Concomitant, sequential, and hybrid therapy for H. pylori eradication: A pilot study

doi:10.1016/j.clinre.2013.04.003

Clinics and Research in Hepatology and Gastroenterology

Volume 37, Issue 6, December 2013, Pages 647-650

https://doi.org/10.1016/j.clinre.2013.04.003 Get rights and content

Summary

Background and objective

Since the efficacy of the standard triple therapies for Helicobacter pylori eradication has decreased, novel antibiotic regimens have been introduced, including concomitant, sequential, and hybrid therapies. We aimed to compare the cure rates achieved by these new therapy regimens.

Methods

This was a multicenter, open-label, pilot study enrolling consecutive non-ulcer dyspepsia patients with H. pylori infection never previously treated for the infection. Patients were randomized to receive one of the following treatments: (a) concomitant therapy: omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and tinidazole 500 mg for 5 days; (b) sequential therapy: omeprazole 20 mg and amoxicillin 1 g for 5 days followed by omeprazole 20 mg, clarithromycin 500 mg, and tinidazole 500 mg for 5 days; (c) hybrid therapy: omeprazole 20 mg, and amoxicillin 1 g for 7 days followed by omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and tinidazole 500 mg, for 7 days. All drugs were administered twice daily. Bacterial eradication was checked 6 weeks after treatment by using a ¹³C-urea breath test. A 10-day, second-line therapy with omeprazole 20 mg, levofloxacin 250 mg, and amoxicillin 1 g, all given twice daily, was offered to the eradication failure patients.

Results

Overall, 270 patients were enrolled, but 13 patients early interrupted treatment due to side effects. At intention-to-treat (ITT) and per-protocol analysis (PP), the eradication rates were 85.5% and 91.6% with the concomitant regimen, 91.1% and 92.1% with the sequential therapy, and 80% and 85.7% with the hybrid regimen. Differences were not statistically significant. H. pylori infection was cured in 10 (55.6%) patients with the second-line regimen.

Conclusion

In our study, both concomitant and sequential therapy, but not hybrid therapy, reached high eradication rates. The success rate of second-line levofloxacin-based triple therapy is decreasing.

Introduction

Helicobacter pylori eradication remains a challenge for the physicians, since no first-line regimen is able to cure the infection in all treated patients [1]. Unfortunately, the efficacy of standard triple therapies, still endorsed in current European guidelines, has decreased to unacceptable rates (< 80%) in different countries [2]. This has been largely attributed to increased antibiotic resistance [3], [4]. Therefore, the available antibiotics have been variably combined in novel regimens to increase H. pylori eradication rate and, so far, three therapies have been identified – i.e. the concomitant, the sequential, and the hybrid regimen [5]. The so-called “concomitant” regimen, firstly introduced in Germany on 1998 [6], has been recently reconsidered as first-line H. pylori eradication therapy [7]. The concomitant regimen is a quadruple therapy, including the standard triple therapy (PPI-clarithromycin-amoxicillin) plus metronidazole or tinidazole [8]. Different studies demonstrated a high (> 90%) efficacy of concomitant therapy, even when administered for only 5 days [6], [9], [10], [11], [12]. The so-called “sequential” therapy, consisting in a proton pump inhibitor (PPI) and amoxicillin for the first 5 days followed by a PPI, clarithromycin and tinidazole for the remaining 5 days, was pioneered in Italy in 2000 [13]. The superiority of such a therapy over the standard triple therapies has been widely documented [14]. More recently, a novel therapy regimen – named “hybrid” therapy − has been proposed, as a combination of the first phase of sequential regimen (dual therapy) with the concomitant schedule (quadruple therapy) [15]. Some studies found that the 7-day plus 7-day hybrid therapy may achieve high eradication rates [15], [16].

Based on these observations, a “head to head” comparison among these three effective therapy regimens is clinically relevant. We therefore designed a multicentre, pilot study, aiming to perform a direct comparison among concomitant, sequential, and hybrid therapies for H. pylori eradication in dyspeptic patients.

