- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02047994
Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality (GISTAR)
Study Overview
Status
Intervention / Treatment
Detailed Description
Gastric cancer is an important global public health issue in Eastern European regions, where the burden of the disease is substantial. There is sufficient epidemiological and experimental evidence that supports a causal link between H. pylori and gastric cancer. However, there is still limited evidence from clinical trials to prove whether H. pylori eradication with antimicrobial therapy is the approach of choice in entire infected populations or only in selected groups to reduce the risk of gastric cancer and whether eradication at advanced stages of atrophy is effective among these patients. The current European and global guidelines are proposing screening with pepsinogen tests as the best available tool to identify the individuals at increased risk for cancer development, yet there is insufficient evidence available on how effective these tests are in organized cancer screening settings.
We therefore propose to conduct a multi-center randomized trial in Latvia, Belarus and Russia, areas with high burden of the disease, with the main objective of evaluating if H. pylori screening followed by eradication in participants with positive result and endoscopy of those with serological evidence of atrophic gastritis can reduce gastric cancer mortality. The proposed trial will also investigate retrospectively if groups with chronic atrophic gastritis can select subjects who require treatment to achieve comparable gastric cancer reduction. Ultimately, this study will have the potential to find effective prevention strategies through identifying appropriate target groups that could get most benefits from the treatment.
The aim of this study is to search for new intervention strategies to decrease mortality from gastric cancer in high-risk areas.
The primary objective of the study is to determine if H. pylori screening followed by eradication of positive subjects and endoscopic follow-up of those with serological evidence of atrophic gastritis reduces mortality from gastric cancer in a high risk population among 40-64 years old subjects.
The secondary objectives are:
- To determine retrospectively if biomarkers of chronic atrophic gastritis or others can select the group of subjects who require treatment to achieve gastric cancer reduction comparable to the primary objective.
- To evaluate the rationale for volatile marker testing in exhaled breath for early identification of lesions in the stomach as well as other conditions related to increased risk.
- To evaluate the role of diet, lifestyle factors and environmental factors in the development of gastric lesions.
- To evaluate the impact of H. pylori eradication on selected medical conditions potentially associated with the infection (e.g. obesity, inflammatory bowel disease, dementia, circulatory diseases and esophageal diseases)
Methods: Approximately 30,000 men and women will be recruited into a randomized study. Eligible subjects between 40-64 years of age at entry who are residents in high gastric cancer incidence areas will be invited to participate in the trial by visiting one of the study clinics set up specifically for this trial.
For eligible participants who agree to participate and sign informed consent, a risk factor questionnaire will be administered and a complete medical evaluation will be performed at baseline.
Participants will be randomly assigned to either Group 1 (50%) or Group 2 (50%). Among those assigned to Group 1, H. pylori screening by detecting immunoglobulin G (IgG) group antibodies in plasma/serum and pepsinogen test will be performed. According to the results of the tests, participants will be assigned to H. pylori eradication treatment or upper endoscopy. Participants with serological evidence of atrophic gastritis (low pepsinogen I/II ratio) will undergo upper endoscopy with appropriate biopsy sampling as well as further follow-up with endoscopy according to MAPS (Management of precancerous conditions and lesions in the stomach) guidelines. H. pylori positive individuals will be offered standard eradication treatment as appropriate. From subjects in this group, breath samples will also be collected for volatile markers study by research nurses or junior physicians.
Participants assigned to Group 2 (50%) will constitute the control group, after having had a medical evaluation at the time of recruitment. During the follow-up period this group will be offered to consult a specialist when required due to clinical symptoms.
Both Group 1 and Group 2 will be offered fecal occult blood test (FOBT) as a benefit of study participation. Any participants who show a positive FOBT result will be referred to colonoscopy.
All the trial participants including Group 2 will be followed up at least for 15 years to collect systematic information on medical conditions, in particular gastric cancer and cause of death. A follow-up telephone call /alternative communication will be made every 5 years for outcome assessment.
The general study is preceded by a pilot-study that was conducted from October 2013 to December 2016 to test the assumptions as well as the tools and functionality of the study infrastructure. According to the results of the pilot study, required infrastructure and tools planned in the general study will be adapted accordingly.
Endpoints: The primary endpoint for our trial will be the mortality difference from gastric cancer between Group 1 and Group 2 at 15 years or when enough cases accumulate to demonstrate a statistical difference between the groups.
