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/NCT05971108</url>
    </required_header>
    <id_info>
      <org_study_id>B01938</org_study_id>
      <nct_id>NCT05971108</nct_id>
    </id_info>
    <brief_title>Real-world Elecsys® GAAD Implementation and Validation to Improve Surveillance and Early Detection of HCC</brief_title>
    <acronym>REVISE-HCC</acronym>
    <official_title>Real-world Elecsys® GAAD Algorithm Implementation and Validation to Improve Surveillance and Early Detection of Hepatocellular Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Manchester University NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Manchester</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Roche Pharma AG</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Unity Insights</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Imperial College London</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Manchester University NHS Foundation Trust</source>
    <oversight_info>
      <has_dmc>Yes</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>
        Patients with liver cirrhosis are at high risk of developing hepatocellular carcinoma (HCC)&#xD;
        which implies significant mortality. At present current surveillance methods detect&#xD;
        hepatocellular carcinomas at a late stage resulting in few treatment options for patients&#xD;
        and, in the majority of cases, premature death.&#xD;
  &#xD;
        The goal of this study is to implement Elecsys® GAAD in real-world hepatocellular carcinoma&#xD;
        surveillance for those with liver cirrhosis.&#xD;
  &#xD;
        The main questions it aims to answer are:&#xD;
  &#xD;
          -  Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway&#xD;
             increase early detection of HCC?&#xD;
  &#xD;
          -  Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway reduce&#xD;
             false positive tests and unnecessary confirmatory investigations?&#xD;
  &#xD;
          -  Does the new surveillance pathway improve adherence?&#xD;
  &#xD;
        Researchers will compare Elecsys® GAAD with standard of care tests to see if it results in&#xD;
        earlier detection of hepatocellular carcinoma and will explore potential improvements to the&#xD;
        surveillance pathway.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2030</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2030</primary_completion_date>
    <phase>N/A</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>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of hepatocellular carcinoma diagnosis</measure>
      <time_frame>2 years</time_frame>
      <description>Incidence recorded as number of cases per study cohort</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stage of hepatocellular carcinoma at diagnosis</measure>
      <time_frame>2 years</time_frame>
      <description>Barcelona Clinic Liver Cancer (BCLC) stage 0-D</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Rates of false positives for each combination of diagnostic tests</measure>
      <time_frame>2 years</time_frame>
      <description>Count (%) of True/False positives for each test (against magnetic resonance imaging (MRI) / computerised tomography (CT)) will be reported.&#xD;
  Results from different tests (and their (meaningful) combination) will be tabulated against each other:&#xD;
  Alpha-fetoprotein (AFP) vs GAAD&#xD;
  Ultrasound scan (USS) vs GAAD&#xD;
  AFP+ USS vs GAAD&#xD;
  AFP+USS vs GAAD +USS&#xD;
  AFP/GAAD/USS/AFP+USS/GAAD+USS vs MRI/CT for those who proceed to confirmatory imaging.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of curative treatment</measure>
      <time_frame>2 years</time_frame>
      <description>Rates of curative treatment being offered (%) will be recorded on an intention to treat (ITT) basis from Multi-Disciplinary Team (MDT) meeting outcomes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of adherence</measure>
      <time_frame>2 years</time_frame>
      <description>• Attendance rates for biannual surveillance appointments (%), within predefined tolerance of 5-9 months post previous appointment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of discontinuation</measure>
      <time_frame>2 years</time_frame>
      <description>• Count (%) of surveillance discontinuation, defined as no visit &gt;12 months.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Survival rates</measure>
      <time_frame>7 years</time_frame>
      <description>Long-term follow up data will be collected to determine rates of survival following HCC diagnosis at 1-year, 3-years and 5-years.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">600</enrollment>
    <condition>Liver Cirrhosis</condition>
    <condition>Hepatocellular Carcinoma</condition>
    <arm_group>
      <arm_group_label>Patients with liver cirrhosis eligible for HCC Surveillance</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Real-world HCC surveillance cohort will be exposed to Elecsys® GAAD in parallel with standard of care tests.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Elecsys® GAAD</intervention_name>
      <description>Elecsys® GAAD is a CE marked in vitro diagnostic (IVD) multivariate index assay, intended as an aid in the diagnosis of early-stage HCC. It provides a semi quantitative result by combining in an algorithm the quantitative measurements of Elecsys® AFP (alpha-fetoprotein) and Elecsys® PIVKA-II (protein induced by vitamin K absence II) levels in serum and plasma, with gender and age. Clinical evidence showed that Elecsys® GAAD had high performance in detecting HCC (sensitivity 86.5%), particularly early stage (sensitivity 78.9%), with 91.4% specificity for both early and all stages, out-performing current standard of care (Chan et al. 2021). Elecsys® GAAD may be integrated into current surveillance practice to increase early-stage HCC detection rate, reduce unnecessary onward investigations and patient anxiety.</description>
      <arm_group_label>Patients with liver cirrhosis eligible for HCC Surveillance</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          • Patients with known liver cirrhosis referred into or already under hepatocellular&#xD;
          carcinoma surveillance&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnancy/breast-feeding.&#xD;
  &#xD;
            -  Patients who do not have liver cirrhosis&#xD;
  &#xD;
            -  Patients who already have hepatocellular carcinoma&#xD;
  &#xD;
            -  Any patient who is unable to understand, retain and weigh information to make an&#xD;
               informed decision, will be excluded from the study. The investigators will use every&#xD;
               opportunity, including tele-interpretation services to minimise this from happening.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Biological sex used in diagnostic algorithm</gender_description>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Varinder Athwal, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Manchester University NHS Foundation Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Varinder Athwal, PhD</last_name>
      <phone>0300 3309444</phone>
      <email>varinder.athwal@mft.nhs.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Christopher Mysko, MBBS MClinEd</last_name>
      <phone>0300 3309444</phone>
      <email>christopher.mysko@postgrad.manchester.ac.uk</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>GAAD</keyword>
    <keyword>hepatocellular carcinoma</keyword>
    <keyword>cirrhosis</keyword>
    <keyword>health inequalities</keyword>
    <keyword>surveillance</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
      <mesh_term>Liver Cirrhosis</mesh_term>
      <mesh_term>Fibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05971108
  org study id: B01938
  nct id: NCT05971108
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Patients with liver cirrhosis are at high risk of developing hepatocellular carcinoma (HCC)
        which implies significant mortality. At present current surveillance methods detect
        hepatocellular carcinomas at a late stage resulting in few treatment options for patients
        and, in the majority of cases, premature death.
  
