<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/NCT03038009</url>
  </required_header>
  <id_info>
    <org_study_id>IISR-2016-101603</org_study_id>
    <nct_id>NCT03038009</nct_id>
  </id_info>
  <brief_title>Proton Pump Inhibitor Prevent Dual Antiplatelet Agents Induced Gastrointestinal Ulcer After Coronary Artery Bypass Graft</brief_title>
  <acronym>DACAB-GI-2</acronym>
  <official_title>Evaluation of the Efficacy and Safety of Different Duration of Proton Pump Inhibitor for Prevention of Upper Gastrointestinal Mucosal Injury in Patients Taking 12-month Dual Antiplatelet Therapy After Coronary Artery Bypass Graft Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ruijin Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether 12-month prophylactic treatment with&#xD;
      pantoprazole is superior to 1-month therapy without major cardiovascular events (MACE)&#xD;
      increased significantly, in prevention of dual antiplatelet therapy (DAPT)-induced upper&#xD;
      gastrointestinal (GI) mucosal injury after coronary artery bypass graft (CABG) surgery. The&#xD;
      potentially serious harm of DAPT on gastroduodenal mucosa will be assessed by&#xD;
      esophagogastroduodenoscopy (EGD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Endoscopic evaluation of gastroduodenal mucosal injury:&#xD;
&#xD;
      Based on the modified Lanza score, the new endoscopic evaluation system established in the&#xD;
      DACAB-GI-1 study includes 6 grades of mucosal injuries. Grade 0: normal mucosa; Grade 1:&#xD;
      erythema or petechiae only; Grade 2: 1 to 2 erosive lesions; Grade 3: 3 to 10 erosive&#xD;
      lesions; Grade 4: more than 10 erosive lesions or small ulcers (diameter: 3-5mm); Grade 5: an&#xD;
      ulcer is greater than 5 mm in diameter. Comprehensive results of gastroduodenal mucosal&#xD;
      injury will be marked as G0-5 (G: gastro) and D0-5 (D: duodeno) together. Mild injury was&#xD;
      defined as level II or less. Severe injury was defined from level III to V, which should be&#xD;
      treated with proton pump inhibitor (PPI) to decrease the risk of upper GI bleeding. The new&#xD;
      level system is as following: Level 0: G0D0; Level I: G1D0-1/G0D1; Level II: G2D0-2/G0-1D2;&#xD;
      Level III: G3D0-3/G0-2D3; Level IV: G4D0-4/G0-3D4; Level V: G5D0-5/G0-4D5.&#xD;
&#xD;
      Sample size justification:&#xD;
&#xD;
      Until now, no published data or reference is available for the efficacy of pantoprazole when&#xD;
      concomitant use with DAPT. The results from the preliminary study (DACAB-GI-1) showed that&#xD;
      the percentage of serious gastroduodenal mucosal lesions (Level III-V) in patients treated&#xD;
      with PPIs for 1, 3 and more than 6 months were 36.76%, 28.45% and 17.65%, respectively.&#xD;
      Therefore, the efficacy difference of pantoprazole is estimated to be 18% between 2 groups.&#xD;
      The average incidence of gastroduodenal mucosal injury is estimated to be 36% in the control&#xD;
      group (1-month therapy of pantoprazole), and the corresponding incidence in the experimental&#xD;
      group (12-month therapy of pantoprazole) is estimated to be 18%.&#xD;
&#xD;
      The determination of minimal sample size is as following: Group sample sizes of 93 in the&#xD;
      experimental group and 93 in the control group achieve 80% power to detect a difference&#xD;
      between the group proportions of -18%. The proportion in the experimental group is assumed to&#xD;
      be 36% under the null hypothesis and 18% under the alternative hypothesis. The proportion in&#xD;
      the control group is 36%. The test statistic used is Pearson Chi-Squared test. The&#xD;
      significance level of the test was targeted at 0.05. The significance level actually achieved&#xD;
      by this design is 0.0522. Considering 10% of the lost and/or drop-out rate, the final sample&#xD;
      size estimated will be 104 in the experimental group and control group, respectively. The&#xD;
      total sample size is no less than 208.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    A new registration has been submitted due to a redesign of the study protocol.&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 2018</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2020</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative incidence of gastroduodenal erosions and ulcers.</measure>
    <time_frame>up to 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of gastroduodenal erosions and ulcers.</measure>
    <time_frame>up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of upper GI major bleeding according to TIMI criteria.</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of upper GI minor bleeding according to TIMI criteria</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of major cardiovascular events (MACE, composite of cardiovascular death, myocardial infarctions, or stroke).</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Safety Issue: Yes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of grafts failure.</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Safety Issue: Yes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Gastric Ulcer Induced by Antiplatelet Agent</condition>
  <condition>Ulcer of the Gastrointestinal Tract</condition>
  <condition>Proton Pump Inhibitor</condition>
  <arm_group>
    <arm_group_label>One-month therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pantoprazole, 40mg, tablet, oral, once daily for 1 month.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Twelve-month therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pantoprazole, 40mg, tablet, oral, once daily for 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pantoprazole</intervention_name>
    <description>Pantoprazole (40mg qd) will be concomitant used with DAPT</description>
