<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/NCT03802318</url>
  </required_header>
  <id_info>
    <org_study_id>201801792A3</org_study_id>
    <nct_id>NCT03802318</nct_id>
  </id_info>
  <brief_title>Daily Four Times or Two Times Usage of PPI and Amoxicillin for the First or Second Line H. Pylori Eradication</brief_title>
  <official_title>A Comparison Study of Helicobacter Pylori Eradication Rates Between Daily Four Times and Daily Two Times Usage of Proton Pump Inhibitor and Amoxicillin for the First Line and the Second Line Eradication Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The hypothesis and plan of the current study are:&#xD;
&#xD;
        1. One induction phase of high dose PPI before eradication will increase intragastric pH&#xD;
           and induce H. pylori into an active replicative status. Active replicative status will&#xD;
           enhance the bactericidal effect of amoxicillin. Rabeprazole (20 mg) four times per day&#xD;
           (qid) for 3 days will be used for induction in this study.&#xD;
&#xD;
        2. High dose PPI will provide adequate plasma concentration irrespective of the CYP2C19&#xD;
           genotype of the population. Here rabeprazole (20 mg) qid will be applied as high dose&#xD;
           PPI.&#xD;
&#xD;
        3. High frequent amoxicillin usage (500 mg, qid) will maintain plasma concentration above&#xD;
           the MIC. Amoxicillin (500 mg) qid will be described for total 14 days.&#xD;
&#xD;
        4. In the rescue therapy, add levofloxacin on high dose dual therapy will increase the&#xD;
           eradication rate than single high dose dual therapy. A combination of levofloxacin and&#xD;
           high dose dual therapy will also have a better eradication rate than the common used&#xD;
           levofloxacin based triple therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study aims to evaluate:&#xD;
&#xD;
        1. the first line H. pylori eradication rate of high dose dual therapy with 14 days&#xD;
           rabeprazole 20 mg qid, plus amoxicillin 500 mg qid (HDDT group) comparing to the&#xD;
           clarithromycin-based triple therapy with 14 days clarithromycin 500 mg bid, amoxicillin&#xD;
           1000mg bid , and rabeprazole 20mg bid (CATT group).&#xD;
&#xD;
        2. the eradication efficacy in rescue therapy of a levofloxacin-based triple therapy with&#xD;
           14 days levofloxacin 500 mg qd, amoxicillin 500 mg qid and rabeprazole 20 mg qid (LHDT&#xD;
           group) comparing to the common levofloxacin-based triple therapy with 14 days&#xD;
           levofloxacin 500 mg qd, amoxicillin 1000mg bid and rabeprazole 20 mg (LATT group).&#xD;
&#xD;
      Material and Methods Patients and study design This is a prospective, randomized, open-label&#xD;
      trial. The patients diagnosed with H. pylori infection will be enrolled from Jan 2019 to Dec&#xD;
      2020 in Keelung Chang-Gung Memorial hospital. The source of subjects may include (1)&#xD;
      community participants who obtain a positive result of urea breath test (UBT) from the&#xD;
      checkup screening (2) hospital patients who obtain a positive result of H. pylori infection&#xD;
      by esophagogastroduodenoscopy (EGD). Exclusion criteria include age less than 20 years,&#xD;
      pregnancy or nursing, serious concomitant illness, malignant tumors, history of&#xD;
      hypersensitivity to study drugs, active ulcer bleeding, previous gastric surgeries, and&#xD;
      taking PPIs within two weeks or antibiotics within one month before study. Patients without&#xD;
      previous H. pylori eradication therapy are invited to receive the first-line regimens,&#xD;
      whereas patients who have previously received H. pylori eradication therapy are invited to&#xD;
      receive rescue regimens.&#xD;
&#xD;
      Hospital patients are asked to receive five endoscopic biopsy specimens (3 from gastric&#xD;
      antrum and 2 from body mucosa) for rapid urease test (RUT) and culture studies. The&#xD;
      definition of H. pylori infection is a positive finding from UBT, RUT or culture.&#xD;
&#xD;
      Diagnosis for H. pylori infection RUT Three specimens from endoscopic biopsy are used for the&#xD;
      RUT (HelicotecUT ® plus test; Strong Biotech Corporation, Taipei, Taiwan). The test result&#xD;
      will be read one hour later. A medium color change from yellowish to pink or red is recorded&#xD;
      as a positive finding for H. pylori.&#xD;
&#xD;
      Bacterial culture and antibiotic susceptibility test Two specimens are homogenized and&#xD;
      streaked onto an agar plate with selective medium. The plates are incubated at 37∘C under&#xD;
      microaerophilic conditions (5% O2, 10% CO2, 85% N2) for 3-7 days. H pylori is identified by&#xD;
      its characteristic biotyping. The primary isolates are subcultured for antibiotic&#xD;
      susceptibility tests as described previously [21]. The E test strips (AB Biodisk, Solna,&#xD;
      Sweden) are used for susceptibility testing. The resistance to antibiotics is according to&#xD;
