<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03231332</url>
  </required_header>
  <id_info>
    <org_study_id>1.1.1.1/16/A/272</org_study_id>
    <nct_id>NCT03231332</nct_id>
  </id_info>
  <brief_title>Effects of H.Pylori Eradication on Microbiome</brief_title>
  <official_title>Long Term Effects of H.Pylori Eradication on Microbiome and Adverse Events</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Latvia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Latvian Biomedical Research and Study Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Latvia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this Project is, within the scope of industrial research, to evaluate the long&#xD;
      term effects of H.pylori eradication on microbiome (gut microbiome, upper respiratory tract&#xD;
      microbiome) and lasting adverse events. In addition, the project aims to evaluate its effects&#xD;
      on abundance and prevalence of extended-spectrum beta-lactamases coding genes and develop&#xD;
      cost effective ESBL screening test prototype.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current international guidelines and expert working groups are encouraging&#xD;
      &quot;search-and-treat&quot; strategy for H.pylori to prevent gastric cancer1, 2. The highest yield of&#xD;
      this approach is expected in countries with high incidence of gastric cancer and high&#xD;
      prevalence of H.pylori infection. This approach will be further supported by the Maastricht V&#xD;
      European guidelines (manuscript in preparation). The rationale for this approach is that 1-2%&#xD;
      of the infected individuals are developing gastric cancer; the International Agency for&#xD;
      Research on Cancer has classified H.pylori infection as Class I carcinogen3, 4. A study in&#xD;
      Matsu island with high gastric cancer risk has suggested that gastric cancer incidence can be&#xD;
      decreased by 25% by such strategy5; the limitations, however, include lack of the control&#xD;
      group.&#xD;
&#xD;
      Three recent meta-analysis have confirmed the cost-effectiveness of such approach6-8; of&#xD;
      course, those are based on the limited currently available data on potential risks caused by&#xD;
      population-based strategy application.&#xD;
&#xD;
      In the countries which are expected to benefit from the strategy most this would mean&#xD;
      offering eradication treatment to the majority of population, e.g. in Latvia this would&#xD;
      require antibiotic treatment to 79% of population9, and would change the current status of&#xD;
      low antibiotic consumption country to an average consumption country. This could potentially&#xD;
      result in adverse consequences unrelated to H.pylori.&#xD;
&#xD;
      In a country with low H.pylori resistance to clarithromycin (such as Latvia), the recommended&#xD;
      H.pylori 1st-line standard eradication regimen would consist of clarithromycin in combination&#xD;
      to either amoxicillin or metronidazole, and a proton-pump inhibitor; the duration would be at&#xD;
      least 10 days10. Areas with higher H.pylori resistance to clarithromycin would require more&#xD;
      aggressive treatment modalities, e.g. by including levofloxacin to the regimen. The potential&#xD;
      adverse events caused by such therapies to microbiome are insufficiently studied; the expert&#xD;
      opinion that are developing guidelines is generally limited to the consideration that 1-2&#xD;
      week single-time antibiotic treatment would be a minor and fully reversible intervention upon&#xD;
      microbiome since according to the available statistic in many countries the average&#xD;
      antibiotic intake rates one or several treatments per year in a subject.&#xD;
&#xD;
      However, from the limited data available, there is a clear message that even one-week&#xD;
      treatment with macrolides (clarithromycin, azithromycin) is increasing the resistance of&#xD;
      macrolide-resistant S.pneumoniae in pharynx in healthy volunteers; this difference was&#xD;
      statistically significant within a period of 180 days11.&#xD;
&#xD;
      Thus the aim of this project proposal is to evaluate the long term effects of H.pylori&#xD;
      eradication on Gastro intestinal tract (GIT) microbiome, evaluate its effects on abundance&#xD;
      and prevalence of extended-spectrum beta-lactamases (ESBL) coding genes and develop cost&#xD;
      effective ESBL screening test prototype. To reach this goal during within the scope of this&#xD;
      project fecal samples will be collected of patients that are undergoing the eradication&#xD;
      therapy at two time points: before the start eradication and one year after the final&#xD;
      treatment. In order to decrease the number of feces samples that patients shall have to&#xD;
      acquire and standardize the sampling procedure, participants should explore the possibility&#xD;
      to employ fecal occult blood test containers. Since there are no conclusively positive&#xD;
      reports on employment of these devices in such analyses within the scope of this research&#xD;
      participants shall also develop an appropriate DNA extraction methodology. Further, employing&#xD;
      Next generation sequencing based analyses participants shall determine the microbial&#xD;
      community composition within each sample and through comparison of data from each time point&#xD;
      participants should be able to estimate the long term effects of eradication therapy.&#xD;
      Following this analysis participants should perform the identification of ESBL repertoire&#xD;
      within each sample and also evaluation their abundances abundance. Similarly as in the case&#xD;
      of community analysis the comparison of both time points shall allow to estimate the effects&#xD;
      of eradication therapy. Following the acquisition of the data participants shall outsource&#xD;
