Clinical Trials Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2024; 30(6): 556-564
Published online Feb 14, 2024. doi: 10.3748/wjg.v30.i6.556
Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial
Hassan Seddik, Jihane Benass, Sanaa Berrag, Asmae Sair, Reda Berraida, Hanae Boutallaka
Hassan Seddik, Jihane Benass, Asmae Sair, Reda Berraida, Hanae Boutallaka, Department of Gastroenterology II, Mohammed V Military Teaching Hospital of Rabat, Rabat 10100, Morocco
Hassan Seddik, Jihane Benass, Sanaa Berrag, Asmae Sair, Reda Berraida, Hanae Boutallaka, Department of Gastroenterology, Mohammed V University in Rabat, Rabat 10100, Morocco
Sanaa Berrag, Department of Gastroenterology I, Mohammed V Military Teaching Hospital of Rabat, Rabat 10100, Morocco
Author contributions: Seddik H was responsible for study concept and planning and supervised the statistical analysis and manuscript revision; Benass J and Boutallaka H were involved in performing the statistical analysis and writing the manuscript, with input from all authors; Berrag S, Sair A, and Berraida R were involved in patient enrollment and data collection and were involved in manuscript preparation; All authors reviewed the manuscript.
Institutional review board statement: An Institutional Review Board (Scientific committee at Mohammed V Military Teaching Hospital of Rabat) reviewed and approved the trial protocol. Our study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.
Clinical trial registration statement: Our clinical trial has been retrospectively registered in the Pan African Clinical Trial Registry ( on December 7, 2021, Registration No.: PACTR202112632957229.
Informed consent statement: All patients included in the study provided written informed consent before being enrolled in the trial.
Conflict-of-interest statement: The authors report having no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated and/or analyzed during the study are available from the corresponding author on reasonable request.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Jihane Benass, MD, Senior Resident, Department of Gastroenterology II, Mohammed V Military Teaching Hospital of Rabat, Avenue des Forces Armées Royales, Rabat 10100, Morocco.
Received: October 6, 2023
Peer-review started: October 6, 2023
First decision: November 12, 2023
Revised: November 26, 2023
Accepted: December 29, 2023
Article in press: December 29, 2023
Published online: February 14, 2024

A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules.


To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost.


This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test.


In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups.


The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Keywords: Helicobacter pylori, Quadruple therapy, Sequential, Proton-pump inhibitor, Optimization

Core Tip:Helicobacter pylori infection remains a common infection worldwide. The decline in the efficacy of traditional triple therapies since 2010 has required new combinations of antibiotics. The last guidelines of Maastricht VI recommend bismuth quadruple therapies or concomitant quadruple therapies to reach an eradication rate of at least 90%. These values remain higher than those obtained with standard sequential therapy but are associated with a higher cost and more adverse effects (AEs). The results of the present study demonstrate that optimizing sequential therapy by using second-generation proton-pump inhibitors improved eradication rates and reduced AE incidence. This combination can thus be suggested for use in clinical practice.