<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/NCT03811431</url>
  </required_header>
  <id_info>
    <org_study_id>BIOPTICON</org_study_id>
    <nct_id>NCT03811431</nct_id>
  </id_info>
  <brief_title>Contrast Enhanced Ultrasound Guidance Biopsy for the Diagnosis of Liver Tumors</brief_title>
  <acronym>ConCLUDe</acronym>
  <official_title>Real Time Contrast-enhanced Compared to Conventional Ultrasound Guided Biopsy in the Diagnosis of Hepatic Tumors on a Background of Advanced Chronic Liver Disease. A Prospective Clinical Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Iuliu Hatieganu University of Medicine and Pharmacy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Iuliu Hatieganu University of Medicine and Pharmacy</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 main purpose of this study is to compare contrast-enhanced ultrasound guided liver biopsy&#xD;
      (CEUS-LB) with conventional ultrasound guided liver biopsy (US-LB) in the diagnosis of liver&#xD;
      tumors developed on a background of advanced chronic liver diseases. All patients referred to&#xD;
      our department with a CT/MRI diagnosis of hepatic neoplasia will be randomly assigned to&#xD;
      either CEUS-LB or US-LB. All LB will be performed by the same investigator. For the&#xD;
      randomisation the flip coin technique will be used. One investigator without access to&#xD;
      previous C/MRI/US report will do the randomization&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A prospective parallel group clinical trial will be performed. The study protocol was&#xD;
      implemented in our Institute starting January 2011 ending January 1 2020. During this period,&#xD;
      all patients with a suspicion of primary liver neoplasia either on CT or MRI will be&#xD;
      evaluated in different departments from our Institute for possible inclusion. Patients with a&#xD;
      typical aspect of benign FLLs will not be included in the study. Patients fulfilling the&#xD;
      following criteria: presence of cirrhosis or other chronic liver disease (according to a&#xD;
      liver stiffness evaluated by transient elastography higher than 10 kilopascals), Child-Pugh&#xD;
      score no higher than B7 and absence of perihepatic ascites, platelet count &gt; 50.000 per mm3&#xD;
      or an international normalized ratio &lt; 1.6; will be further on sent to the department of&#xD;
      interventional ultrasound. ). All patients referred to interventional department will&#xD;
      underwent a B-mode ultrasound (1 investigator) testing the feasibility of performing liver&#xD;
      biopsy. At this time point the conspicuity of the tumors will be recorded into either poorly&#xD;
      or not poorly visible. Included patients will be randomly divided by another investigator&#xD;
      (T.M.) without access to the previous US, CT or MRI report into two groups: a group that will&#xD;
      underwent US guided liver biopsy (USLB) and another one who will underwent CEUS guided liver&#xD;
      biopsy (CEUSLB). The randomization will be made based of flip coin technique. The side of the&#xD;
      coin (heads-USLB, tails CEUSLB) determined the assignment of each subject. All biopsies will&#xD;
      be performed by the same investigator (Z.S.) with an experience of more than 8 years in&#xD;
      ultrasound interventions. Patients assigned to USLB or CEUSLB will be blinded. The&#xD;
      investigators assessing the outcomes will not be informed about the LB technique used in each&#xD;
      patient. The reasons for performing biopsy will be either inconclusive CT/MRI findings , or&#xD;
      patients with a typical pattern of HCC on CT/MRI in whom a histological diagnosis is&#xD;
      necessary in order to start systemic therapy (sorafenib). Different from other major&#xD;
      society's guidelines, in our country a histological diagnosis of HCC is mandatory in patients&#xD;
      referred for sorafenib treatment. Patients with small FLLs (BCLC 0 or A) and typical aspect&#xD;
      of HCC on CT/MRI will be sent directly to surgery or radiofrequency ablation according to&#xD;
      EASL guidelines.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2011</start_date>
  <completion_date type="Anticipated">January 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2020</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>A prospective parallel group clinical trial</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Investigator</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients in whom contrast enhanced ultrasound guided liver biopsy leads to the final diagnosis as compared to conventional ultrasound guided liver biopsy. The final diagnosis will be assessed based on histological examination.</measure>
