<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/NCT03834285</url>
  </required_header>
  <id_info>
    <org_study_id>238575</org_study_id>
    <nct_id>NCT03834285</nct_id>
  </id_info>
  <brief_title>Liver Disease in Pregnancy</brief_title>
  <official_title>EASL: European Registry of Liver Disease in Pregnancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Association for the Study of the Liver</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College Hospital NHS 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>
      Liver Diseases in pregnancy represents rare disorders and current data is derived primarily&#xD;
      from single centres and retrospective cohorts. Moreover, the population prevalence of these&#xD;
      diseases is low and to-date, it has proven difficult to generate reliable data at a patient&#xD;
      level.&#xD;
&#xD;
      This is a multi-center, prospective cohort study that will open at 3 centers within the UK;&#xD;
      and 4 centers in the European Union. The investigators will aim to collect data and blood&#xD;
      samples at various time points, for patients presenting with liver disease during pregnancy.&#xD;
      The main rationale behind this study is to establish a platform that enables detailed review&#xD;
      of the outcomes of these rare diseases; to help classify and stratify patients according to&#xD;
      risk and develop interventional studies and care pathways to improve overall outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objectives of the study are as follows:&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      To determine the characteristic physiological and biological changes exhibited by females who&#xD;
      develop the following liver diseases during pregnancy.&#xD;
&#xD;
        -  Acute fatty liver of pregnancy&#xD;
&#xD;
        -  Severe cholestasis of pregnancy&#xD;
&#xD;
        -  Severe HELLP syndrome/hypertensive disease&#xD;
&#xD;
        -  Pre-existing cirrhosis and pregnancy This will be determined through analysis of the&#xD;
           standard of care imaging (Liver Ultrasound and Transient Elastography) and blood results&#xD;
           (liver function tests, white blood cells, platelets and scoring systems for assessing&#xD;
           the severity of liver disease (ALBI, APRI, FIB4 and ELF scores). These results will be&#xD;
           analysed over the course of the participant's pregnancy and again at delivery, to&#xD;
           explore any particularly distinguishing parameter changes for each disease group.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        1. To determine the change in the reported quality of life of these participants either&#xD;
           from diagnosis of pregnancy-associated liver disease or confirmation of pregnancy for&#xD;
           pre-existing cirrhotic patients - up to 3 months' post-delivery.&#xD;
&#xD;
        2. To determine the mitochondrial DNA content of blood from patients with Acute Fatty Liver&#xD;
           of Pregnancy.&#xD;
&#xD;
        3. Create an associated pan-European bio-resource (whole blood and serum) collection, which&#xD;
           will offer an opportunity for ongoing collaborative translational research. Each&#xD;
           participant will be given the option of donating additional research samples (15ml) of&#xD;
           blood at each visit under the study for the bio-resource.&#xD;
&#xD;
      Data from cirrhotic patients will be collected from pre-pregnancy and during the first,&#xD;
      second and third trimesters as well as at delivery and post-partum. Data from patients with&#xD;
      AFLP/HELLP/ICP will be collected from pre-diagnosis, at first presentation of liver disease,&#xD;
      at peak of liver disease, during the recovery period from peak liver disease as well as at&#xD;
      delivery and post-partum.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 9, 2019</start_date>
  <completion_date type="Anticipated">April 8, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 8, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Overall maternal and fetal health during pregnancy and post-delivery in females with liver disease</measure>
    <time_frame>Data to be collected from pre-pregnancy to 3 months post-delivery</time_frame>
    <description>Data from 100 patients will be collected across the EU who have either pre-exisiting cirrhosis or one of the three pregnancy-associated liver diseases that are to be studied in this protocol (AFLP, HELLP, ICP)</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Pregnancy Disease</condition>
  <condition>Cirrhosis, Liver</condition>
  <condition>HELLP Syndrome</condition>
  <condition>AFLP - Acute Fatty Liver of Pregnancy</condition>
  <condition>Intrahepatic Cholestasis of Pregnancy</condition>
  <arm_group>
    <arm_group_label>Cirrhosis in pregnancy</arm_group_label>
    <description>Cirrhotic patients with a confirmed pregnancy will be placed into Cohort 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pregnancy-associated liver diseases</arm_group_label>
    <description>Patients who develop Acute Fatty Liver of Pregnancy, HELLP Syndrome / Intrahepatic Cholestasis of pregnancy will be placed into Cohort 2.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Liver Diseases in pregnancy represent rare disorders and the numbers of patients affected&#xD;
        in the overall population is low and therefore, it has proven difficult to generate&#xD;
        reliable data. For example, the numbers of patients affected with these conditions in&#xD;
        Europe are as follows:&#xD;
&#xD;
          -  Acute Fatty Liver affects 1:20,000 pregnant women&#xD;
&#xD;
          -  Severe Cholestasis - 1:3,000 pregnant women&#xD;
&#xD;
          -  Severe haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) requiring&#xD;
             transfer to a liver transplant centre or specialised hepatopancreatobiliary(HPB)&#xD;
             centre at best estimate represents less than 0.01% of pregnancies.&#xD;
&#xD;
        Patients with pre-existing cirrhosis and pregnancy represent approximately 0.003% of&#xD;
        pregnancies, yet, to-date, less than 5 reliable publications exist in the literature to&#xD;
        inform patient management.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female patients older than 18 years of age, willing and able to sign written informed&#xD;
             consent.&#xD;
&#xD;
          2. Pregnant and presenting with any one of the following conditions (confirmed by local&#xD;
             diagnosis):&#xD;
&#xD;
               -  Acute fatty liver of pregnancy&#xD;
&#xD;
               -  Severe cholestasis of pregnancy&#xD;
&#xD;
               -  Severe HELLP syndrome /hypertensive disease&#xD;
&#xD;
               -  Pre-existing cirrhosis and pregnancy&#xD;
&#xD;
          3. Able to provide written informed consent&#xD;
&#xD;
          4. Willing to provide access to records to necessary data can be collected.&#xD;
&#xD;
          5. Willing to complete additional quality of life questionnaires as per protocol.&#xD;
&#xD;
          6. Willing to consider donation of optional blood samples as per protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Unable to provide written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnancy study, so all participants must be female.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Heneghan</last_name>
    <role>Study Chair</role>
    <affiliation>King's College Hospital NHS Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joe Montebello</last_name>
    <phone>0203 299 5303</phone>
    <phone_ext>5303</phone_ext>
    <email>j.montebello@nhs.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>King's College Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Heneghan</last_name>
      <email>michael.heneghan@nhs.net</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>March 25, 2020</last_update_submitted>
  <last_update_submitted_qc>March 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Cholestasis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Cholestasis, Intrahepatic</mesh_term>
    <mesh_term>HELLP Syndrome</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/NCT03834285
org study id: 238575
nct id: NCT03834285
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Liver Diseases in pregnancy represents rare disorders and current data is derived primarily
      from single centres and retrospective cohorts. Moreover, the population prevalence of these
      diseases is low and to-date, it has proven difficult to generate reliable data at a patient
      level.

