• This record comes from PubMed

Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg)

. 2024 Dec 10 ; 74 (1) : 15-25. [epub] 20241210

Language English Country Great Britain, England Media electronic

Document type Journal Article, Observational Study

BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.

1st Clinical Medical Centre Kovrov Russian Federation

2nd Department of Internal Medicine Gastroenterology and Geriatrics University Hospital Olomouc Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc Czech Republic

ABS Manresa 3 Althaia Xarxa Assistencial Universitària de Manresa Institut de Recerca i Innovació en Ciències de la Vida i de la Salut de la Catalunya Central Manresa Barcelona Spain

Center for Research in Health Technologies and Information Systems Porto Portugal

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos 3 Madrid Spain

Department of Digestive Disorders Aberdeen Royal Infirmary Aberdeen UK

Department of faculty therapy and geriatrics Ural State Medical University Ekaterinburg Russian Federation

Department of Gastroenterology and Digestive Endoscopy Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Gastroenterology and Hepatology University Clinical Centre of Serbia Belgrade University Belgrade Serbia

Department of Gastroenterology AS Loginov Moscow Clinical Scientific Center Moscow Russian Federation

Department of Gastroenterology Centro Hospitalar do Porto Porto Portugal

Department of Gastroenterology Chelyabinsk Regional Clinical Hospital Chelyabinsk Russian Federation

Department of Gastroenterology DC Rogaska Rogaska Slatina Slovenia

Department of Gastroenterology Digestive Diseases Centre Riga Latvia

Department of Gastroenterology Hacettepe University Ankara Turkey

Department of Gastroenterology HC International Clinic Ankara Turkey

Department of Gastroenterology Hepatology and Infectious Diseases University Hospital of Magdeburg Magdeburg Germany

Department of Gastroenterology Hospital Clínic de Barcelona Barcelona Spain

Department of Gastroenterology Hospital Clínico Universitario Lozano Blesa Zaragoza Spain

Department of Gastroenterology Hospital General de Tomelloso Tomelloso Spain

Department of Gastroenterology Hospital Santos Reyes Aranda de Duero Spain

Department of Gastroenterology Hospital Universitario Costa del Sol Marbella Spain

Department of Gastroenterology Hospital Universitario de La Princesa Instituto de Investigación Sanitaria Princesa Madrid Spain

Department of Gastroenterology Hospital Universitario de Valme Sevilla Spain

Department of Gastroenterology Hospital Universitario La Moraleja Madrid Spain

Department of Gastroenterology Instituto de Investigación Sanitaria de Castilla La Mancha Tomelloso Spain

Department of Gastroenterology Kantonsspital Aarau Aarau Switzerland

Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania

Department of Gastroenterology Molinette SGAS Hospital Turin Italy

Department of Gastroenterology Østfold Hospital Trust Grålum Norway

Department of Gastroenterology Pomeranian Medical University Szczecin Poland

Department of Gastroenterology Rabin Medical Center Tel Aviv Israel

Department of Gastroenterology University Hospital of Split Split Croatia

Department of Gastroenterology University of Oviedo Oviedo Spain

Department of Hepato Gastroenterology and Digestive Oncology University Hospital of Nantes Nantes France

Department of Internal Medicine and Gastroenterology Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Department of Medicine Facultat de Ciències de la Salut Universitat de Vic Universitat Central de Catalunya Manresa Spain

Department of Outpatient Therapy and Family Medicine Tver State Medical University Tver Russian Federation

Department of Pancreatic Biliary and Upper Digestive Tract Disorders AS Loginov Moscow Clinical Scientific Center Moscow Russian Federation

Department of Propaedeutic of Internal Diseases and Gastroenterology Russian University of Medicine Moscow Russian Federation

Department of Surgery Transplantation and Gastroenterology Semmelweis University Budapest Hungary

Department of Surgery University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

Department of Therapy Azerbaijan State Advanced Training Institute for Doctors named by A Aliyev Baku Azerbaijan

Departments the Division for the Study of the Digestive diseases and its Comorbidity with Noncommunicable Diseases Government Institution L T Malaya Therapy National Institute of NAMS Kharkiv Ukraine

