<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/NCT03820271</url>
  </required_header>
  <id_info>
    <org_study_id>K170914J</org_study_id>
    <nct_id>NCT03820271</nct_id>
  </id_info>
  <brief_title>New Prognostic Predictive Models of Mortality of Decompensated Cirrhotic Patients Waiting for Liver Transplantation</brief_title>
  <acronym>SUPERMELD</acronym>
  <official_title>Construction of New Predictive Mathematical Models of Mortality in Decompensated Cirrhotic Patients Who Are Candidates for Liver Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      The MELD score is a predictive model of cirrhosis mortality used in France since 2007 to&#xD;
      prioritize access to liver transplantation for patients enrolled in the national waiting&#xD;
      list. The predictive value of this score was recently revised downward with a C index of the&#xD;
      order of 0.65-0.67 and 20% of the patients enrolled for decompensated cirrhosis have access&#xD;
      to liver transplantation by a subjective system of &quot;expert component&quot; independent of the MELD&#xD;
      because of this lack of precision. The use of the MELD score to individually define access to&#xD;
      the transplant should so be reconsidered. Recently new predictive models of cirrhosis&#xD;
      mortality better than MELD have been developed and new mortality predictors independent of&#xD;
      MELD have been published.&#xD;
&#xD;
      The goal of this study is to design prognostic predictive models of mortality for&#xD;
      decompensated cirrhotic patients enrolled on the national liver transplant waiting list&#xD;
      including known (MELD, MELD Na) as more recent (CLIF-C AD, CLIF - CACLF) predictive models&#xD;
      and new objective predictors studied in combination in order to optimize the system of&#xD;
      allocation of hepatic allografts in France.&#xD;
&#xD;
      The expected benefits of this search are twofold:&#xD;
&#xD;
        -  At the individual level: The possibility for patients at high risk of death but with&#xD;
           intermediate MELD score to be transplanted.&#xD;
&#xD;
        -  Public health plan:&#xD;
&#xD;
             -  Improving the equity of graft allocation system.&#xD;
&#xD;
             -  Decreased mortality in the waiting list by improving the fairness and efficiency of&#xD;
                the graft allocation system, a major public health issue&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2022</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>
    <intervention_model_description>The pre-inclusion visit will be between 1 week and at the latest 2 days before the inclusion visit. The duration of the inclusion period is 24 months. After inclusion, samples at D5, D10 and D14 (additional samples) for sequential analysis of CRP and ammonemia and simple clinical reassessment will be scheduled for the period of hospitalization or routine consultations. Subsequent scheduled visits will take place quarterly until the transplant. Comprehensive nutritional , frailty and CT assessment of sarcopenia (psoas) by abdominal CT without contrast injection will be performed at 6 months as part of the protocol. Additional visits will be scheduled as part of the usual patient follow-up.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>predictive value of the new multivariate prognostic models in patients listed for decompensated cirrhosis</measure>
    <time_frame>Month 3.</time_frame>
    <description>Predictive value of mortality and drop out in the waiting list</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Individual predictive value of each of the new candidate predictors</measure>
    <time_frame>Month 3. Month 6, Month 9, Month 12Month 12</time_frame>
    <description>CRP, copeptin, NT-pro BNP, vitamin D, leucocytes, PMN/lymphocytes ratio, urinary NGal, cystatin C, frailty index, sarcopenia (abdominal tomodensitometry to measure the surface of psoas), caloric intake, encephalopathy (ammonia level, stroop application), and transferrin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications predicted by each of the independent predictors</measure>
    <time_frame>Month 3 Month 6, Month 9, Month 12.Month 12</time_frame>
    <description>infection, renal dysfunction, encephalopathy, bleeding, ACLF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Added predictive value for mortality and drop out of new multivariate prognostic models on MELD (model end stage for liver disease)</measure>
    <time_frame>Months 3, Month 6, Month 9, Month 12.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the predictive value of the CLIF (Chronic LIver Failure)-C (cirhosis) AD (Decompensation) score in decompensated cirrhotics listed without organ failure</measure>
    <time_frame>Months 3, Month 6, Month 9, Month 12.</time_frame>
    <description>death and drop out</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Decompensated Cirrhosis</condition>
  <condition>Liver Transplantation</condition>
  <arm_group>
    <arm_group_label>SuperMELD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SuperMELD</intervention_name>
    <description>The population of this arm will consist of patients newly enrolled in the National Liver Transplantation Waiting List for decompensated cirrhosis, whose liver function and MELD score are assessed at enrollment and then routinely reassessed at least quarterly during the waiting phase.&#xD;
Patients will be followed from their listing to transplantation or discharge or death.</description>
    <arm_group_label>SuperMELD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (≥18 years old) newly registered on national waiting list with main&#xD;
             diagnosis &quot;cirrhosis&quot;&#xD;
&#xD;
          -  Patients enrolled on the national waiting list under the &quot;national liver score&quot;&#xD;
             allocation scheme whether an expert component is considered or not&#xD;
&#xD;
          -  Patients (or trusted person or family member or close relation if the patient is&#xD;
             unable to express consent) who have been informed and signed their informed consent&#xD;
&#xD;
          -  Patients affiliated to a health insurance scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients enrolled with decompensated cirrhosis associated with hepatocellular&#xD;
             carcinoma&#xD;
&#xD;
          -  Patients on AVK (INR and therefore MELD and CLIF scores uninterpretable)&#xD;
&#xD;
          -  Vulnerable population (person under guardianship or curatorship or deprived of liberty&#xD;
             by a judicial decision)&#xD;
&#xD;
          -  Pregnant and / or breastfeeding woman&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Candy Estevez</last_name>
    <role>Study Chair</role>
    <affiliation>APHP DRCI</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Laetitia Gregoire</last_name>
    <role>Study Chair</role>
    <affiliation>APHP URC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christophe Duvoux, PHD</last_name>
    <phone>01 49 81 43 28</phone>
    <phone_ext>+33</phone_ext>
    <email>christophe.duvoux@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Pr Duvoux</name>
      <address>
        <city>Créteil</city>
        <zip>94000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christophe Duvoux, PhD</last_name>
      <phone>0149814328</phone>
      <phone_ext>+33</phone_ext>
      <email>christophe.duvoux@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>May 2, 2022</last_update_submitted>
  <last_update_submitted_qc>May 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver transplantation</keyword>
  <keyword>Predictive prognostic models</keyword>
  <keyword>Decompensated cirrhosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>


