European Registry on the Management of Helicobacter Pylori Infection

H. Pylori Infection Clinical Trial

Official title:

European Registry on the Management of Helicobacter Pylori Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02328131
• Other study ID #: Hp-EuReg
• Status: Recruiting
• Start date: June 2013
• Est. completion date: December 2024

Study information

• Verified date: February 2023
• Source: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Contact: Javier Pérez Gisbert, MD
• Phone: +34 913093911
• Email: javier.p.gisbert[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The great diversity of regimens and treatment lines, the different efficacy of these, mostly due to the increase in bacterial antibiotic resistance and regional differences, requires a continuous critical analysis of clinical practice, evaluating systematically the efficacy and safety of the different regimens and the cost-effectiveness of the different diagnostic-therapeutic strategies. This will help in the design of an efficient and optimized treatment that will reduce number of re-treatments, diagnostic tests and the appearance of associated pathologies such as peptic ulcers, gastrointestinal bleeding and, probably, gastric cancers. Therefore, the evaluation of real clinical practice using non-interventionist registries will help to improve the design and organization of European Consensus on the management of H. pylori infection, which is the best way to establish healthcare efficiency.

Primary aim

To obtain a database registering systematically over a year a large and representative sample of routine clinical practice of European gastroenterologists in order to produce descriptive studies of the management of H. pylori infection.

Secondary aims

1. To evaluate H. pylori infection consensus and clinical guidelines implementation in different countries.

2. To perform studies focused on epidemiology, efficacy and safety of the commonly used treatments to eradicate H. pylori.

3. To evaluate accessibility to healthcare technologies and drugs used in the management of H. pylori infection.

4. To allow the development of partial and specific analysis by the participating researchers after approval by the Registry's Scientific Committee

Methodology Non-interventionist prospective multicentre international registry promoted by the European Helicobacter Study Group. A renowned gastroenterologist from each country was selected as Local Coordinator (30 countries). They will in turn select up to ten gastroenterologists per country that will register the routine clinical practice consultations they receive over 10 years in an electronic Case Report Form (e-CRF). Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation and outcome data. The database will allow researchers to perform specific subanalysis after approval by the Scientific Committee of the study.

Description:

Abstract

Introduction: H. pylori selectively infects the human stomach mucosa, being the most prevalent chronic infection in the world. Its prevalence correlates with socioeconomic factors and it is higher in older individuals. H. pylori presence causes chronic gastritis in 100% of infected patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease and gastric cancer; it is for this reason that from a public health standpoint it is considered a high impact pathogen, responsible of a significant morbidity and mortality. Nowadays there are Consensus and Clinical Guidelines regarding the infection management at a European level and in most of the states, but no data have shown the level of implementation of these recommendations. The high costs that this infection carries both socially and to the health system require the continuous and systematic assessment of the diagnostic and treatment strategies, as well as the accessibility to diagnostic methods and most efficient drugs.

Aim: To register the treatment, diagnosis and management strategies of H. pylori infected adult patients in the Digestive Services outpatient clinics throughout Europe.

Methods: Non-interventionist prospective multicentre international registry promoted by the European Helicobacter Study Group. A renowned gastroenterologist from each country was selected as Local Coordinator (30 countries). They will in turn select up to ten gastroenterologists per country that will register the routine clinical practice consultations they receive over 10 years in an electronic Case Report Form (e-CRF). Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation and outcome data. The database will allow researchers to perform specific subanalysis after approval by the Scientific Committee of the study.

INTRODUCTION

H. pylori presence causes chronic gastritis in 100% of infected patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease and gastric cancer. H. pylori eradication prevents peptic ulcer recurrence and its complications, and decreases the incidence of gastric cancer. H. pylori eradication in patients with peptic ulcer or even functional or non-investigated dyspepsia is a cost-effective strategy.

The most common clinical manifestation of H. pylori infection is dyspepsia, a major health problem, whose prevalence reaches more than 10% among adult populations with its attendant burden of morbidity and health system costs in diagnosis and treatment. Approximately 20% to 30% of people in the community each year report chronic or recurrent dyspeptic symptoms, and consultations for dyspepsia account for up to 40% of referrals among gastroenterology outpatients, the "test-and-treat" strategy being the most cost-effective. Moreover, H. pylori is the major cause of peptic ulcer disease, causing over 90% of duodenal and 70% of gastric ulcers. Considerable evidence supports that the nature of the chronic inflammatory process driven by H. pylori is of critical importance in gastric carcinogenesis (adenocarcinoma and mucosa-associated lymphoid tissue -MALT- lymphoma). It is for that reason that the WHO's International Agency for Research on Cancer classified H. pylori as a group 1 (definite) carcinogen.

