Feasibility Study of the Proposed Test-and-treat Screening Program in Younger Participants With H. Pylori Infection

Helicobacter Pylori Infection Clinical Trial

Official title:

EU4Health Project Eurohelican: A Single-center Prospective Feasibility Study of the Proposed Test-and-treat Preventive Screening Program in Younger Slovenian Participants Aged 30-34 Years With or Without Helicobacter Pylori Infection

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06216639
• Other study ID #: EUROHELICAN01
• Status: Enrolling by invitation
• Start date: February 1, 2024
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: National Institute of Public Health, Slovenia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This prospective non-interventional study is being conducted as part of the EU4Health project Eurohelican. The main goal of this pilot study is to evaluate the feasibility and acceptability of implementing the proposed "test-and-treat" screening program on a population-based sample. Participants will be randomly selected from a younger population registered at the primary level of care and tested for the presence of active infection with Helicobacter pylori (H. pylori). Infected participants will undergo a bismuth-based quadruple treatment with antibiotics and a proton pump inhibitor, and will be controlled for eradication success by taking the urea breath test (UBT). A number of other participant outcomes will be also measured to provide additional pro et contra argumentation for the potential future implementation of a population-based test-and-treat screening program in Slovenia. Research reports will be disseminated and results will be presented to the public and scientific community to foster future developments in gastric cancer prevention.

Description:

Gastric cancer remains an important public health issue due to its high incidence rate and relatively low five-year survival rate. H. pylori infection has been found to be the main cause of gastric cancer and is responsible for 89% of non-cardia gastric cancers. There is also evidence that H. pylori eradication significantly reduces the incidence and mortality due to gastric cancer. According to the proposal based on available data, the population-based test-and-treat screening program may be the best available evidence-based intervention to prevent the occurrence of gastric cancer. In its recommendations from September 9th 2023, the European Council also supported the implementation of a screening program particularly in European regions with an increased prevalence of H. pylori and incidence of gastric cancer. The aim of this study is to scientifically evaluate the feasibility, acceptability and effectiveness of the proposed population-based test-and-treat strategy for the eradication of H. pylori infection.

The proposed test-and-treat strategy is targeted at the population around the age of 30 years who are infected with H. pylori and predominantly asymptomatic. The main questions it aims to answer are:

• Is the proposed population-based H. pylori test-and-treat strategy feasible and acceptable in a community health service setting?

• Is the proposed population-based H. pylori test-and-treat strategy effective in a community health service setting?

• What is the profile of adverse events in the treated participants?

Participants will be randomly selected from the population pool of individuals aged 30-34 years who have a chosen personal physician at Community Healthcare Center dr. Adolf Drolc Maribor (HCM). Enrolled participants who will give their informed consent will be interviewed by a registered nurse regarding risk factors for developing H. pylori infection and selected lifestyle habits. In addition, serology testing for the presence of H. pylori antibodies will be performed on all participants. Participants with a positive serology result will be given a confirmatory urea breath test (UBT). Those participants with a confirmed active H. pylori infection will be treated with bismuth-based quadruple therapy, and the success of eradication will then be verified by UBT one month after the treatment. Participants with a positive result of the second UBT will be treated again with a second-line modified bismuth-based quadruple therapy, and the success of eradication will be verified by UBT. Compliance with testing and treatment, treatment outcomes, adverse events and reasons for withdrawing participation will be monitored for each of the participants. The feasibility and sustainability of the proposed test-and-treat strategy will be evaluated using several key performance indicators that follow the structure of five principal areas of feasibility. Data will be entered into the REDCap online survey application and analyzed using IBM SPSS Statistics software.

The results of this study will enable to potentially scale up the project to the national level and present a potential model for the implementation of this strategy in Europe. Second, the results will contribute to the implementation of the Europe's Beating Cancer Plan goal of preventing gastric cancers caused by H. pylori infections. Finally, this study will provide additional real-world data for the preparation of Expert Working Group Report of the International Agency for Research on Cancer of the World Health Organization (IARC/WHO), which will include a minimum set of standards for the implementation of a population-based screening program at the international level.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 2000
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 34 Years

Eligibility

Inclusion Criteria:

• Individuals aged 30-34 years,

• Individuals who have a chosen personal physician at HCM,

• Individuals who sign an informed consent to participate, and

• Individuals who do not have a congenital or acquired intellectual disability.