Section snippets

Patients

Two hundred and seventy consecutive patients complaining of dyspeptic symptoms referred for upper endoscopy were recruited in three centers. Exclusion criteria were:

•
age < 18 years;
•
previous H. pylori eradication attempts;
•
consumption of PPI and/or antibiotics in the previous month;
•
previous gastric surgery;
•
presence of either liver cirrhosis or kidney failure;
•
pregnancy;
•
known allergy to antibiotics.

For all the patients, written informed consent was obtained.

Endoscopy and H. pylori detection

At entry, all patients underwent endoscopy

Results

Overall, 270 consecutive patients were enrolled, including 30 patients for each therapeutic arm in the three centers. At entry, patients were comparable for age, sex distribution, and smoking habit (Table 1). No patient was lost to follow-up. Overall, 13 patients interrupted the treatment earlier due to side effects, whilst a good compliance (pill intake > 95%) was disclosed by the remaining patients. Therefore, the final PP population consisted of 257 patients.

Both ITT and PP H. pylori

Discussion

The progressive decrease of standard triple therapies efficacy has stimulated the identification of novel antibiotic combinations for H. pylori eradication. The concomitant schedule, the sequential therapy and, more recently, the hybrid regimen have been pinpointed by international researches with the aim of achieving H. pylori eradication in vast majority of patients at the first therapeutic attempt [1]. In this pilot study, we firstly compared the efficacy of these treatments in Italy,

Conclusion

This study found that concomitant and sequential therapy but not hybrid therapy, reached high eradication rates, and the incidence of side effects tended to be higher following both concomitant and hybrid therapy than sequential regimen. The levofloxacin-based second-line therapy achieved disappointingly low eradication rates.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgements

The authors are indebted to Rosa De Venuto, Paola De Benedictis, and Michele Persichella for skilful technical support.

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Modified sequential therapy regimens for Helicobacter pylori eradication: a systematic review
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Helicobacter pylori therapy: present and future
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Helicobacter pylori treatment in the era of increasing antibiotic resistance
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Worldwide H. pylori antibiotic resistance: a systematic review
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Mechanisms of Helicobacter pylori antibiotic resistance: an updated appraisal
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The optimal first-line therapy of Helicobacter pylori infection in year 2012
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Amoxicillin, metronidazole, omeprazole, clarithromycin: a new, short quadruple therapy for Helicobacter pylori eradication
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Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori
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Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing “concomitant therapy” versus triple therapy for Helicobacter pylori eradication
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There are more references available in the full text version of this article.

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Original articleConcomitant, sequential, and hybrid therapy for H. pylori eradication: A pilot study

Summary

Background and objective

Methods

Results

Conclusion

Introduction

Section snippets

Patients

Endoscopy and H. pylori detection

Results

Discussion

Conclusion

Disclosure of interest

Acknowledgements

Eur J Intern Med

Dig Liver Dis

Helicobacter pylori therapy: present and future

World J Gastrointest Pharmacol Ther

Helicobacter pylori treatment in the era of increasing antibiotic resistance

Gut

Worldwide H. pylori antibiotic resistance: a systematic review

J Gastrointestin Liver Dis

Mechanisms of Helicobacter pylori antibiotic resistance: an updated appraisal

World J Gastrointest Pathophysiol

The optimal first-line therapy of Helicobacter pylori infection in year 2012

Gastroenterol Res Pract

Amoxicillin, metronidazole, omeprazole, clarithromycin: a new, short quadruple therapy for Helicobacter pylori eradication

Helicobacter

Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori

Clin Exp Gastroenterol

Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing “concomitant therapy” versus triple therapy for Helicobacter pylori eradication

Helicobacter

Original article
Concomitant, sequential, and hybrid therapy for H. pylori eradication: A pilot study