<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/NCT03299725</url>
  </required_header>
  <id_info>
    <org_study_id>CBS-EAM 10d</org_study_id>
    <nct_id>NCT03299725</nct_id>
  </id_info>
  <brief_title>Bismuth Based Quadruple Therapy 10 Days in Children</brief_title>
  <official_title>A Prospective Open-label Study on Efficacy and Tolerability of Colloidal Bismuth Sub-citrate as Adjunctive Therapy to a Combination of Esomeprazole, Amoxicillin and Metronidazole for 10 Days for Helicobacter Pylori Elimination in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen Fabiola Children's University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Queen Fabiola Children's University Hospital</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>
      Helicobacter pylori infection causes chronic gastritis, peptic ulcer disease and is involved&#xD;
      in the development of gastric cancer.&#xD;
&#xD;
      Current accepted strategies to eliminate the infection in children are a 10 days sequential&#xD;
      treatment (proton pump inhibitor + amoxicillin 5 days followed by proton pump inhibitor +&#xD;
      metronidazole + clarithromycin 5 days) or a triple therapy 14 days (proton pump inhibitor +&#xD;
      amoxicillin + clarithromycin or metronidazole).&#xD;
&#xD;
      However, there is a concern due to the growing resistance of Helicobacter pylori strains to&#xD;
      antibiotics, especially clarithromycin, and the decreased efficacy of first line treatment&#xD;
      regimens to satisfactorily eliminate the infection in children.&#xD;
&#xD;
      Recent data show that combinations using bismuth salts must be considered in adults. Indeed,&#xD;
      the efficacy of a 10 days of quadruple therapy with omeprazole plus a single three-in-one&#xD;
      capsule containing bismuth subcitrate, metronidazole and tetracycline was shown to be highly&#xD;
      superior to the standard triple therapy combining omeprazole, amoxicillin, and clarithromycin&#xD;
      without related severe adverse events.&#xD;
&#xD;
      The possibility of re-using bismuth salts on a more regular basis in pediatrics is being&#xD;
      restudied through a monocentric, prospective, open label, single arm clinical trial to assess&#xD;
      the safety and efficacy of a 10 days colloidal bismuth sub-citrate as an adjunctive therapy&#xD;
      in combination with esomeprazole, amoxicillin and metronidazole in children aged 6-17 years,&#xD;
      infected by Helicobacter pylori.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 24, 2017</start_date>
  <completion_date type="Anticipated">November 2019</completion_date>
  <primary_completion_date type="Anticipated">November 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>13C-urea breath test</measure>
    <time_frame>Week 10</time_frame>
    <description>Ratio of 13C/12C, expressed as delta 13C in pro mil, and compared with PeeDee Belemnite calcium carbonate standard</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse event</measure>
    <time_frame>Up to 10 weeks after start of study treatment</time_frame>
    <description>Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to the study treatment</measure>
    <time_frame>week 2</time_frame>
    <description>Adherence reported by patient on a diary card and study drug accountability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intestinal microbiome analysis</measure>
    <time_frame>Week 0</time_frame>
    <description>Qualitative description</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intestinal microbiome analysis</measure>
    <time_frame>Week 10</time_frame>
    <description>Changes in the relative phylum-level abundance in the stools, based on 16S rRNA classification, between week 0 and week 10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of antimicrobial resistance on the success rate</measure>
    <time_frame>Week 10</time_frame>
    <description>Qualitative description</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Helicobacter Pylori Infection</condition>
  <arm_group>
    <arm_group_label>Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>colloidal bismuth sub-citrate</intervention_name>
    <description>colloidal bismuth sub-citrate administered as an adjunctive therapy in combination with esomeprazole, amoxicillin and metronidazole</description>
    <arm_group_label>Treatment arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Paediatric subjects aged 6 to 17 years of either gender&#xD;
&#xD;
          -  Body weight ≥ 20kg.&#xD;
&#xD;
          -  Helicobacter pylori gastritis confirmed by positive histology and culture with&#xD;
             antimicrobial susceptibility testing.&#xD;
&#xD;
          -  Antral and corpus biopsies must have been taken for histology and culture during an&#xD;
             upper GI endoscopy performed for chronic or recurrent pain in the epigastric region&#xD;
             with epigastric tenderness at physical examination.&#xD;
&#xD;
          -  Subject able to swallow tablets.&#xD;
&#xD;
          -  All girls of child-bearing potential must have a negative urine pregnancy test at&#xD;
             Visit 1. If sexually active, girls of child-bearing potential and boys whose partner&#xD;
             is of child-bearing potential agree to use highly effective method of birth control&#xD;
             during the trial.&#xD;
&#xD;
          -  In the Investigator's opinion, patient is willing and able to comply with all trial&#xD;
             requirements specified in this protocol.&#xD;
&#xD;
          -  Willing to allow his or her General Practitioner and consultant, if appropriate, to be&#xD;
             notified of participation in the trial.&#xD;
&#xD;
          -  Subjects (or their legally-acceptable representatives) must have signed an informed&#xD;
             consent document indicating that they understand the purpose of and procedures&#xD;
             required for the study and are willing to participate in the study. Assent is also&#xD;
             required of children capable of understanding the nature of the study (typically older&#xD;
             than 11 years of age).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female participant who is pregnant, lactating or planning pregnancy during the course&#xD;
             of the trial.&#xD;
&#xD;
          -  Have a history of significant renal or hepatic impairment.&#xD;
&#xD;
          -  Have an erosive esophagitis or peptic ulcer disease in the gastric or the duodenal&#xD;
             mucosa showed during the upper GI endoscopy.&#xD;
&#xD;
          -  Have received proton pump inhibitors within 2 weeks prior to first administration of&#xD;
             study agent.&#xD;
&#xD;
          -  Have received any antimicrobial agent within 4 weeks prior to first administration of&#xD;
             study agent.&#xD;
&#xD;
          -  Require routine use (≥ 2 times per week) of non-steroidal anti-inflammatory drug&#xD;
             (NSAID).&#xD;
&#xD;
          -  Are under any immunosuppressive agent.&#xD;
&#xD;
          -  Are under oral or IV steroids&#xD;
&#xD;
          -  Have a scheduled elective surgery or any procedures requiring general anaesthesia&#xD;
             during the trial.&#xD;
&#xD;
          -  Have known allergies or a known hypersensitivity to any Study Drugs or their&#xD;
             excipients (refer to Study Drugs SmPCs).&#xD;
&#xD;
          -  Contraindication for any of the Study Drugs (refer to Study Drugs SmPCs).&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would compromise the&#xD;
             well-being of the subject or the study or prevent the subject from meeting or&#xD;
             performing study requirements.&#xD;
&#xD;
          -  Subjects who are participating or have participated in another study with an IMP in&#xD;
             the past 12 weeks.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Abdallah Kanfaoui, MD</last_name>
    <role>Study Director</role>
    <affiliation>Queen Fabiola Children's University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Samy Cadranel, MDPhD</last_name>
    <phone>0032 2 477 32 16</phone>
    <email>samy.cadranel@huderf.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Patrick Bontems, MDPhD</last_name>
    <phone>0032 2 477 32 16</phone>
    <email>patrick.bontems@huderf.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Universitaire Des Enfants Reine Fabiola</name>
      <address>
        <city>Brussels</city>
        <zip>1020</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Samy Cadranel, MDPhD</last_name>
      <phone>003224773216</phone>
      <email>samy.cadranel@huderf.be</email>
    </contact>
    <investigator>
      <last_name>Samy Cadranel, MDPhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>February 14, 2018</last_update_submitted>
  <last_update_submitted_qc>February 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bismuth</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03299725
org study id: CBS-EAM 10d
nct id: NCT03299725
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Helicobacter pylori infection causes chronic gastritis, peptic ulcer disease and is involved
      in the development of gastric cancer.