        The goal of this study is to implement Elecsys® GAAD in real-world hepatocellular carcinoma
        surveillance for those with liver cirrhosis.
  
        The main questions it aims to answer are:
  
          -  Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway
             increase early detection of HCC?
  
          -  Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway reduce
             false positive tests and unnecessary confirmatory investigations?
  
          -  Does the new surveillance pathway improve adherence?
  
        Researchers will compare Elecsys® GAAD with standard of care tests to see if it results in
        earlier detection of hepatocellular carcinoma and will explore potential improvements to the
        surveillance pathway.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Incidence of hepatocellular carcinoma diagnosis
  time frame: 2 years
  description: Incidence recorded as number of cases per study cohort
  measure: Stage of hepatocellular carcinoma at diagnosis
  time frame: 2 years
  description: Barcelona Clinic Liver Cancer (BCLC) stage 0-D
  measure: Rates of false positives for each combination of diagnostic tests
  time frame: 2 years
  description: Count (%) of True/False positives for each test (against magnetic resonance imaging (MRI) / computerised tomography (CT)) will be reported.
  Results from different tests (and their (meaningful) combination) will be tabulated against each other:
  Alpha-fetoprotein (AFP) vs GAAD
  Ultrasound scan (USS) vs GAAD
  AFP+ USS vs GAAD
  AFP+USS vs GAAD +USS
  AFP/GAAD/USS/AFP+USS/GAAD+USS vs MRI/CT for those who proceed to confirmatory imaging.
  measure: Rates of curative treatment
  time frame: 2 years
  description: Rates of curative treatment being offered (%) will be recorded on an intention to treat (ITT) basis from Multi-Disciplinary Team (MDT) meeting outcomes.
  measure: Rates of adherence
  time frame: 2 years
  description: • Attendance rates for biannual surveillance appointments (%), within predefined tolerance of 5-9 months post previous appointment.
  measure: Rates of discontinuation
  time frame: 2 years
  description: • Count (%) of surveillance discontinuation, defined as no visit >12 months.
  measure: Survival rates
  time frame: 7 years
  description: Long-term follow up data will be collected to determine rates of survival following HCC diagnosis at 1-year, 3-years and 5-years.
  arm group label: Patients with liver cirrhosis eligible for HCC Surveillance
  arm group type: Experimental
  description: Real-world HCC surveillance cohort will be exposed to Elecsys® GAAD in parallel with standard of care tests.
  intervention type: Diagnostic Test
  intervention name: Elecsys® GAAD
  description: Elecsys® GAAD is a CE marked in vitro diagnostic (IVD) multivariate index assay, intended as an aid in the diagnosis of early-stage HCC. It provides a semi quantitative result by combining in an algorithm the quantitative measurements of Elecsys® AFP (alpha-fetoprotein) and Elecsys® PIVKA-II (protein induced by vitamin K absence II) levels in serum and plasma, with gender and age. Clinical evidence showed that Elecsys® GAAD had high performance in detecting HCC (sensitivity 86.5%), particularly early stage (sensitivity 78.9%), with 91.4% specificity for both early and all stages, out-performing current standard of care (Chan et al. 2021). Elecsys® GAAD may be integrated into current surveillance practice to increase early-stage HCC detection rate, reduce unnecessary onward investigations and patient anxiety.
  arm group label: Patients with liver cirrhosis eligible for HCC Surveillance
  criteria: 
  gender: All
  gender based: Yes
  gender description: Biological sex used in diagnostic algorithm
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Varinder Athwal, PhD
  role: Principal Investigator
  affiliation: Manchester University NHS Foundation Trust
  last name: Varinder Athwal, PhD
  phone: 0300 3309444
  email: varinder.athwal@mft.nhs.uk
  last name: Christopher Mysko, MBBS MClinEd
  phone: 0300 3309444
  email: christopher.mysko@postgrad.manchester.ac.uk
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular
  mesh term: Liver Cirrhosis
  mesh term: Fibrosis
  sharing ipd: No