Scientific evidence demonstrates that diagnosis and eradication of H. pylori is the most cost-effective strategy in the management of dyspepsia, peptic ulcer and gastric cancer prevention. The treatment regimens are very diverse and have changed overtime. Monotherapies and treatments with two drugs did not achieve acceptable eradication rates. The commonly recommended regimen in most Consensus Conferences is the standard triple regimen, combining two antibiotics (clarithromycin with amoxicillin or metronidazole) and a proton pump inhibitor (PPI) for 7 to 14 days. Another recommended alternative is bismuth-containing quadruple therapy (PPI, tetracycline, metronidazole and bismuth salts). In the last years, results with new and efficient rescue regimens including levofloxacin have been published. Lately, new treatments have been proposed, including non-bismuth quadruple regimens, with two main variants: the "sequential" treatment (an induction phase with PPI and amoxicillin and a second phase with PPI, clarithromycin and metronidazole) and the "concomitant" treatment (same four drugs taken altogether).

The great diversity of regimens and treatment lines, the different efficacy of these, mostly due to the increase in bacterial antibiotic resistance and regional differences, requires a continuous critical analysis of clinical practice, evaluating systematically the efficacy and safety of the different regimens and the cost-effectiveness of the different diagnostic-therapeutic strategies. This will help in the design of an efficient and optimized treatment that will reduce number of re-treatments, diagnostic tests and the appearance of associated pathologies such as peptic ulcers, gastrointestinal bleeding and, probably, gastric cancers. Therefore, the evaluation of real clinical practice using non-interventionist registries will help to improve the design and organization of European Consensus on the management of H. pylori infection, which is the best way to establish healthcare efficiency.

AIMS

Primary aim To obtain a database registering systematically over a year a large and representative sample of routine clinical practice of European gastroenterologists in order to produce descriptive studies of the management of H. pylori infection.

Secondary aims

1. To evaluate H. pylori infection consensus and clinical guidelines implementation in different countries.

2. To perform studies focused on epidemiology, efficacy and safety of the commonly used treatments to eradicate H. pylori.

3. To evaluate accessibility to healthcare technologies and drugs used in the management of H. pylori infection.

4. To allow the development of partial and specific analysis by the participating researchers after approval by the Registry's Scientific Committee.

METHODS

International multicenter prospective non-interventionist registry promoted by the European Helicobacter Study Group.

Scientific Committee

• Javier P. Gisbert (President)

• Francis Megraud

• Colm O'Morain

• Adrian G. McNicholl

Local Coordinators

A list of European Countries has been selected. Included countries were those having at least ten clinical research publications in PubMed regarding H. pylori infection.

In each country a Local Coordinator was selected based on its clinical and research activity (Table I).

The Local Coordinators will constitute the monitoring and drafting committee of the registry.

The Local Coordinators will be in charge of selecting up to 10 recruiting investigators in each country and will be in charge of the follow up and quality of the recruiting; they will be the link between promoters and recruiting investigators.

Recruiter Investigators

The Recruiting Investigators must be gastroenterologists attending an adult population with a gastroenterology outpatient clinic that assists H. pylori infected patients. Before acceptance the outpatient clinic must attend, in a clinical routine basis, patients in which H. pylori diagnosis or treatment is indicated. Eradication confirmation tests have to be performed routinely. They will register the study variables of their own routine clinical practice in an e-CRF.

Study Variables

Anonymised Patient Identifiers

• Country/Centre/Investigator

• Autonumeric Patient identifier number

• Gender

• Date of Birth

• Ethnic Background History and Comorbidity

• Drug allergies

• Relevant comorbidities

• Current concomitant medication Data on Infection

• Indication for diagnosis and treatment

• Upper Gastrointestinal tract symptoms

• Diagnostic Test for current treatment

• Number and type of previous eradication attempts Prescribed Treatment

• Drugs

• Dosage and intakes per day

• Length of treatment Compliance

• Adherence to treatment (yes/no >90%) Adverse Events

• Type of event, intensity, duration and relation with treatment

• Treatment withdrawal due to adverse events. Efficacy

• Eradication (yes/no), test used, and date

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Infected adult patients by Helicobacter pylori

Exclusion Criteria:

Related Conditions & MeSH terms

• Communicable Diseases
• H. Pylori Infection
• Infections

Locations

Country	Name	City	State
Austria	Medical University Wien	Wien
Belgium	CHU de Charleroi, Charleroi	Charleroi
Bulgaria	Medical University of Sofia	Sofia
Croatia	University Hospital Merkur	Zagreb
Czechia	Charles University Faculty of Medicine	Prague
Denmark	Køge University Hospital	Køge
Estonia	University of Tartu	Tartu
Finland	Herttoniemi Hospital, Helsinki	Helsinki
France	Hôpital Pellegrin	Bordeaux
Germany	Medizin Uni Magdeburg	Magdeburg
Greece	Gastroenterology Clinic, Henry Dunant Hospital	Athens
Hungary	Ferencváros Health Centre, Gaastroenterology	Budapest
Ireland	Adelaide Meath Hospital, Dublin	Dublin
Italy	Studio Gasbarrini	Roma
Latvia	Digestive Diseases Centre GASTRO	Riga
Lithuania	Lithuanian university of Health Sciences Hospital	Kaunas
Netherlands	Ikazia Ziekenhuis/ Erasmus Medisch Centrum	Rotterdam
Norway	Central Hospital of Ostfold	Fredrikstad
Poland	Departament of Gastroenterology, Medical Centre for Postgraduate Education	Warsaw
Portugal	Porto	Porto
Romania	Timisoara	Timisoara
Russian Federation	Central Scientific Research Institute of Gastroenterology	Moscow
Serbia	Clinical Center of Serbia	Belgrade
Slovenia	DC Rogaska	Rogaska Slatina
Spain	Hospital de La Princesa, Madrid	Madrid
Sweden	Uppsala University Hospital.	Uppsala
Switzerland	University Hospital Basel	Basel
Turkey	Dokuz Eylul University School of Medicine	Izmir
Ukraine	National Medical University	Kiev
United Kingdom	Leeds General Infirmiry Hospital	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Javier P. Gisbert

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  Croatia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Latvia,  Lithuania,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovenia,  Spain,  Sweden,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (24)

Arkkila PE, Seppala K, Kosunen TU, Sipponen P, Makinen J, Rautelin H, Farkkila M. Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers. Eur J Gastroenterol Hepatol. 2005 Jan;17(1):93-101. doi: 10.1097/00042737-200501000-00018. — View Citation

Azevedo NF, Huntington J, Goodman KJ. The epidemiology of Helicobacter pylori and public health implications. Helicobacter. 2009 Sep;14 Suppl 1:1-7. doi: 10.1111/j.1523-5378.2009.00703.x. Erratum In: Helicobacter. 2010 Feb;15(1):78. — View Citation

Broutet N, Tchamgoue S, Pereira E, Lamouliatte H, Salamon R, Megraud F. Risk factors for failure of Helicobacter pylori therapy--results of an individual data analysis of 2751 patients. Aliment Pharmacol Ther. 2003 Jan;17(1):99-109. doi: 10.1046/j.1365-2036.2003.01396.x. — View Citation

de Vries AC, van Grieken NC, Looman CW, Casparie MK, de Vries E, Meijer GA, Kuipers EJ. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology. 2008 Apr;134(4):945-52. doi: 10.1053/j.gastro.2008.01.071. Epub 2008 Jan 30. — View Citation

Ford A, Moayyedi P. How can the current strategies for Helicobacter pylori eradication therapy be improved? Can J Gastroenterol. 2003 Jun;17 Suppl B:36B-40B. doi: 10.1155/2003/714124. — View Citation

Ford AC, Axon AT. Epidemiology of Helicobacter pylori infection and public health implications. Helicobacter. 2010 Sep;15 Suppl 1:1-6. doi: 10.1111/j.1523-5378.2010.00779.x. — View Citation

Gisbert JP, Calvet X, O'Connor A, Megraud F, O'Morain CA. Sequential therapy for Helicobacter pylori eradication: a critical review. J Clin Gastroenterol. 2010 May-Jun;44(5):313-25. doi: 10.1097/MCG.0b013e3181c8a1a3. — View Citation

Gisbert JP, Calvet X. Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther. 2011 Sep;34(6):604-17. doi: 10.1111/j.1365-2036.2011.04770.x. Epub 2011 Jul 11. — View Citation

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 Dec;34(11-12):1255-68. doi: 10.1111/j.1365-2036.2011.04887.x. Epub 2011 Oct 21. — View Citation

Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Munoz JE. H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Cochrane Database Syst Rev. 2004;(2):CD004062. doi: 10.1002/14651858.CD004062.pub2. — View Citation

Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 2010 Aug;59(8):1143-53. doi: 10.1136/gut.2009.192757. Epub 2010 Jun 4. — View Citation