      This is a multi-center, prospective cohort study that will open at 3 centers within the UK;
      and 4 centers in the European Union. The investigators will aim to collect data and blood
      samples at various time points, for patients presenting with liver disease during pregnancy.
      The main rationale behind this study is to establish a platform that enables detailed review
      of the outcomes of these rare diseases; to help classify and stratify patients according to
      risk and develop interventional studies and care pathways to improve overall outcome.
The objectives of the study are as follows:

      Primary Objective:

      To determine the characteristic physiological and biological changes exhibited by females who
      develop the following liver diseases during pregnancy.

        -  Acute fatty liver of pregnancy

        -  Severe cholestasis of pregnancy

        -  Severe HELLP syndrome/hypertensive disease

        -  Pre-existing cirrhosis and pregnancy This will be determined through analysis of the
           standard of care imaging (Liver Ultrasound and Transient Elastography) and blood results
           (liver function tests, white blood cells, platelets and scoring systems for assessing
           the severity of liver disease (ALBI, APRI, FIB4 and ELF scores). These results will be
           analysed over the course of the participant's pregnancy and again at delivery, to
           explore any particularly distinguishing parameter changes for each disease group.

      Secondary Objectives

        1. To determine the change in the reported quality of life of these participants either
           from diagnosis of pregnancy-associated liver disease or confirmation of pregnancy for
           pre-existing cirrhotic patients - up to 3 months' post-delivery.

        2. To determine the mitochondrial DNA content of blood from patients with Acute Fatty Liver
           of Pregnancy.

        3. Create an associated pan-European bio-resource (whole blood and serum) collection, which
           will offer an opportunity for ongoing collaborative translational research. Each
           participant will be given the option of donating additional research samples (15ml) of
           blood at each visit under the study for the bio-resource.

      Data from cirrhotic patients will be collected from pre-pregnancy and during the first,
      second and third trimesters as well as at delivery and post-partum. Data from patients with
      AFLP/HELLP/ICP will be collected from pre-diagnosis, at first presentation of liver disease,
      at peak of liver disease, during the recovery period from peak liver disease as well as at
      delivery and post-partum.
observational model: Cohort
time perspective: Prospective
measure: Overall maternal and fetal health during pregnancy and post-delivery in females with liver disease
time frame: Data to be collected from pre-pregnancy to 3 months post-delivery
description: Data from 100 patients will be collected across the EU who have either pre-exisiting cirrhosis or one of the three pregnancy-associated liver diseases that are to be studied in this protocol (AFLP, HELLP, ICP)
arm group label: Cirrhosis in pregnancy
description: Cirrhotic patients with a confirmed pregnancy will be placed into Cohort 1.
arm group label: Pregnancy-associated liver diseases
description: Patients who develop Acute Fatty Liver of Pregnancy, HELLP Syndrome / Intrahepatic Cholestasis of pregnancy will be placed into Cohort 2.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Pregnancy study, so all participants must be female.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Heneghan
role: Study Chair
affiliation: King's College Hospital NHS Trust
last name: Joe Montebello
phone: 0203 299 5303
phone ext: 5303
email: j.montebello@nhs.net
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Cholestasis
mesh term: Liver Cirrhosis
mesh term: Cholestasis, Intrahepatic
mesh term: HELLP Syndrome
sharing ipd: No