In addition to the mortality difference from gastric cancer between the two groups, other endpoints required to achieve the secondary objectives are listed below:
- The difference in gastric cancer incidence between Group 1 and Group 2
- The all-cause mortality difference between Group 1 and Group 2
- The difference in incidence and mortality of medical conditions between Group 1 and Group 2
- Sensitivity and specificity of pepsinogen tests to detect atrophy
- The proportion of gastric cancers arising in patients with non-atrophic vs. atrophic gastritis
- The proportion of cancers arising in patients with atrophy, but negative for H. pylori infection
- The difference in incidence of gastric cancer in the group with successful eradication when compared to those refusing/failing eradication within Group I
- The proportion of gastric cancer cases being identified during scheduled follow-up endoscopy out of the total number of cases in the follow-up group
- The differences in the test performance and disease prevalence between ethnic groups
- The performance (sensitivity, specificity, overall accuracy) of volatile marker testing approach to diagnose gastric cancer as well as premalignant lesions in the stomach
A pilot study with 3,455 participants was started in October 2013 and completed in December 2016 in Latvia.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Marcis Leja, MD, PhD
- Phone Number: +37 1 29 49 75 00
- Email: marcis.leja@lu.lv
Study Contact Backup
- Name: Jin Young Park, PhD
- Phone Number: +33 4 72 73 81 63
- Email: parkjy@iarc.fr
Study Locations
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-
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Riga, Latvia, LV-1050
- Recruiting
- Institute of Clinical and Preventive Medicine, University of Latvia
-
Contact:
- Marcis Leja, MD, PhD
- Phone Number: +37 1 29 49 75 00
- Email: cei@latnet.lv
-
Principal Investigator:
- Marcis Leja, MD, PhD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women aged 40-64 at the time of signing the consent form
- Willingness to get involved in the study irrespective in which of the study arms (after detailed information on the potential benefits and risks that this study may confer)
- The person has signed a consent form (including the acceptance of transporting the samples over the borders, as appropriate)
- To be in good health, as determined by a physical examination and history performed by a study physician at enrolment
Exclusion Criteria:
- Personal history of gastric cancer (prevalent gastric cancer cases will not be revealed at the time of inclusion, and therefore will be included)
- Gastric resections due to benign disease (ulcer suturing and vagotomy are accepted)
- H. pylori eradication therapy within 12 months prior to inclusion (irrespective of the treatment result)
- Presence of alarm symptoms for digestive or any other diseases (detailed in the questionnaire or during the physician evaluation)
- Pathological findings at physical investigation suggestive for a serious organic disease (physician evaluation)
- Serious co-morbid condition with life expectancy less than 5 years (physician evaluation)
- Factors otherwise limiting the participation according to the protocol conditions (problems of mobility, etc.)
- Serious psychological conditions/psychiatric disease limiting the possibilities to understand the requirements for diagnostic and/or medical interventions (physician evaluation)
- Low expectations on the compliance for the diagnostic work-up or treatment (physician evaluation)
- Expected loss for the follow-up (e.g. lack of communication possibilities and data entry in the registries, expected travel abroad, etc.) (physician evaluation)
- Signed consent form is not available
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1:Triple therapy
Among those assigned to Group 1, participants who are Helicobacter pylori positive will receive Triple therapy and/or upper endoscopy.
Participants with serological evidence of atrophic gastritis will undergo upper endoscopy and further endoscopic follow-up.
H. pylori positive individuals will be offered Helicobacter pylori eradication as appropriate, independently of the pepsinogen results.
From subjects in this group, breath samples will also be collected for volatile markers study.
In addition, fecal occult blood test (FOBT) will be offered to this group as a benefit to participate in the study.
|
Participants who are positive with Helicobacter pylori in Group1 will receive triple therapy.
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No Intervention: Group 2:No intervention
Those who assigned to Group 2 will receive no intervention and will be offered FOBT as a benefit of study participation.
Any participants who show positive FOBT will be referred to colonoscopy.
This will be the benefit to this group together with initial medical evaluation at the time of inclusion.
During the follow-up period this group will be offered to consult a specialist when required due to clinical symptoms.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gastric cancer mortality
Time Frame: 15 years
|
The primary objective of the study is to determine if H. pylori screening followed by eradication of positive subjects and endoscopic follow-up of those with serological evidence of atrophic gastritis reduces mortality from gastric cancer in a high risk population among 40-64 years old subjects.
|
15 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gastric cancer incidence
Time Frame: 15 years
|
The difference in gastric cancer incidence between Group 1 and Group 2 will be investigated
|
15 years
|
All-cause mortality
Time Frame: 15 years
|
The all-cause mortality difference between Group 1 and Group 2 will also be investigated.
|
15 years
|
Incidence of- and mortality from other medical conditions
Time Frame: 15 years
|
The impact of H. pylori eradication on selected medical conditions potentially associated with the infection (e.g.
obesity, inflammatory bowel disease, dementia, circulatory diseases and esophageal diseases) will be explored.
|
15 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Marcis Leja, MD, PhD, Professor, Institute of Clinical and Preventive Medicine, University of Latvia
- Principal Investigator: Jin Young Park, PhD, Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer
Publications and helpful links
General Publications
- Leja M, Cine E, Polaka I, Daugule I, Murillo R, Parshutin S, Razuka-Ebela D, Rotberga L, Anarkulova L, Krike P, Santare D, Tzivian L, Herrero R, Park JY. Factors influencing participation in preventive interventions for gastric cancer: the results from the GISTAR study. Eur J Cancer Prev. 2022 Mar 1;31(2):128-136. doi: 10.1097/CEJ.0000000000000682.
- Leja M, Park JY, Murillo R, Liepniece-Karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R. Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study. BMJ Open. 2017 Aug 11;7(8):e016999. doi: 10.1136/bmjopen-2017-016999.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12-36
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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