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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

Phase 4
18 Years
Open (Enrolling)
Helicobacter Pylori Infection

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Trial Information

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

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.

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

"Intention to treat" eradication rates

Outcome Description:

"Intention-to-treat" eradication of infection.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Javier Molina-Infante, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hospital San Pedro de Alcantara, Caceres, Spain


Spain: Agencia EspaƱola de Medicamentos y Productos Sanitarios

Study ID:




Start Date:

September 2011

Completion Date:

January 2013

Related Keywords:

  • Helicobacter Pylori Infection
  • Helicobacter pylori
  • Quadruple therapy
  • Clarithromycin resistance
  • Helicobacter Infections