xml: <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/NCT05976594</url>
    </required_header>
    <id_info>
      <org_study_id>PRO-HE-004-2</org_study_id>
      <nct_id>NCT05976594</nct_id>
    </id_info>
    <brief_title>Long-term Effectiveness of a Recombinant Hepatitis E Vaccine</brief_title>
    <official_title>Long-term Effectiveness of a Recombinant Hepatitis E Vaccine: a Test-negative Design Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Xiamen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Dongtai Center for Disease Control and Prevention</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Dongtai Hospital of Traditional Chinese Medicine</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Dongtai People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Xiamen University</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>
        This test-negative study is designed to evaluate the long-term effectiveness of hepatitis E&#xD;
        vaccine (Hecolin®) and to explore the prevalence of rat hepatitis E in Dongtai City.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this negative test study, residual clinical serum will be collected from 13 hospitals in&#xD;
        Dongtai, if it was from patients born between 1941-1991 from 11 towns in Dongtai, who tested&#xD;
        positive for ALT levels higher than 2.5 times the upper limit of normal (ULN). Detection of&#xD;
        HEV IgM, IgG, antigen, RNA will be performed to diagnose hepatitis E (HE) in each individual.&#xD;
        In addition, HE vaccination history will be collect. All the information above will be used&#xD;
        to evaluate the long-term effectiveness of HE vaccine. Based on the study design, virological&#xD;
        and serological detection (IgM, IgG, antigen, and RNA) of hepatitis E virus species C (HEV-C)&#xD;
        will be performed to analyze the prevalence of rat hepatitis E infection in Dongtai.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 12, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">July 1, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Rate of hepatitis E infection</measure>
      <time_frame>Two months after sampling</time_frame>
      <description>In patients with ALT &gt; 2.5 ULN, HEV infection is diagnosed as positive when two of the following indicators are positive: (1) HEV-IgM; (2) Seroconversion or four-fold increase of HEV-IgG；(3) HEV-RNA; (4) HEV-antigen.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Rate of rat hepatitis E infection</measure>
      <time_frame>Two months after sampling</time_frame>
      <description>In patients with ALT &gt; 2.5 ULN, rat hepatitis E infection is diagnosed as positive when two of the following virologic or serological tests are positive: (1) IgM anti-HEV-C-; (2) IgG anti-HEV-C- seroconversion or four-fold increase；(3) HEV-C-RNA; (4) HEV-C-antigen.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">2900</enrollment>
    <condition>Hepatitis E</condition>
    <arm_group>
      <arm_group_label>HE group</arm_group_label>
      <description>Subjects who has been diagnosed as HE.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <description>Subjects who didn't meet the diagnosis criteria of HE.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>serology and virology detection of hepatitis E virus</intervention_name>
      <description>Serum will be tested for HEV serology and virology, including HEV-IgM, HEV-IgG, HEV-antigen, and HEV-RNA for HEV species A (HEV-A) and HEV species C (HEV-C)，and further HEV genotyping for those positive for HEV-RNA.</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>HE group</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Clinical residual serum&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Patients from the designated township who met the criteria of &quot;ALT ≥ 2.5 ULN&quot; and born&#xD;
          between 1941 and 1991 will be enrolled in the study.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. From 11&#xD;
               townships（Anfeng、Fuan、Tangyang、Hougang、Liangduo、Qingdong、Shiyan、Shenzao、Wulie、Xuhe、Xin&#xD;
               jie）&#xD;
  &#xD;
            2. ALT ≥ 2.5 ULN&#xD;
  &#xD;
            3. Born between 1941 and 1991&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>32 Years</minimum_age>
      <maximum_age>82 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhang Jun, M.D.</last_name>
      <role>Study Director</role>
      <affiliation>National Institute of Diagnostics and Vaccine Development in infectious disease, Xiamen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhang Jun, PhD</last_name>
      <phone>0592-2184110</phone>
      <email>zhangj@xmu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Dongtai Center for Disease Control and Prevention</name>
        <address>
          <city>Dongtai</city>
          <state>Jiangsu</state>
          <zip>224200</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yang Changlin</last_name>
        <phone>0515-85212669</phone>
        <email>759106863@qq.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.</citation>
      <PMID>20728932</PMID>
    </reference>
    <reference>
      <citation>Zhang J, Zhang XF, Huang SJ, Wu T, Hu YM, Wang ZZ, Wang H, Jiang HM, Wang YJ, Yan Q, Guo M, Liu XH, Li JX, Yang CL, Tang Q, Jiang RJ, Pan HR, Li YM, Shih JW, Ng MH, Zhu FC, Xia NS. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015 Mar 5;372(10):914-22. doi: 10.1056/NEJMoa1406011. Erratum In: N Engl J Med. 2015 Apr 9;372(15):1478.</citation>
      <PMID>25738667</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 19, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 12, 2023</last_update_submitted>
    <last_update_submitted_qc>August 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Xiamen University</investigator_affiliation>
      <investigator_full_name>Jun Zhang</investigator_full_name>
      <investigator_title>professor</investigator_title>
    </responsible_party>
    <keyword>Hepatitis E</keyword>
    <keyword>Test-Negative Design</keyword>
    <keyword>Effectiveness</keyword>
    <keyword>Vaccine</keyword>
    <keyword>Rat hepatitis E virus infection</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hepatitis A</mesh_term>
      <mesh_term>Hepatitis E</mesh_term>
      <mesh_term>Hepatitis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Data sharing requires investigator consent</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05976594
  org study id: PRO-HE-004-2
  nct id: NCT05976594
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This test-negative study is designed to evaluate the long-term effectiveness of hepatitis E
        vaccine (Hecolin®) and to explore the prevalence of rat hepatitis E in Dongtai City.