    <time_frame>From randomisation until the first documented histological diagnosis. In cases with a negative diagnosis based on histology imaging follow-up using CT or MRI will be carried on for a period of at least 12 months.</time_frame>
    <description>In patients in whom a final histological diagnosis can not be achieved with the use of contrast enhanced or ultrasound guidance a second liver biopsy will be considered if appropriate in the next 3-4 weeks. In cases where a second liver biopsy will be judged not to be necessary a follow-up using imaging techniques will be performed until a final diagnosis is reached.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">138</enrollment>
  <condition>Liver Diseases</condition>
  <arm_group>
    <arm_group_label>CEUS guidance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SonoVue 2, 4 ml</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional US guidance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>No drugs</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Contrast enhanced ultrasound guided liver biopsy</intervention_name>
    <description>Conventional liver biopsy</description>
    <arm_group_label>CEUS guidance</arm_group_label>
    <arm_group_label>Conventional US guidance</arm_group_label>
    <other_name>Ultrasound</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  presence of cirrhosis or other chronic liver disease (according to a liver stiffness&#xD;
             evaluated by transient elastography higher than 10 kilopascals)&#xD;
&#xD;
          -  Child-Pugh score no higher than B7 and absence of perihepatic ascites&#xD;
&#xD;
          -  platelet count &gt; 50.000 per mm3&#xD;
&#xD;
          -  international normalized ratio &lt; 1.6&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  tumors located tin sonography blind areas&#xD;
&#xD;
          -  refuse to sign the informed consent&#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_contact>
    <last_name>Tudor Mocan, MD</last_name>
    <phone>+40 799861946</phone>
    <email>Mocac.Tudor@umfcluj.ro</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zeno Sparchez, MD, PhD</last_name>
    <phone>+40 0729890911</phone>
    <email>zsparchez@yahoo.co.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Regional Institute of Gastroenterology and Hepatology &quot;Octavian Fodor&quot;</name>
      <address>
        <city>Cluj-Napoca</city>
        <state>Please Enter The State Or Province</state>
        <zip>400126</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tudor Mocan</last_name>
      <phone>+40 799 861946</phone>
      <email>Mocan.Tudor@umfcluj.ro</email>
    </contact>
    <contact_backup>
      <last_name>Ioana Rusu</last_name>
      <email>ioana.russu@yahoo.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Romania</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 17, 2019</last_update_submitted>
  <last_update_submitted_qc>January 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Iuliu Hatieganu University of Medicine and Pharmacy</investigator_affiliation>
    <investigator_full_name>Tudor Mocan</investigator_full_name>
    <investigator_title>MD Associate Specialist</investigator_title>
  </responsible_party>
  <keyword>contrast enhanced ultrasound guided liver biopsy</keyword>
  <keyword>ultrasound guided liver biopsy</keyword>
  <keyword>focal liver lesions</keyword>
  <keyword>hepatocellular carcinoma</keyword>
  <keyword>advanced chronic liver disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data for all primary and secondary outcome measures will be made available</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data available within 12 months of study completion</ipd_time_frame>
    <ipd_access_criteria>Data access request will be reviewed by an external Independent review panel.</ipd_access_criteria>
  </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/NCT03811431
org study id: BIOPTICON
nct id: NCT03811431
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main purpose of this study is to compare contrast-enhanced ultrasound guided liver biopsy
      (CEUS-LB) with conventional ultrasound guided liver biopsy (US-LB) in the diagnosis of liver
      tumors developed on a background of advanced chronic liver diseases. All patients referred to
      our department with a CT/MRI diagnosis of hepatic neoplasia will be randomly assigned to
      either CEUS-LB or US-LB. All LB will be performed by the same investigator. For the
      randomisation the flip coin technique will be used. One investigator without access to
      previous C/MRI/US report will do the randomization
A prospective parallel group clinical trial will be performed. The study protocol was