      the creation of ESBL screening test prototype, which shall be based on employment micro-bead&#xD;
      technology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">July 29, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">October 29, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Comparison between intervention groups and the group without intervention will be made</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Active treatment will be provided unmasked in the treatment groups</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of various H.pylori eradication regimens upon the gut microbiome</measure>
    <time_frame>6-36 months between the initial and the follow-up sample</time_frame>
    <description>Gut microbiome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effects of various H.pylori eradication regimens upon adverse events in short term</measure>
    <time_frame>21-28 days following the expected starting data of the treatmennt</time_frame>
    <description>Telephone interview following eradication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of various H.pylori eradication regimens</measure>
    <time_frame>1-12 months following eradication therapy</time_frame>
    <description>Effectiveness of H.pylori eradication will be evaluated by 13C urea breath test (UBT). Initially, 14 day clarythromycin-containing triple therapy will be compared to 14-day amoxicillin and bismuth containing therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of various H.pylori eradication regimens upon the pharyngeal microbiome</measure>
    <time_frame>6-36 months between the initial and the follow-up sample</time_frame>
    <description>Pharyngeal microbiome before and after H.pylori eradication will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of various H.pylori eradication regimens upon long-lasting adverse events</measure>
    <time_frame>6 months - 10 years following eradication</time_frame>
    <description>Adverse evens like symptoms of gastro-esophageal reflux disease, obesity, functional bowel disease will be addressed</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">900</enrollment>
  <condition>Human Microbiome</condition>
  <arm_group>
    <arm_group_label>H.pylori Eradication index</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Microbiome diversity detection in Participants Positive for H.pylori and undergoing Eradication therapy with Clarythromycin-containing eradication therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Microbiome diversity detection in Participants Without H.pylori Eradication therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>H.pylori Eradication comparative</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Microbiome diversity detection in Participants Positive for H.pylori and undergoing Eradication therapy with high dose Amoxicillin and bismuth containing eradication therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Microbiome Diversity detection</intervention_name>
    <description>detection of microbiome composition and detection of specific mutations in genes conferring resistance to antibiotics</description>
    <arm_group_label>H.pylori Eradication comparative</arm_group_label>
    <arm_group_label>H.pylori Eradication index</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals with established H.pylori infection&#xD;
&#xD;
          -  Individuals in whom H.pylori eradication therapy is indicated according to the&#xD;
             international or national recommendations&#xD;
&#xD;
          -  Individuals who agree to undergo H.pylori eradication therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severely sick patients&#xD;
&#xD;
          -  Individuals in whom H.pylori eradication therapy is contra-indicated due to any&#xD;
             reasons&#xD;
&#xD;
          -  Individuals unable or unwilling to provide a sample for microbiome testing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Latvia</name>
      <address>
        <city>Riga</city>
        <zip>LV 1586</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Latvia</country>
  </location_countries>
  <reference>
    <citation>Herrero R, Parsonnet J, Greenberg ER. Prevention of gastric cancer. JAMA. 2014 Sep 24;312(12):1197-8. doi: 10.1001/jama.2014.10498. No abstract available.</citation>
    <PMID>25247512</PMID>
  </reference>
  <reference>
    <citation>Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241. No abstract available.</citation>
    <PMID>7715068</PMID>
  </reference>
  <reference>
    <citation>IARC, Monographs on the evaluation of carcinogenic risks to humans, volume 100. A review of carcinogen - Part B: biological agents. 2011, Lyon: International Agency for Research on Cancer.</citation>
  </reference>
  <reference>
    <citation>Lee YC, Chen TH, Chiu HM, Shun CT, Chiang H, Liu TY, Wu MS, Lin JT. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013 May;62(5):676-82. doi: 10.1136/gutjnl-2012-302240. Epub 2012 Jun 14.</citation>
    <PMID>22698649</PMID>
  </reference>
  <reference>
    <citation>Areia M, Carvalho R, Cadime AT, Rocha Goncalves F, Dinis-Ribeiro M. Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies. Helicobacter. 2013 Oct;18(5):325-37. doi: 10.1111/hel.12050. Epub 2013 Apr 9.</citation>
    <PMID>23566268</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>24182612</PMID>
  </reference>
  <reference>
    <citation>Moayyedi, P., Feasibility and cost effectiveness of population-based H. pylori eradication, in In: IARC Helicobacter pylori Working Group. Helicobacter pylori Eradication as a Strategy for Preventing Gastric Cancer. Lyon, France: International Agency for Research on Cancer (IARC Working Group Reports, No. 8); pp. 174-180</citation>
  </reference>
  <reference>