    <arm_group_label>One-month therapy</arm_group_label>
    <arm_group_label>Twelve-month therapy</arm_group_label>
    <other_name>PANTOLOC, Tablet from Takeda Pharmaceutical Company Limited</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Each patient should meet all of the inclusion criteria and none of the exclusion criteria&#xD;
        for this study:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures.&#xD;
&#xD;
          2. CABG surgery is performed for the first time.&#xD;
&#xD;
          3. Need 12-month DAPT (aspirin 100mg qd plus clopidogrel 75mg qd or aspirin 100mg qd plus&#xD;
             ticagrelor 90mg bid depending on randomisation) immediately following CABG surgery&#xD;
             according to the guideline.&#xD;
&#xD;
          4. Concomitant use of pantoprazole (40mg qd) for at least 1 moth following CABG surgery.&#xD;
&#xD;
          5. Willing to undergo EGD twice a year (at 6th and 12th month following CABG surgery,&#xD;
             respectively).&#xD;
&#xD;
          6. Willing to undergo 13C-UBT prior to CABG surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients should not enter the study if any of the following exclusion criteria are&#xD;
        fulfilled.&#xD;
&#xD;
          1. History of previous active peptic ulcer within 3 months prior to enrollment.&#xD;
&#xD;
          2. Planned use of PPI to treat gastric-acid associated diseases (e.g. gastroesophageal&#xD;
             reflux disease, GERD)&#xD;
&#xD;
          3. Contraindications for aspirin, clopidogrel, ticagrelor and pantoprazole use (e.g.&#xD;
             known allergy)&#xD;
&#xD;
          4. Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4&#xD;
             (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices, that cannot&#xD;
             be stopped for the course of the study.&#xD;
&#xD;
               -  Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin,&#xD;
                  clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir,&#xD;
                  atazanavir&#xD;
&#xD;
               -  CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses&#xD;
                  &gt; 40mg daily or lovastatin at doses &gt; 40mg daily.&#xD;
&#xD;
          5. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin.&#xD;
&#xD;
          6. History of previous intracerebral bleeding at any time, GI bleeding within the past 3&#xD;
             months prior to enrollment, or major surgery within 30 days prior to enrollment.&#xD;
&#xD;
          7. Known moderate to severe liver disease (e.g. gastroesophageal varices, ascites and/ or&#xD;
             clinical signs of coagulopathy)&#xD;
&#xD;
          8. Renal failure requiring dialysis.&#xD;
&#xD;
          9. Women of child-bearing potential who are not willing to use a medically accepted&#xD;
             method of contraception that is considered reliable in the judgement of investigator&#xD;
             OR women who have a positive pregnancy test at enrolment or randomisation OR women who&#xD;
             are breasting-feeding.&#xD;
&#xD;
         10. Inability of patient to understand and/or comply with study procedures and/or follow&#xD;
             up, in the opinion of the investigator, OR any conditions that, in the opinion of the&#xD;
             investigator, many render the patient unable to complete the study.&#xD;
&#xD;
         11. Any condition which in the opinion of the investigator would make it unsafe or&#xD;
             unsuitable for the patient to participate in this study (eg, long-term concomitant&#xD;
             treatment with non-steroidal anti-inflammatory drugs [NSAIDs]), or any condition&#xD;
             outside the atherothrombotic study area with a life expectancy of less than 2 years&#xD;
             based on investigator's judgement.&#xD;
&#xD;
         12. Paticipation in another clinical study with an investigational product within 28 days&#xD;
             prior to enrolment or previous randomization to an investigational product in another&#xD;
             ongoing clinical study. Participation in any previous study with clopidogrel or&#xD;
             tigagrelor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lifen Yu, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ruijin Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ruijin Hospital, Shanghai Jiao Tong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>January 29, 2017</study_first_submitted>
  <study_first_submitted_qc>January 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>April 5, 2019</last_update_submitted>
  <last_update_submitted_qc>April 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Lifen YU</investigator_full_name>
    <investigator_title>Associate Professor, Department of Gastroenterology</investigator_title>
  </responsible_party>
  <keyword>Coronary Artery Bypass Graft</keyword>
  <keyword>Dual Antiplatelet Therapy</keyword>
  <keyword>Gastrointestinal</keyword>
  <keyword>Mucosal Injury</keyword>
  <keyword>Proton Pump Inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Ulcer</mesh_term>
    <mesh_term>Peptic Ulcer</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pantoprazole</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/NCT03038009
org study id: IISR-2016-101603
nct id: NCT03038009
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine whether 12-month prophylactic treatment with
      pantoprazole is superior to 1-month therapy without major cardiovascular events (MACE)
      increased significantly, in prevention of dual antiplatelet therapy (DAPT)-induced upper
      gastrointestinal (GI) mucosal injury after coronary artery bypass graft (CABG) surgery. The
      potentially serious harm of DAPT on gastroduodenal mucosa will be assessed by
      esophagogastroduodenoscopy (EGD).