      implemented in our Institute starting January 2011 ending January 1 2020. During this period,
      all patients with a suspicion of primary liver neoplasia either on CT or MRI will be
      evaluated in different departments from our Institute for possible inclusion. Patients with a
      typical aspect of benign FLLs will not be included in the study. Patients fulfilling the
      following criteria: presence of cirrhosis or other chronic liver disease (according to a
      liver stiffness evaluated by transient elastography higher than 10 kilopascals), Child-Pugh
      score no higher than B7 and absence of perihepatic ascites, platelet count > 50.000 per mm3
      or an international normalized ratio < 1.6; will be further on sent to the department of
      interventional ultrasound. ). All patients referred to interventional department will
      underwent a B-mode ultrasound (1 investigator) testing the feasibility of performing liver
      biopsy. At this time point the conspicuity of the tumors will be recorded into either poorly
      or not poorly visible. Included patients will be randomly divided by another investigator
      (T.M.) without access to the previous US, CT or MRI report into two groups: a group that will
      underwent US guided liver biopsy (USLB) and another one who will underwent CEUS guided liver
      biopsy (CEUSLB). The randomization will be made based of flip coin technique. The side of the
      coin (heads-USLB, tails CEUSLB) determined the assignment of each subject. All biopsies will
      be performed by the same investigator (Z.S.) with an experience of more than 8 years in
      ultrasound interventions. Patients assigned to USLB or CEUSLB will be blinded. The
      investigators assessing the outcomes will not be informed about the LB technique used in each
      patient. The reasons for performing biopsy will be either inconclusive CT/MRI findings , or
      patients with a typical pattern of HCC on CT/MRI in whom a histological diagnosis is
      necessary in order to start systemic therapy (sorafenib). Different from other major
      society's guidelines, in our country a histological diagnosis of HCC is mandatory in patients
      referred for sorafenib treatment. Patients with small FLLs (BCLC 0 or A) and typical aspect
      of HCC on CT/MRI will be sent directly to surgery or radiofrequency ablation according to
      EASL guidelines.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A prospective parallel group clinical trial
primary purpose: Diagnostic
masking: Double (Participant, Investigator)
masking description: Investigator
measure: Number of patients in whom contrast enhanced ultrasound guided liver biopsy leads to the final diagnosis as compared to conventional ultrasound guided liver biopsy. The final diagnosis will be assessed based on histological examination.
time frame: From randomisation until the first documented histological diagnosis. In cases with a negative diagnosis based on histology imaging follow-up using CT or MRI will be carried on for a period of at least 12 months.
description: In patients in whom a final histological diagnosis can not be achieved with the use of contrast enhanced or ultrasound guidance a second liver biopsy will be considered if appropriate in the next 3-4 weeks. In cases where a second liver biopsy will be judged not to be necessary a follow-up using imaging techniques will be performed until a final diagnosis is reached.
arm group label: CEUS guidance
arm group type: Experimental
description: SonoVue 2, 4 ml
arm group label: Conventional US guidance
arm group type: Experimental
description: No drugs
intervention type: Procedure
intervention name: Contrast enhanced ultrasound guided liver biopsy
description: Conventional liver biopsy
arm group label: CEUS guidance
arm group label: Conventional US guidance
other name: Ultrasound
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tudor Mocan, MD
phone: +40 799861946
email: Mocac.Tudor@umfcluj.ro
last name: Zeno Sparchez, MD, PhD
phone: +40 0729890911
email: zsparchez@yahoo.co.uk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Romania
responsible party type: Principal Investigator
investigator affiliation: Iuliu Hatieganu University of Medicine and Pharmacy
investigator full name: Tudor Mocan
investigator title: MD Associate Specialist
mesh term: Liver Diseases
sharing ipd: Yes
ipd description: De-identified individual participant data for all primary and secondary outcome measures will be made available
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data available within 12 months of study completion
ipd access criteria: Data access request will be reviewed by an external Independent review panel.