      MIC values of &gt;0.5, ≥1, ≥8, and &gt;1 mg/L for amoxicillin, clarithromycin, tetracycline, and&#xD;
      levofloxacin, respectively [21].&#xD;
&#xD;
      Subjects should complete a standardized questionnaire and recorded symptoms and daily drug&#xD;
      consumption during the treatment period to evaluate compliance and tolerability.&#xD;
&#xD;
      All patients are asked to describe any adverse event (diarrhea, taste disturbance, nausea ⁄&#xD;
      vomiting, bloating, abdominal pain, constipation, headache and skin rash) during the period&#xD;
      when they are taking eradication drugs. The incidence of side effects is checked using a&#xD;
      standardized degree of interference with daily activities format, as follows: absent;&#xD;
      mild-not interfering; moderate-frequently interfering, but allowing treatment to be&#xD;
      completed; severe-requiring interruption of treatment [33].&#xD;
&#xD;
      Four weeks after treatment completion, H pylori eradication success will be determined by&#xD;
      13C-UBT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">January 2, 2019</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>H. pylori eradication rate</measure>
    <time_frame>2~3 months</time_frame>
    <description>Two to three months after eradication therapy, urea breath test will be performed. If the result of UBT is negative, it means successful eradication. If the result is positive, it means eradicaiton failure</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">530</enrollment>
  <condition>Helicobacter Pylori Infection</condition>
  <condition>Helicobacter Gastritis</condition>
  <condition>Helicobacter-Associated Pyloric Ulcer</condition>
  <arm_group>
    <arm_group_label>HDDT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>high dose PPI induction (oral rabeprazole 20mg qid) for 3 days, then 14 days combined with amoxicillin (regular dose, daily 2 g, 500mg qid) for high frequency dual therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CATT group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>conventional triple therapy 14 days (rabeprazole 20 mg bid, amoxicillin 1 g bid, clarithromycin 500 mg bid)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LHDT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>high dose PPI (oral rabeprazole 20mg qid) induction for 3 days, then Rabeprazole 20 mg qid, amoxicillin 500 mg qid, levofloxacin 500 mg qd for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LATT group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>levofloxacin base rescue therapy 14 days (rabeprazole 20 mg bid, amoxicillin 1 g bid, levofloxacin 500 mg qd)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rabeprazole</intervention_name>
    <description>Rabeprazole daily four time (Bid) or daily four times (Qid) Amoxicillin used daily two times (1000 mg bid) or daily four times (500 mg qid) apply in the first line or the second line H pylori eradication therapy</description>
    <arm_group_label>CATT group</arm_group_label>
    <arm_group_label>HDDT group</arm_group_label>
    <arm_group_label>LATT group</arm_group_label>
    <arm_group_label>LHDT group</arm_group_label>
    <other_name>Amoxicillin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The source of subjects may include (1) community participants who obtain a positive&#xD;
             result of urea breath test (UBT) from the checkup screening (2) hospital patients who&#xD;
             obtain a positive result of H. pylori infection by esophagogastroduodenoscopy (EGD).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exclusion criteria include age less than 20 years, pregnancy or nursing, serious&#xD;
             concomitant illness, malignant tumors, history of hypersensitivity to study drugs,&#xD;
             active ulcer bleeding, previous gastric surgeries, and taking PPIs within two weeks or&#xD;
             antibiotics within one month before study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming-Jui Hung, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Chang-Gung Memorial Hospital at Keelung</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chang-Gung memorial hospital at Keelung</name>
      <address>
        <city>Keelung</city>
        <zip>20401</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>January 11, 2019</last_update_submitted>
  <last_update_submitted_qc>January 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Li-Wei Chen</investigator_full_name>
    <investigator_title>chief, division of hepato-gastroenterology</investigator_title>
  </responsible_party>
  <keyword>Helicobacter pylori</keyword>
  <keyword>Proton pump inhibitor</keyword>
  <keyword>Amoxicillin</keyword>
  <keyword>Urea breath test</keyword>
  <keyword>Levofloxacin</keyword>
  <keyword>Clarithromycin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Rabeprazole</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03802318
org study id: 201801792A3
nct id: NCT03802318
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The hypothesis and plan of the current study are:

        1. One induction phase of high dose PPI before eradication will increase intragastric pH
           and induce H. pylori into an active replicative status. Active replicative status will
           enhance the bactericidal effect of amoxicillin. Rabeprazole (20 mg) four times per day
           (qid) for 3 days will be used for induction in this study.

        2. High dose PPI will provide adequate plasma concentration irrespective of the CYP2C19
           genotype of the population. Here rabeprazole (20 mg) qid will be applied as high dose
           PPI.

        3. High frequent amoxicillin usage (500 mg, qid) will maintain plasma concentration above
           the MIC. Amoxicillin (500 mg) qid will be described for total 14 days.

        4. In the rescue therapy, add levofloxacin on high dose dual therapy will increase the
           eradication rate than single high dose dual therapy. A combination of levofloxacin and
           high dose dual therapy will also have a better eradication rate than the common used
           levofloxacin based triple therapy.
This study aims to evaluate:

        1. the first line H. pylori eradication rate of high dose dual therapy with 14 days
           rabeprazole 20 mg qid, plus amoxicillin 500 mg qid (HDDT group) comparing to the
           clarithromycin-based triple therapy with 14 days clarithromycin 500 mg bid, amoxicillin
           1000mg bid , and rabeprazole 20mg bid (CATT group).

        2. the eradication efficacy in rescue therapy of a levofloxacin-based triple therapy with
           14 days levofloxacin 500 mg qd, amoxicillin 500 mg qid and rabeprazole 20 mg qid (LHDT
           group) comparing to the common levofloxacin-based triple therapy with 14 days
           levofloxacin 500 mg qd, amoxicillin 1000mg bid and rabeprazole 20 mg (LATT group).

      Material and Methods Patients and study design This is a prospective, randomized, open-label
      trial. The patients diagnosed with H. pylori infection will be enrolled from Jan 2019 to Dec
      2020 in Keelung Chang-Gung Memorial hospital. The source of subjects may include (1)
      community participants who obtain a positive result of urea breath test (UBT) from the
      checkup screening (2) hospital patients who obtain a positive result of H. pylori infection
      by esophagogastroduodenoscopy (EGD). Exclusion criteria include age less than 20 years,
      pregnancy or nursing, serious concomitant illness, malignant tumors, history of
      hypersensitivity to study drugs, active ulcer bleeding, previous gastric surgeries, and
      taking PPIs within two weeks or antibiotics within one month before study. Patients without
      previous H. pylori eradication therapy are invited to receive the first-line regimens,
      whereas patients who have previously received H. pylori eradication therapy are invited to
      receive rescue regimens.

