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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
"Intention to treat" eradication rates
"Intention-to-treat" eradication of infection.
Javier Molina-Infante, MD
Hospital San Pedro de Alcantara, Caceres, Spain
Spain: Agencia Española de Medicamentos y Productos Sanitarios