      Current accepted strategies to eliminate the infection in children are a 10 days sequential
      treatment (proton pump inhibitor + amoxicillin 5 days followed by proton pump inhibitor +
      metronidazole + clarithromycin 5 days) or a triple therapy 14 days (proton pump inhibitor +
      amoxicillin + clarithromycin or metronidazole).

      However, there is a concern due to the growing resistance of Helicobacter pylori strains to
      antibiotics, especially clarithromycin, and the decreased efficacy of first line treatment
      regimens to satisfactorily eliminate the infection in children.

      Recent data show that combinations using bismuth salts must be considered in adults. Indeed,
      the efficacy of a 10 days of quadruple therapy with omeprazole plus a single three-in-one
      capsule containing bismuth subcitrate, metronidazole and tetracycline was shown to be highly
      superior to the standard triple therapy combining omeprazole, amoxicillin, and clarithromycin
      without related severe adverse events.

      The possibility of re-using bismuth salts on a more regular basis in pediatrics is being
      restudied through a monocentric, prospective, open label, single arm clinical trial to assess
      the safety and efficacy of a 10 days colloidal bismuth sub-citrate as an adjunctive therapy
      in combination with esomeprazole, amoxicillin and metronidazole in children aged 6-17 years,
      infected by Helicobacter pylori.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 13C-urea breath test
time frame: Week 10
description: Ratio of 13C/12C, expressed as delta 13C in pro mil, and compared with PeeDee Belemnite calcium carbonate standard
measure: Incidence of treatment-emergent adverse event
time frame: Up to 10 weeks after start of study treatment
description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
measure: Adherence to the study treatment
time frame: week 2
description: Adherence reported by patient on a diary card and study drug accountability
measure: Intestinal microbiome analysis
time frame: Week 0
description: Qualitative description
measure: Intestinal microbiome analysis
time frame: Week 10
description: Changes in the relative phylum-level abundance in the stools, based on 16S rRNA classification, between week 0 and week 10
measure: Effect of antimicrobial resistance on the success rate
time frame: Week 10
description: Qualitative description
arm group label: Treatment arm
arm group type: Experimental
intervention type: Drug
intervention name: colloidal bismuth sub-citrate
description: colloidal bismuth sub-citrate administered as an adjunctive therapy in combination with esomeprazole, amoxicillin and metronidazole
arm group label: Treatment arm
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
last name: Abdallah Kanfaoui, MD
role: Study Director
affiliation: Queen Fabiola Children's University Hospital
last name: Samy Cadranel, MDPhD
phone: 0032 2 477 32 16
email: samy.cadranel@huderf.be
last name: Patrick Bontems, MDPhD
phone: 0032 2 477 32 16
email: patrick.bontems@huderf.be
facility: 
status: Recruiting
contact: 
investigator: 
country: Belgium
responsible party type: Sponsor
mesh term: Bismuth
sharing ipd: No