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

December 27, 2012 updated by: Infante, Javier Molina, M.D.

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Napoli, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria
        • Contact:
        • Principal Investigator:
          • Marco Romano
        • Sub-Investigator:
          • Antonio Cuomo
        • Sub-Investigator:
          • Riccardo Marmo
        • Sub-Investigator:
          • Gerardo Nardone
        • Sub-Investigator:
          • Roberto Lamanda
  • Spain
      • Caceres, Spain, 10003
        • Recruiting
        • Hospital San Pedro de Alcantara
        • Contact:
        • Principal Investigator:
          • Javier Molina-Infante, MD
        • Sub-Investigator:
          • Belen Perez-Gallardo, MD
        • Sub-Investigator:
          • Miguel Fernandez-Bermejo, MD
    • Badajoz
      • Merida, Badajoz, Spain
        • Recruiting
        • Hospital de Mérida
        • Contact:
        • Principal Investigator:
          • Liliana Pozzati, MD
        • Sub-Investigator:
          • Marta Gata-Cuadrado
    • Caceres
      • Plasencia, Caceres, Spain
        • Recruiting
        • Hospital Virgen Del Puerto
        • Contact:
        • Principal Investigator:
          • Elena G Abadia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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
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
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
Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
"Intention to treat" eradication rates
Time Frame: 1 year
"Intention-to-treat" eradication of infection.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
" Per protocol" eradication rate
Time Frame: 1 year
" Per protocol" eradication of the infection
1 year
Treatment compliance
Time Frame: 1 year
1 year
Number of participants with adverse events
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Infante, Javier Molina, M.D.

Investigators

  • Principal Investigator: Javier Molina-Infante, MD, Hospital San Pedro de Alcantara, Caceres, Spain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Anticipated)

December 1, 2012

Study Completion (Anticipated)

January 1, 2013

Study Registration Dates

First Submitted

October 25, 2011

First Submitted That Met QC Criteria

October 31, 2011

First Posted (Estimate)

November 3, 2011

Study Record Updates

Last Update Posted (Estimate)

December 31, 2012

Last Update Submitted That Met QC Criteria

December 27, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INHIBRICON14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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