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/NCT03820271
org study id: K170914J
nct id: NCT03820271
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The MELD score is a predictive model of cirrhosis mortality used in France since 2007 to
      prioritize access to liver transplantation for patients enrolled in the national waiting
      list. The predictive value of this score was recently revised downward with a C index of the
      order of 0.65-0.67 and 20% of the patients enrolled for decompensated cirrhosis have access
      to liver transplantation by a subjective system of "expert component" independent of the MELD
      because of this lack of precision. The use of the MELD score to individually define access to
      the transplant should so be reconsidered. Recently new predictive models of cirrhosis
      mortality better than MELD have been developed and new mortality predictors independent of
      MELD have been published.

      The goal of this study is to design prognostic predictive models of mortality for
      decompensated cirrhotic patients enrolled on the national liver transplant waiting list
      including known (MELD, MELD Na) as more recent (CLIF-C AD, CLIF - CACLF) predictive models
      and new objective predictors studied in combination in order to optimize the system of
      allocation of hepatic allografts in France.

      The expected benefits of this search are twofold:

        -  At the individual level: The possibility for patients at high risk of death but with
           intermediate MELD score to be transplanted.

        -  Public health plan:

             -  Improving the equity of graft allocation system.

             -  Decreased mortality in the waiting list by improving the fairness and efficiency of
                the graft allocation system, a major public health issue
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The pre-inclusion visit will be between 1 week and at the latest 2 days before the inclusion visit. The duration of the inclusion period is 24 months. After inclusion, samples at D5, D10 and D14 (additional samples) for sequential analysis of CRP and ammonemia and simple clinical reassessment will be scheduled for the period of hospitalization or routine consultations. Subsequent scheduled visits will take place quarterly until the transplant. Comprehensive nutritional , frailty and CT assessment of sarcopenia (psoas) by abdominal CT without contrast injection will be performed at 6 months as part of the protocol. Additional visits will be scheduled as part of the usual patient follow-up.
primary purpose: Other
masking: None (Open Label)
measure: predictive value of the new multivariate prognostic models in patients listed for decompensated cirrhosis
time frame: Month 3.
description: Predictive value of mortality and drop out in the waiting list
measure: Individual predictive value of each of the new candidate predictors
time frame: Month 3. Month 6, Month 9, Month 12Month 12
description: CRP, copeptin, NT-pro BNP, vitamin D, leucocytes, PMN/lymphocytes ratio, urinary NGal, cystatin C, frailty index, sarcopenia (abdominal tomodensitometry to measure the surface of psoas), caloric intake, encephalopathy (ammonia level, stroop application), and transferrin.
measure: Complications predicted by each of the independent predictors
time frame: Month 3 Month 6, Month 9, Month 12.Month 12
description: infection, renal dysfunction, encephalopathy, bleeding, ACLF
measure: Added predictive value for mortality and drop out of new multivariate prognostic models on MELD (model end stage for liver disease)
time frame: Months 3, Month 6, Month 9, Month 12.
measure: Evaluation of the predictive value of the CLIF (Chronic LIver Failure)-C (cirhosis) AD (Decompensation) score in decompensated cirrhotics listed without organ failure
time frame: Months 3, Month 6, Month 9, Month 12.
description: death and drop out
arm group label: SuperMELD
arm group type: Other
intervention type: Other
intervention name: SuperMELD
description: The population of this arm will consist of patients newly enrolled in the National Liver Transplantation Waiting List for decompensated cirrhosis, whose liver function and MELD score are assessed at enrollment and then routinely reassessed at least quarterly during the waiting phase.
Patients will be followed from their listing to transplantation or discharge or death.
arm group label: SuperMELD
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Candy Estevez
role: Study Chair
affiliation: APHP DRCI
last name: Laetitia Gregoire
role: Study Chair
affiliation: APHP URC
last name: Christophe Duvoux, PHD
phone: 01 49 81 43 28
phone ext: +33
email: christophe.duvoux@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Fibrosis
sharing ipd: No