Exclusion Criteria:

• Individuals younger than 30 years or older than 34 years,

• Individuals who do not have a chosen personal physician at HCM,

• Individuals who do not sign informed consent for participation,

• Individuals with intellectual or developmental limitations who are unable to provide a fully-informed consent to participate (based on the assessment of the patient's primary care team)

• Individuals who were previously treated for H. pylori infection, and

• Individuals with a history of partial of total gastric resection due to benign or malign lesions.

Related Conditions & MeSH terms

• Communicable Diseases
• Helicobacter Infections
• Helicobacter Pylori Infection
• Infections

Intervention

Drug:
• Bismuth Subcitrate
Tripotassium dicitratobismuthate 120 mg film-coated tablets. Prescribed for both primary and (potential) secondary treatment with bismuth-based quadruple therapy in participants with active H. pylori infection. The prescribed daily dose is 120 mg QID for a period of 14 days.
• Esomeprazole
Esomeprazol 40 mg gastro-resistant tablets or hard capsules. Which one of the three brands is prescribed for an individual participant in this prospective study depends on the decision of a chosen personal physician. Prescribed for both primary and (potential) secondary treatment with bismuth-based quadruple therapy in participants with active H. pylori infection. The prescribed daily dose is 40 mg BID for a period of 14 days.
• Metronidazole
Metronidazol 400 mg tablets. Prescribed for both primary and (potential) secondary treatment with bismuth-based quadruple therapy in participants with active H. pylori infection. The prescribed daily dose is 400 mg QID for a period of 14 days.
• Amoxicillin
Amoxicillin 500 mg dispersible tablets or hard capsules. Which one of the two brands is prescribed for an individual participant in this prospective study depends on the decision of a chosen personal physician. Prescribed only for the primary treatment with bismuth-based quadruple therapy in participants with active H. pylori infection who are not allergic to penicillin. The prescribed daily dose is 500 mg QID for a period of 14 days.
• Clarithromycin
Clarithromycin 500 mg film-coated tablets. Prescribed only for the primary treatment with bismuth-based quadruple therapy in participants with active H. pylori infection who are allergic to penicillin. The prescribed daily dose is 500 mg BID for a period of 14 days.
• Levofloxacin
Levofloxacin 500 mg film-coated tablets. Prescribed only for the (potential) secondary treatment with bismuth-based quadruple therapy in participants with active H. pylori infection. The prescribed daily dose is 500 mg OID for a period of 14 days.

Locations

Country	Name	City	State
Slovenia	Community Healthcare Center dr. Adolf Drolc Maribor (HCM)	Maribor

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Public Health, Slovenia	Community Healthcare Center dr. Adolf Drolc Maribor (HCM)

Country where clinical trial is conducted

Slovenia, 

References & Publications (17)

Bowen DJ, Kreuter M, Spring B, Cofta-Woerpel L, Linnan L, Weiner D, Bakken S, Kaplan CP, Squiers L, Fabrizio C, Fernandez M. How we design feasibility studies. Am J Prev Med. 2009 May;36(5):452-7. doi: 10.1016/j.amepre.2009.02.002. — View Citation

Chiang TH, Chang WJ, Chen SL, Yen AM, Fann JC, Chiu SY, Chen YR, Chuang SL, Shieh CF, Liu CY, Chiu HM, Chiang H, Shun CT, Lin MW, Wu MS, Lin JT, Chan CC, Graham DY, Chen HH, Lee YC. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands. Gut. 2021 Feb;70(2):243-250. doi: 10.1136/gutjnl-2020-322200. Epub 2020 Aug 13. — View Citation

de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020 Feb;8(2):e180-e190. doi: 10.1016/S2214-109X(19)30488-7. Epub 2019 Dec 17. — View Citation

Ford AC, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut. 2020 Dec;69(12):2113-2121. doi: 10.1136/gutjnl-2020-320839. Epub 2020 Mar 23. — View Citation

Kowada A. A Population-Based Helicobacter pylori Eradication Strategy Is More Cost-Effective than Endoscopic Screening. Dig Dis Sci. 2023 May;68(5):1735-1746. doi: 10.1007/s10620-022-07795-z. Epub 2022 Dec 24. — View Citation

Lansdorp-Vogelaar I, Sharp L. Cost-effectiveness of screening and treating Helicobacter pylori for gastric cancer prevention. Best Pract Res Clin Gastroenterol. 2013 Dec;27(6):933-47. doi: 10.1016/j.bpg.2013.09.005. Epub 2013 Sep 27. — View Citation

Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS, Graham DY. Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis. Gastroenterology. 2016 May;150(5):1113-1124.e5. doi: 10.1053/j.gastro.2016.01.028. Epub 2016 Feb 2. — View Citation

