14-day Quadruple Hybrid vs. Concomitant Therapies for Helicobacter Pylori Eradication
Information source: Infante, Javier Molina, M.D.
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Helicobacter Pylori Infection
Intervention: PPI, amoxicillin, metronidazole and clarithromycin (Drug); PPI, amoxicillin, metronidazole and clarithromycin (Drug)
Phase: Phase 4
Sponsored by: Infante, Javier Molina, M.D.
Official(s) and/or principal investigator(s):
Javier Molina-Infante, MD, Principal Investigator, Affiliation: Hospital San Pedro de Alcantara, Caceres, Spain
Javier Molina-Infante, MD, Phone: 0034627430248, Email: firstname.lastname@example.org
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.
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: "Intention to treat" eradication rates
" Per protocol" eradication rate
Number of participants with adverse events
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.
Minimum age: 18 Years.
Maximum age: N/A.
- Patients with dyspepsia or peptic gastroduodenal ulcer for whom eradication treatment
- 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
- Age less than 18 years.
- Advanced chronic disease or any other pathology that prevents attending controls and
- 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
Locations and Contacts
Javier Molina-Infante, MD, Phone: 0034627430248, Email: email@example.com
Azienda Ospedaliera Universitaria, Napoli, Italy; Recruiting
Marco Romano, MD,PhD, Email: firstname.lastname@example.org
Marco Romano, Principal Investigator
Antonio Cuomo, Sub-Investigator
Riccardo Marmo, Sub-Investigator
Gerardo Nardone, Sub-Investigator
Roberto Lamanda, Sub-Investigator
Hospital San Pedro de Alcantara, Caceres 10003, Spain; Recruiting
Javier Molina-Infante, MD, Email: email@example.com
Javier Molina-Infante, MD, Principal Investigator
Belen Perez-Gallardo, MD, Sub-Investigator
Miguel Fernandez-Bermejo, MD, Sub-Investigator
Hospital de Merida, Merida, Badajoz, Spain; Recruiting
Liliana Pozzati, MD, Email: firstname.lastname@example.org
Liliana Pozzati, MD, Principal Investigator
Marta Gata-Cuadrado, Sub-Investigator
Hospital Virgen del Puerto, Plasencia, Caceres, Spain; Recruiting
Elena G Abadia, Email: email@example.com
Elena G Abadia, Principal Investigator
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Starting date: September 2011
Last updated: December 27, 2012