Original article
Alimentary tract
Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients

https://doi.org/10.1016/j.cgh.2019.03.048Get rights and content

Background & Aims

Due to the poor eradication rates of standard triple therapy, the addition of bismuth salts has been proposed for first-line eradication of Helicobacter pylori. We assessed the effectiveness and safety of the combination of bismuth and the standard, clarithromycin-containing triple therapy in eradication of H pylori infection, using data from a large multi-center registry.

Methods

We performed an interim analysis of data from the European Registry on H pylori Management, a prospective trial registering clinical data and outcomes from infected patients from 27 countries in Europe since 2013. We extracted data on 1141 treatment-naïve patients who received first-line treatment with bismuth salts (240 mg) and a proton pump inhibitor (57% received esomeprazole, 18% received omeprazole, 11% received pantoprazole, and 14% received rabeprazole), amoxicillin (1 g), and clarithromycin (500 mg), all taken twice daily.

Results

Intention to treat and per-protocol rates of eradication were 88% and 94%, respectively. Intention to treat eradication increased to 93% in patients who received 14-day treatments. Adverse events occurred in 36% of patients; 76% of these events were mild, with a mean duration of 6 days. In multivariate analysis, eradication was associated with treatment compliance (odds ratio [OR], 13.0), a double dose (equivalent to 40 mg omeprazole) of proton pump inhibitor (OR, 4.7), and 14-day duration of treatment (OR, 2.0).

Conclusions

In an analysis of data from a large multi-center registry, we found the addition of bismuth to 14-day standard triple therapy with clarithromycin and amoxicillin to eradicate H pylori infection in more than 90% of patients, based on intention to treat analysis, with an acceptable safety profile and level of adherence. ClinicalTrials.gov no: NCT02328131.

Section snippets

European Registry on Helicobacter pylori Management

This manuscript is an interim analysis of the current dataset of the European Registry on H pylori Management (Hp-EuReg), an international multicenter prospective noninterventional registry that will last more than 10 years (start date 2013). It has been promoted by the European Helicobacter and Microbiota Study Group (www.helicobacter.org). The study protocol is found in Supplementary Appendix 1.

Study Aim

The Hp-EuReg has as 1 of its aims allowing investigators to propose specific subanalyses of data;

Baseline Characteristics

In the Hp-EuReg, 1221 first-line treatments fitting the regimen (bismuth plus standard triple therapy) have been registered, and 1141 were valid for inclusion analysis after monitoring and quality controls (662 from Spain, 402 from Russia, and 77 from Ukraine). Flow chart diagram is shown in Figure 1. Ages ranged from 18 to 86 years old with a mean age of 49 years and a standard deviation of 15; a total of 59% were women. Indications for treatment were: dyspepsia in 57% (uninvestigated 18%,

Discussion

The present study reports H pylori ITT cure rates with bismuth plus PPI therapy around 90% in a large cohort of naive patients mainly from Spain. Of note, mean cure rates for 10-day triple therapy in Spain were recently estimated to be 70%–80%, similar to those reported in the database of the Hp-EuReg.19 Therefore, addition of bismuth salts to triple therapy in clinical practice resulted in a potential therapeutic gain (10%–20%) in populations with moderate to high clarithromycin resistance.

Acknowledgments

The authors thank the data monitors of the study, Mercedes Ramas (Hospital de La Princesa, Madrid, Spain), and Lorena Lee and Irene Barbado (Fundación Teófilo Hernando, Madrid, Spain) for their large efforts to ensure the validity of the data and quality of their work. They thank Pau Alarcón (Barcelona, Spain) who performed advanced data managing and programming for this project. They also thank the Spanish Association of Gastroenterology and the Scientific Director of the Spanish Association

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    Conflicts of interest These authors disclose the following: Adrian G. McNicholl has received wages from Allergan for formative actions. Ángeles Pérez-Aisa has served as a speaker; and has received wages from Allergan, Norgine, and Casen-Recordati for formative actions and advisory for Shionogi. Javier Molina-Infante has served as a speaker; and has received wages from Allergan, Almirall, and Casen Recordati for formative actions. Javier Alcedo has received wages from Allergan, Almirall, and Casen Recordati for formative actions. Javier P. Gisbert has served as a speaker, a consultant, and advisory member for or has received research funding from Almirall, Nycomed, AstraZeneca, Casen Recordati, and Allergan. The remaining authors disclose no conflicts.

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