Endoscopic evaluation of gastroduodenal mucosal injury:

      Based on the modified Lanza score, the new endoscopic evaluation system established in the
      DACAB-GI-1 study includes 6 grades of mucosal injuries. Grade 0: normal mucosa; Grade 1:
      erythema or petechiae only; Grade 2: 1 to 2 erosive lesions; Grade 3: 3 to 10 erosive
      lesions; Grade 4: more than 10 erosive lesions or small ulcers (diameter: 3-5mm); Grade 5: an
      ulcer is greater than 5 mm in diameter. Comprehensive results of gastroduodenal mucosal
      injury will be marked as G0-5 (G: gastro) and D0-5 (D: duodeno) together. Mild injury was
      defined as level II or less. Severe injury was defined from level III to V, which should be
      treated with proton pump inhibitor (PPI) to decrease the risk of upper GI bleeding. The new
      level system is as following: Level 0: G0D0; Level I: G1D0-1/G0D1; Level II: G2D0-2/G0-1D2;
      Level III: G3D0-3/G0-2D3; Level IV: G4D0-4/G0-3D4; Level V: G5D0-5/G0-4D5.

      Sample size justification:

      Until now, no published data or reference is available for the efficacy of pantoprazole when
      concomitant use with DAPT. The results from the preliminary study (DACAB-GI-1) showed that
      the percentage of serious gastroduodenal mucosal lesions (Level III-V) in patients treated
      with PPIs for 1, 3 and more than 6 months were 36.76%, 28.45% and 17.65%, respectively.
      Therefore, the efficacy difference of pantoprazole is estimated to be 18% between 2 groups.
      The average incidence of gastroduodenal mucosal injury is estimated to be 36% in the control
      group (1-month therapy of pantoprazole), and the corresponding incidence in the experimental
      group (12-month therapy of pantoprazole) is estimated to be 18%.

      The determination of minimal sample size is as following: Group sample sizes of 93 in the
      experimental group and 93 in the control group achieve 80% power to detect a difference
      between the group proportions of -18%. The proportion in the experimental group is assumed to
      be 36% under the null hypothesis and 18% under the alternative hypothesis. The proportion in
      the control group is 36%. The test statistic used is Pearson Chi-Squared test. The
      significance level of the test was targeted at 0.05. The significance level actually achieved
      by this design is 0.0522. Considering 10% of the lost and/or drop-out rate, the final sample
      size estimated will be 104 in the experimental group and control group, respectively. The
      total sample size is no less than 208.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Cumulative incidence of gastroduodenal erosions and ulcers.
time frame: up to 12 months
measure: Incidence of gastroduodenal erosions and ulcers.
time frame: up to 6 months
measure: Incidence of upper GI major bleeding according to TIMI criteria.
time frame: up to 12 months
measure: Incidence of upper GI minor bleeding according to TIMI criteria
time frame: up to 12 months
measure: Incidence of major cardiovascular events (MACE, composite of cardiovascular death, myocardial infarctions, or stroke).
time frame: up to 12 months
description: Safety Issue: Yes
measure: Incidence of grafts failure.
time frame: up to 12 months
description: Safety Issue: Yes
arm group label: One-month therapy
arm group type: Active Comparator
description: Pantoprazole, 40mg, tablet, oral, once daily for 1 month.
arm group label: Twelve-month therapy
arm group type: Experimental
description: Pantoprazole, 40mg, tablet, oral, once daily for 12 months.
intervention type: Drug
intervention name: Pantoprazole
description: Pantoprazole (40mg qd) will be concomitant used with DAPT
arm group label: One-month therapy
arm group label: Twelve-month therapy
other name: PANTOLOC, Tablet from Takeda Pharmaceutical Company Limited
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Lifen Yu, MD, Ph.D
role: Principal Investigator
affiliation: Ruijin Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Lifen YU
investigator title: Associate Professor, Department of Gastroenterology
mesh term: Stomach Ulcer
mesh term: Peptic Ulcer
mesh term: Ulcer
mesh term: Pantoprazole
sharing ipd: No