resistance

Additional relevant MeSH terms:
Helicobacter Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Amoxicillin
Clarithromycin
Metronidazole
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiprotozoal Agents
Antiparasitic Agents
Radiation-Sensitizing Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2014