Dr Miriam and Sheldon G Adelson School of Medicine Ariel University Ari'el Israel

Faculty of Health Sciences Trinity College Dublin Dublin Ireland

Faculty of Medicine Universidad Francisco de Vitoria Madrid Spain

Gastrointestinal Oncology Endoscopy and Surgery Manresa Barcelona Spain

Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

Institute for Digestive Research and Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania

Institute of Clinical and Preventive Medicine University of Latvia Riga Latvia

Instituto De Ciências Biomédicas de Abel Salazar Universidade do Porto Porto Portugal

Instituto de Investigación Sanitaria de Aragón Zaragoza Spain

Medicina Programa de Doctorado en Ciencias de la Salud Universitat Internacional de Catalunya Sant Cugat del Valles Barcelona Spain

Redes de Investigación Cooperativa Orientada a Resultados en Salud Marbella Spain

School of Medicine Trinity College Dublin Dublin Ireland

Servei d'Aparell Digestiu Parc Taulí Hospital Universitari Institut d'Investigació i Innovació Parc Taulí Universitat Autònoma de Barcelona Sabadell Spain

Servei d'Urgències Parc Taulí Hospital Universitari Institut d'Investigació i Innovació Parc Taulí Universitat Autònoma de Barcelona Sabadell Spain

Tel Aviv University Tel Aviv Israel

The Centre for Digestive Diseases Endoklinika Szczecin Poland

Universidad Autónoma de Madrid Madrid Spain

Université de Bordeaux INSERM U1312 BRIC Bordeaux France

University of Barcelona Barcelona Spain

See more in PubMed

Hooi JKY, Lai WY, Ng WK, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153:420–9. doi: 10.1053/j.gastro.2017.04.022. PubMed DOI

Crowe SE. Helicobacter pylori Infection. N Engl J Med. 2019;380:1158–65. doi: 10.1056/NEJMcp1710945. PubMed DOI

Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6–30. doi: 10.1136/gutjnl-2016-312288. PubMed DOI

Megraud F, Coenen S, Versporten A, et al. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 2013;62:34–42. doi: 10.1136/gutjnl-2012-302254. PubMed DOI

Savoldi A, Carrara E, Graham DY, et al. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology. 2018;155:1372–82. doi: 10.1053/j.gastro.2018.07.007. PubMed DOI PMC

Gisbert JP, Calvet X. Review article: the effectiveness of standard triple therapy for Helicobacter pylori has not changed over the last decade, but it is not good enough. Aliment Pharmacol Ther. 2011;34:1255–68. doi: 10.1111/j.1365-2036.2011.04887.x. PubMed DOI

Graham DY, Lu H, Yamaoka Y. A report card to grade Helicobacter pylori therapy. Helicobacter. 2007;12:275–8. doi: 10.1111/j.1523-5378.2007.00518.x. PubMed DOI

Graham DY, Lee Y-C, Wu M-S. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014;12:177–86. doi: 10.1016/j.cgh.2013.05.028. PubMed DOI PMC

Dore MP, Leandro G, Realdi G, et al. Effect of pretreatment antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a meta-analytical approach. Dig Dis Sci. 2000;45:68–76. doi: 10.1023/a:1005457226341. PubMed DOI

Megraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut. 2004;53:1374–84. doi: 10.1136/gut.2003.022111. PubMed DOI PMC

Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther. 2007;26:343–57. doi: 10.1111/j.1365-2036.2007.03386.x. PubMed DOI

Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology. 2016;151:51–69. doi: 10.1053/j.gastro.2016.04.006. PubMed DOI

Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71:1724–62. doi: 10.1136/gutjnl-2022-327745. DOI

Gisbert JP, McNicholl AG. Optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. Helicobacter. 2017;22 doi: 10.1111/hel.12392. PubMed DOI

Gorbach SL. Bismuth therapy in gastrointestinal diseases. Gastroenterology. 1990;99:863–75. doi: 10.1016/0016-5085(90)90983-8. PubMed DOI

Liao J, Zheng Q, Liang X, et al. Effect of fluoroquinolone resistance on 14-day levofloxacin triple and triple plus bismuth quadruple therapy. Helicobacter. 2013;18:373–7. doi: 10.1111/hel.12052. PubMed DOI PMC

McNicholl AG, O’Morain CA, Megraud F, et al. Protocol of the European Registry on the management of Helicobacter pylori infection (Hp-EuReg) Helicobacter. 2019;24:e12630. doi: 10.1111/hel.12630. PubMed DOI

World Medical Association World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4. doi: 10.1001/jama.2013.281053. PubMed DOI

Guideline for good clinical practice E6. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r2-guideline-good-clinical-practice-step-5_en.pdf n.d. Available.

Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81. doi: 10.1016/j.jbi.2008.08.010. PubMed DOI PMC

Graham DY, Lu H, Dore MP. Relative potency of proton-pump inhibitors, Helicobacter pylori therapy cure rates, and meaning of double-dose PPI. Helicobacter. 2019;24:e12554. doi: 10.1111/hel.12554. PubMed DOI PMC

Kirchheiner J, Glatt S, Fuhr U, et al. Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol. 2009;65:19–31. doi: 10.1007/s00228-008-0576-5. PubMed DOI

Nyssen OP, Bordin D, Tepes B, et al. European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients. Gut. 2021;70:40–54. doi: 10.1136/gutjnl-2020-321372. PubMed DOI

Malfertheiner P, Bazzoli F, Delchier J-C, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. The Lancet . 2011;377:905–13. doi: 10.1016/S0140-6736(11)60020-2. PubMed DOI

Laine L, Hunt R, El-Zimaity H, et al. Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Am J Gastroenterol . 2003;98:562–7. doi: 10.1111/j.1572-0241.2003.t01-1-07288.x. PubMed DOI

Nyssen OP, McNicholl AG, Gisbert JP. Meta-analysis of three-in-one single capsule bismuth-containing quadruple therapy for the eradication of Helicobacter pylori. Helicobacter. 2019;24:e12570. doi: 10.1111/hel.12570. PubMed DOI

Mégraud F. The challenge of Helicobacter pylori resistance to antibiotics: the comeback of bismuth-based quadruple therapy. Therap Adv Gastroenterol. 2012;5:103–9. doi: 10.1177/1756283X11432492. PubMed DOI PMC

López-Góngora S, Puig I, Calvet X, et al. Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection. J Antimicrob Chemother. 2015;70:2447–55. doi: 10.1093/jac/dkv155. PubMed DOI

Lee YC, Dore MP, Graham DY. Diagnosis and Treatment of Helicobacter pylori Infection. Annu Rev Med. 2022;73:183–95. doi: 10.1146/annurev-med-042220-020814. PubMed DOI

Fisher ES, Goodman DC, Chandra A. Disparities in Health and Health Care Among Medicare Beneficiaries: A Brief Report of the Dartmouth Atlas Project. Lebanon (NH): The Dartmouth Institute for Health Policy and Clinical Practice; 2008. PubMed

Nyssen OP, Perez-Aisa A, Tepes B, et al. Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg) Am J Gastroenterol. 2021;116:1220–9. doi: 10.14309/ajg.0000000000001246. PubMed DOI

Nyssen OP, Perez-Aisa A, Castro-Fernandez M, et al. European Registry on Helicobacter pylori management: Single-capsule bismuth quadruple therapy is effective in real-world clinical practice. U Eur Gastroenterol J. 2021;9:38–46. doi: 10.1177/2050640620972615. PubMed DOI PMC

McNicholl AG, Bordin DS, Lucendo A, et al. Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients. Clin Gastroenterol Hepatol. 2020;18:89–98. doi: 10.1016/j.cgh.2019.03.048. PubMed DOI

Pérez-Aisa Á, Nyssen OP, Keco-Huerga A, et al. Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg) Gut. 2023;72:2031–8. doi: 10.1136/gutjnl-2022-329259. PubMed DOI

Murakami K, Sakurai Y, Shiino M, et al. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut. 2016;65:1439–46. doi: 10.1136/gutjnl-2015-311304. PubMed DOI PMC

See more in PubMed

ClinicalTrials.gov
NCT02328131

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...