  In this negative test study, residual clinical serum will be collected from 13 hospitals in
        Dongtai, if it was from patients born between 1941-1991 from 11 towns in Dongtai, who tested
        positive for ALT levels higher than 2.5 times the upper limit of normal (ULN). Detection of
        HEV IgM, IgG, antigen, RNA will be performed to diagnose hepatitis E (HE) in each individual.
        In addition, HE vaccination history will be collect. All the information above will be used
        to evaluate the long-term effectiveness of HE vaccine. Based on the study design, virological
        and serological detection (IgM, IgG, antigen, and RNA) of hepatitis E virus species C (HEV-C)
        will be performed to analyze the prevalence of rat hepatitis E infection in Dongtai.
  observational model: Case-Control
  time perspective: Retrospective
  measure: Rate of hepatitis E infection
  time frame: Two months after sampling
  description: In patients with ALT > 2.5 ULN, HEV infection is diagnosed as positive when two of the following indicators are positive: (1) HEV-IgM; (2) Seroconversion or four-fold increase of HEV-IgG；(3) HEV-RNA; (4) HEV-antigen.
  measure: Rate of rat hepatitis E infection
  time frame: Two months after sampling
  description: In patients with ALT > 2.5 ULN, rat hepatitis E infection is diagnosed as positive when two of the following virologic or serological tests are positive: (1) IgM anti-HEV-C-; (2) IgG anti-HEV-C- seroconversion or four-fold increase；(3) HEV-C-RNA; (4) HEV-C-antigen.
  arm group label: HE group
  description: Subjects who has been diagnosed as HE.
  arm group label: Control group
  description: Subjects who didn't meet the diagnosis criteria of HE.
  intervention type: Diagnostic Test
  intervention name: serology and virology detection of hepatitis E virus
  description: Serum will be tested for HEV serology and virology, including HEV-IgM, HEV-IgG, HEV-antigen, and HEV-RNA for HEV species A (HEV-A) and HEV species C (HEV-C)，and further HEV genotyping for those positive for HEV-RNA.
  arm group label: Control group
  arm group label: HE group
  Clinical residual serum
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 32 Years
  maximum age: 82 Years
  healthy volunteers: No
  last name: Zhang Jun, M.D.
  role: Study Director
  affiliation: National Institute of Diagnostics and Vaccine Development in infectious disease, Xiamen University
  last name: Zhang Jun, PhD
  phone: 0592-2184110
  email: zhangj@xmu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.
  PMID: 20728932
  citation: Zhang J, Zhang XF, Huang SJ, Wu T, Hu YM, Wang ZZ, Wang H, Jiang HM, Wang YJ, Yan Q, Guo M, Liu XH, Li JX, Yang CL, Tang Q, Jiang RJ, Pan HR, Li YM, Shih JW, Ng MH, Zhu FC, Xia NS. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015 Mar 5;372(10):914-22. doi: 10.1056/NEJMoa1406011. Erratum In: N Engl J Med. 2015 Apr 9;372(15):1478.
  PMID: 25738667
  responsible party type: Principal Investigator
  investigator affiliation: Xiamen University
  investigator full name: Jun Zhang
  investigator title: professor
  mesh term: Hepatitis A
  mesh term: Hepatitis E
  mesh term: Hepatitis
  sharing ipd: No
  ipd description: Data sharing requires investigator consent