Lee YC, Chiang TH, Liou JM, Chen HH, Wu MS, Graham DY. Mass Eradication of Helicobacter pylorito Prevent Gastric Cancer: Theoretical and Practical Considerations. Gut Liver. 2016 Jan;10(1):12-26. doi: 10.5009/gnl15091. — View Citation

Liou JM, Malfertheiner P, Lee YC, Sheu BS, Sugano K, Cheng HC, Yeoh KG, Hsu PI, Goh KL, Mahachai V, Gotoda T, Chang WL, Chen MJ, Chiang TH, Chen CC, Wu CY, Leow AH, Wu JY, Wu DC, Hong TC, Lu H, Yamaoka Y, Megraud F, Chan FKL, Sung JJ, Lin JT, Graham DY, Wu MS, El-Omar EM; Asian Pacific Alliance on Helicobacter and Microbiota (APAHAM). Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus. Gut. 2020 Dec;69(12):2093-2112. doi: 10.1136/gutjnl-2020-322368. Epub 2020 Oct 1. — View Citation

Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5. — View Citation

Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study group. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Aug 8:gutjnl-2022-327745. doi: 10.1136/gutjnl-2022-327745. Online ahead of print. — View Citation

Ozeki K, Asano M, Furuta T, Ojima T. Relationship between primary eradication of Helicobacter pylori and drinking habits in women: collaborative research between a pharmacy and a clinic. Epidemiol Infect. 2019 Oct 22;147:e292. doi: 10.1017/S0950268819001730. — View Citation

Park JY, Herrero R. Recent progress in gastric cancer prevention. Best Pract Res Clin Gastroenterol. 2021 Mar-Apr;50-51:101733. doi: 10.1016/j.bpg.2021.101733. Epub 2021 Feb 18. — View Citation

Sarmasti M, Khoshbaten M, Khalili F, Yousefi M. Cost-Effectiveness of Screening Helicobacter pylori for Gastric Cancer Prevention: a Systematic Review. J Gastrointest Cancer. 2022 Dec;53(4):1093-1103. doi: 10.1007/s12029-021-00726-7. Epub 2021 Oct 25. — View Citation

Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8. — View Citation

Tan Y, Wei Z, Liu K, Qin Y, Hui W. Lifestyle habits and gastric cancer in an East Asian population: a Mendelian randomization study. Front Oncol. 2023 Sep 4;13:1224753. doi: 10.3389/fonc.2023.1224753. eCollection 2023. — View Citation

Yu J, Yang P, Qin X, Li C, Lv Y, Wang X. Impact of smoking on the eradication of Helicobacter pylori. Helicobacter. 2022 Feb;27(1):e12860. doi: 10.1111/hel.12860. Epub 2021 Oct 27. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Healthcare workers' assessment of feasibility and acceptability of the proposed practical implementation of a screening program	Responses to qualitative questions and summary statistics from a post-enrollment questionnaire for healthcare workers involved into the implementation of the screening program. The questionnaires will be completed by up to 100 chosen personal physicians and registered nurses from HCM who participated in this prospective study. Questionnaire preparation follows the key performance indicators for assessing the five dimensions of the standardized TELOS framework of project feasibility.	1 year after the completion of prospective study.
Secondary	Participation rate of subjects selected for the program	Subtraction of 1) study participants who: did not respond to an invitation,; signed the informed consent form but were not included in the study due to exclusion criteria,; declined to take a serology test,; declined to take any of the UBTs as specified in the study protocol,; had their therapy postponed due to maternity reasons,; declined to be re-treated after the treatment failure of primary therapy,; voluntarily withdrew at any time during their participation in the study,; withdrew from the study within points a)-g) combined,; from 2) all participants invited in the study.; The participation rate is measured in frequencies and percentage points (%).	3 months after: a) completion of the enrollment process (points a)-d)); b) completion of the prospective study (points e)-h)).
Secondary	Eradication rate of infection with H. pylori	Subtraction of 1) participants who were subjected to treatment failure of the primary therapy regimen from 2) all participants with an active H. pylori infection who underwent the primary bismuth-based quadruple therapy regimen.; The eradication rate is measured in frequencies and percentage points (%).	3 months after enrollment of the last participant who took a control UBT after the completion of primary bismuth-based quadruple therapy regimen.
Secondary	Description of the adverse events profile	Qualitative records of all self-reported (or physician-reported) adverse events during and after primary (or secondary) bismuth-based quadruple therapy regimen. All non-serious or serious adverse event will be reported.	6 months after enrollment of the last participant who took a second control UBT after the completion of secondary bismuth-based quadruple therapy regimen.