      Hospital patients are asked to receive five endoscopic biopsy specimens (3 from gastric
      antrum and 2 from body mucosa) for rapid urease test (RUT) and culture studies. The
      definition of H. pylori infection is a positive finding from UBT, RUT or culture.

      Diagnosis for H. pylori infection RUT Three specimens from endoscopic biopsy are used for the
      RUT (HelicotecUT ® plus test; Strong Biotech Corporation, Taipei, Taiwan). The test result
      will be read one hour later. A medium color change from yellowish to pink or red is recorded
      as a positive finding for H. pylori.

      Bacterial culture and antibiotic susceptibility test Two specimens are homogenized and
      streaked onto an agar plate with selective medium. The plates are incubated at 37∘C under
      microaerophilic conditions (5% O2, 10% CO2, 85% N2) for 3-7 days. H pylori is identified by
      its characteristic biotyping. The primary isolates are subcultured for antibiotic
      susceptibility tests as described previously [21]. The E test strips (AB Biodisk, Solna,
      Sweden) are used for susceptibility testing. The resistance to antibiotics is according to
      MIC values of >0.5, ≥1, ≥8, and >1 mg/L for amoxicillin, clarithromycin, tetracycline, and
      levofloxacin, respectively [21].

      Subjects should complete a standardized questionnaire and recorded symptoms and daily drug
      consumption during the treatment period to evaluate compliance and tolerability.

      All patients are asked to describe any adverse event (diarrhea, taste disturbance, nausea ⁄
      vomiting, bloating, abdominal pain, constipation, headache and skin rash) during the period
      when they are taking eradication drugs. The incidence of side effects is checked using a
      standardized degree of interference with daily activities format, as follows: absent;
      mild-not interfering; moderate-frequently interfering, but allowing treatment to be
      completed; severe-requiring interruption of treatment [33].

      Four weeks after treatment completion, H pylori eradication success will be determined by
      13C-UBT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: H. pylori eradication rate
time frame: 2~3 months
description: Two to three months after eradication therapy, urea breath test will be performed. If the result of UBT is negative, it means successful eradication. If the result is positive, it means eradicaiton failure
arm group label: HDDT group
arm group type: Experimental
description: high dose PPI induction (oral rabeprazole 20mg qid) for 3 days, then 14 days combined with amoxicillin (regular dose, daily 2 g, 500mg qid) for high frequency dual therapy.
arm group label: CATT group
arm group type: Placebo Comparator
description: conventional triple therapy 14 days (rabeprazole 20 mg bid, amoxicillin 1 g bid, clarithromycin 500 mg bid)
arm group label: LHDT group
arm group type: Experimental
description: high dose PPI (oral rabeprazole 20mg qid) induction for 3 days, then Rabeprazole 20 mg qid, amoxicillin 500 mg qid, levofloxacin 500 mg qd for 14 days.
arm group label: LATT group
arm group type: Placebo Comparator
description: levofloxacin base rescue therapy 14 days (rabeprazole 20 mg bid, amoxicillin 1 g bid, levofloxacin 500 mg qd)
intervention type: Drug
intervention name: Rabeprazole
description: Rabeprazole daily four time (Bid) or daily four times (Qid) Amoxicillin used daily two times (1000 mg bid) or daily four times (500 mg qid) apply in the first line or the second line H pylori eradication therapy
arm group label: CATT group
arm group label: HDDT group
arm group label: LATT group
arm group label: LHDT group
other name: Amoxicillin
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ming-Jui Hung, PhD
role: Study Chair
affiliation: Chang-Gung Memorial Hospital at Keelung
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Chang Gung Memorial Hospital
investigator full name: Li-Wei Chen
investigator title: chief, division of hepato-gastroenterology
mesh term: Gastritis
mesh term: Amoxicillin
mesh term: Rabeprazole