    <citation>Leja M, Cine E, Rudzite D, Vilkoite I, Huttunen T, Daugule I, Rumba-Rozenfelde I, Pimanov S, Liepniece-Karele I, Pahomova J, Purmalis K, Eglitis J, Pirags V, Dzerve V, Erglis A. Prevalence of Helicobacter pylori infection and atrophic gastritis in Latvia. Eur J Gastroenterol Hepatol. 2012 Dec;24(12):1410-7. doi: 10.1097/MEG.0b013e3283583ca5.</citation>
    <PMID>23114744</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>22491499</PMID>
  </reference>
  <reference>
    <citation>Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet. 2007 Feb 10;369(9560):482-90. doi: 10.1016/S0140-6736(07)60235-9.</citation>
    <PMID>17292768</PMID>
  </reference>
  <results_reference>
    <citation>Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P; faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015 Sep;64(9):1353-67. doi: 10.1136/gutjnl-2015-309252. Epub 2015 Jul 17.</citation>
    <PMID>26187502</PMID>
  </results_reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>August 20, 2018</last_update_submitted>
  <last_update_submitted_qc>August 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Helicobacter pylori</keyword>
  <keyword>Eradication</keyword>
  <keyword>Microbiome</keyword>
  <keyword>ESBL</keyword>
  <keyword>GIT</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03231332
org study id: 1.1.1.1/16/A/272
nct id: NCT03231332
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this Project is, within the scope of industrial research, to evaluate the long
      term effects of H.pylori eradication on microbiome (gut microbiome, upper respiratory tract
      microbiome) and lasting adverse events. In addition, the project aims to evaluate its effects
      on abundance and prevalence of extended-spectrum beta-lactamases coding genes and develop
      cost effective ESBL screening test prototype.
The current international guidelines and expert working groups are encouraging
      "search-and-treat" strategy for H.pylori to prevent gastric cancer1, 2. The highest yield of
      this approach is expected in countries with high incidence of gastric cancer and high
      prevalence of H.pylori infection. This approach will be further supported by the Maastricht V
      European guidelines (manuscript in preparation). The rationale for this approach is that 1-2%
      of the infected individuals are developing gastric cancer; the International Agency for
      Research on Cancer has classified H.pylori infection as Class I carcinogen3, 4. A study in
      Matsu island with high gastric cancer risk has suggested that gastric cancer incidence can be
      decreased by 25% by such strategy5; the limitations, however, include lack of the control
      group.

      Three recent meta-analysis have confirmed the cost-effectiveness of such approach6-8; of
      course, those are based on the limited currently available data on potential risks caused by
      population-based strategy application.

      In the countries which are expected to benefit from the strategy most this would mean
      offering eradication treatment to the majority of population, e.g. in Latvia this would
      require antibiotic treatment to 79% of population9, and would change the current status of
      low antibiotic consumption country to an average consumption country. This could potentially
      result in adverse consequences unrelated to H.pylori.

      In a country with low H.pylori resistance to clarithromycin (such as Latvia), the recommended
      H.pylori 1st-line standard eradication regimen would consist of clarithromycin in combination
      to either amoxicillin or metronidazole, and a proton-pump inhibitor; the duration would be at
      least 10 days10. Areas with higher H.pylori resistance to clarithromycin would require more
      aggressive treatment modalities, e.g. by including levofloxacin to the regimen. The potential
      adverse events caused by such therapies to microbiome are insufficiently studied; the expert
      opinion that are developing guidelines is generally limited to the consideration that 1-2
      week single-time antibiotic treatment would be a minor and fully reversible intervention upon
      microbiome since according to the available statistic in many countries the average
      antibiotic intake rates one or several treatments per year in a subject.

      However, from the limited data available, there is a clear message that even one-week
      treatment with macrolides (clarithromycin, azithromycin) is increasing the resistance of
      macrolide-resistant S.pneumoniae in pharynx in healthy volunteers; this difference was
      statistically significant within a period of 180 days11.

      Thus the aim of this project proposal is to evaluate the long term effects of H.pylori
      eradication on Gastro intestinal tract (GIT) microbiome, evaluate its effects on abundance
      and prevalence of extended-spectrum beta-lactamases (ESBL) coding genes and develop cost
      effective ESBL screening test prototype. To reach this goal during within the scope of this
      project fecal samples will be collected of patients that are undergoing the eradication
      therapy at two time points: before the start eradication and one year after the final
      treatment. In order to decrease the number of feces samples that patients shall have to
      acquire and standardize the sampling procedure, participants should explore the possibility
      to employ fecal occult blood test containers. Since there are no conclusively positive
      reports on employment of these devices in such analyses within the scope of this research
      participants shall also develop an appropriate DNA extraction methodology. Further, employing
      Next generation sequencing based analyses participants shall determine the microbial
      community composition within each sample and through comparison of data from each time point
      participants should be able to estimate the long term effects of eradication therapy.