Graham DY, Rimbara E. Understanding and appreciating sequential therapy for Helicobacter pylori eradication. J Clin Gastroenterol. 2011 Apr;45(4):309-13. doi: 10.1097/MCG.0b013e31820ac05e. — View Citation

Greenberg ER, Anderson GL, Morgan DR, Torres J, Chey WD, Bravo LE, Dominguez RL, Ferreccio C, Herrero R, Lazcano-Ponce EC, Meza-Montenegro MM, Pena R, Pena EM, Salazar-Martinez E, Correa P, Martinez ME, Valdivieso M, Goodman GE, Crowley JJ, Baker LH. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet. 2011 Aug 6;378(9790):507-14. doi: 10.1016/S0140-6736(11)60825-8. Epub 2011 Jul 21. — View Citation

Hsu PI, Wu DC, Wu JY, Graham DY. Is there a benefit to extending the duration of Helicobacter pylori sequential therapy to 14 days? Helicobacter. 2011 Apr;16(2):146-52. doi: 10.1111/j.1523-5378.2011.00829.x. — View Citation

Ikenberry SO, Harrison ME, Lichtenstein D, Dominitz JA, Anderson MA, Jagannath SB, Banerjee S, Cash BD, Fanelli RD, Gan SI, Shen B, Van Guilder T, Lee KK, Baron TH; ASGE STANDARDS OF PRACTICE COMMITTEE. The role of endoscopy in dyspepsia. Gastrointest Endosc. 2007 Dec;66(6):1071-5. doi: 10.1016/j.gie.2007.07.007. Epub 2007 Oct 29. No abstract available. — View Citation

Maconi G, Sainaghi M, Molteni M, Bosani M, Gallus S, Ricci G, Alvisi V, Porro GB. Predictors of long-term outcome of functional dyspepsia and duodenal ulcer after successful Helicobacter pylori eradication--a 7-year follow-up study. Eur J Gastroenterol Hepatol. 2009 Apr;21(4):387-93. doi: 10.1097/MEG.0b013e3283069db0. — View Citation

Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012 May;61(5):646-64. doi: 10.1136/gutjnl-2012-302084. — View Citation

McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010 Apr 29;362(17):1597-604. doi: 10.1056/NEJMcp1001110. No abstract available. — View Citation

McNicholl AG, Linares PM, Nyssen OP, Calvet X, Gisbert JP. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2012 Sep;36(5):414-25. doi: 10.1111/j.1365-2036.2012.05211.x. Epub 2012 Jul 15. — View Citation

Moayyedi P, Deeks J, Talley NJ, Delaney B, Forman D. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol. 2003 Dec;98(12):2621-6. doi: 10.1111/j.1572-0241.2003.08724.x. — View Citation

Moayyedi P. The health economics of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol. 2007;21(2):347-61. doi: 10.1016/j.bpg.2006.11.004. — View Citation

Niv Y, Hazazi R. Helicobacter pylori recurrence in developed and developing countries: meta-analysis of 13C-urea breath test follow-up after eradication. Helicobacter. 2008 Feb;13(1):56-61. doi: 10.1111/j.1523-5378.2008.00571.x. — View Citation

Oderda G, Shcherbakov P, Bontems P, Urruzuno P, Romano C, Gottrand F, Gomez MJ, Ravelli A, Gandullia P, Roma E, Cadranel S, De Giacomo C, Canani RB, Rutigliano V, Pehlivanoglu E, Kalach N, Roggero P, Celinska-Cedro D, Drumm B, Casswall T, Ashorn M, Arvanitakis SN; European Pediatric Task Force on Helicobacter pylori. Results from the pediatric European register for treatment of Helicobacter pylori (PERTH). Helicobacter. 2007 Apr;12(2):150-6. doi: 10.1111/j.1523-5378.2007.00485.x. — View Citation

Rokkas T, Sechopoulos P, Robotis I, Margantinis G, Pistiolas D. Cumulative H. pylori eradication rates in clinical practice by adopting first and second-line regimens proposed by the Maastricht III consensus and a third-line empirical regimen. Am J Gastroenterol. 2009 Jan;104(1):21-5. doi: 10.1038/ajg.2008.87. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prescribed treatment for H. pylori	Drugs; Dosage and intakes; Length of treatment	1 year
Secondary	Adverse Events	Type, intensity, duration and relation with treatment; Treatment withdrawal due to adverse event	1 year
Secondary	Efficacy of treatment	Eradication (yes/no), test used and date	1 year
Secondary	Anonymised patient identifiers	Country/Centre/Investigator; Autonumeric Patient identifier number; Gender; Date of Birth; Ethnic Background	1 year