      Following this analysis participants should perform the identification of ESBL repertoire
      within each sample and also evaluation their abundances abundance. Similarly as in the case
      of community analysis the comparison of both time points shall allow to estimate the effects
      of eradication therapy. Following the acquisition of the data participants shall outsource
      the creation of ESBL screening test prototype, which shall be based on employment micro-bead
      technology.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Comparison between intervention groups and the group without intervention will be made
primary purpose: Treatment
masking: None (Open Label)
masking description: Active treatment will be provided unmasked in the treatment groups
measure: Effects of various H.pylori eradication regimens upon the gut microbiome
time frame: 6-36 months between the initial and the follow-up sample
description: Gut microbiome
measure: Effects of various H.pylori eradication regimens upon adverse events in short term
time frame: 21-28 days following the expected starting data of the treatmennt
description: Telephone interview following eradication
measure: Effectiveness of various H.pylori eradication regimens
time frame: 1-12 months following eradication therapy
description: Effectiveness of H.pylori eradication will be evaluated by 13C urea breath test (UBT). Initially, 14 day clarythromycin-containing triple therapy will be compared to 14-day amoxicillin and bismuth containing therapy
measure: Effects of various H.pylori eradication regimens upon the pharyngeal microbiome
time frame: 6-36 months between the initial and the follow-up sample
description: Pharyngeal microbiome before and after H.pylori eradication will be compared
measure: Effects of various H.pylori eradication regimens upon long-lasting adverse events
time frame: 6 months - 10 years following eradication
description: Adverse evens like symptoms of gastro-esophageal reflux disease, obesity, functional bowel disease will be addressed
arm group label: H.pylori Eradication index
arm group type: Experimental
description: Microbiome diversity detection in Participants Positive for H.pylori and undergoing Eradication therapy with Clarythromycin-containing eradication therapy
arm group label: Control
arm group type: No Intervention
description: Microbiome diversity detection in Participants Without H.pylori Eradication therapy
arm group label: H.pylori Eradication comparative
arm group type: Active Comparator
description: Microbiome diversity detection in Participants Positive for H.pylori and undergoing Eradication therapy with high dose Amoxicillin and bismuth containing eradication therapy
intervention type: Other
intervention name: Microbiome Diversity detection
description: detection of microbiome composition and detection of specific mutations in genes conferring resistance to antibiotics
arm group label: H.pylori Eradication comparative
arm group label: H.pylori Eradication index
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Latvia
citation: Herrero R, Parsonnet J, Greenberg ER. Prevention of gastric cancer. JAMA. 2014 Sep 24;312(12):1197-8. doi: 10.1001/jama.2014.10498. No abstract available.
PMID: 25247512
citation: Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241. No abstract available.
PMID: 7715068
citation: IARC, Monographs on the evaluation of carcinogenic risks to humans, volume 100. A review of carcinogen - Part B: biological agents. 2011, Lyon: International Agency for Research on Cancer.
citation: Lee YC, Chen TH, Chiu HM, Shun CT, Chiang H, Liu TY, Wu MS, Lin JT. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013 May;62(5):676-82. doi: 10.1136/gutjnl-2012-302240. Epub 2012 Jun 14.
PMID: 22698649
citation: Areia M, Carvalho R, Cadime AT, Rocha Goncalves F, Dinis-Ribeiro M. Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies. Helicobacter. 2013 Oct;18(5):325-37. doi: 10.1111/hel.12050. Epub 2013 Apr 9.
PMID: 23566268
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.
PMID: 24182612
citation: Moayyedi, P., Feasibility and cost effectiveness of population-based H. pylori eradication, in In: IARC Helicobacter pylori Working Group. Helicobacter pylori Eradication as a Strategy for Preventing Gastric Cancer. Lyon, France: International Agency for Research on Cancer (IARC Working Group Reports, No. 8); pp. 174-180
citation: Leja M, Cine E, Rudzite D, Vilkoite I, Huttunen T, Daugule I, Rumba-Rozenfelde I, Pimanov S, Liepniece-Karele I, Pahomova J, Purmalis K, Eglitis J, Pirags V, Dzerve V, Erglis A. Prevalence of Helicobacter pylori infection and atrophic gastritis in Latvia. Eur J Gastroenterol Hepatol. 2012 Dec;24(12):1410-7. doi: 10.1097/MEG.0b013e3283583ca5.
PMID: 23114744
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.
PMID: 22491499
citation: Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet. 2007 Feb 10;369(9560):482-90. doi: 10.1016/S0140-6736(07)60235-9.
PMID: 17292768
citation: Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P; faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015 Sep;64(9):1353-67. doi: 10.1136/gutjnl-2015-309252. Epub 2015 Jul 17.
PMID: 26187502
responsible party type: Sponsor