<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/NCT03267290</url>
  </required_header>
  <id_info>
    <org_study_id>201706079MIPA</org_study_id>
    <nct_id>NCT03267290</nct_id>
  </id_info>
  <brief_title>Comparing Diagnostic Accuracy for Liver Tumours Between the Combination of CEUS and CEMRI Versus CECT and CEMRI</brief_title>
  <official_title>A Prospective Clinical Study for Comparing Diagnostic Accuracy for Liver Tumours Between the Combination of Contrast-enhanced Ultrasound and Contrast-enhanced Magnetic Resonance Imaging Versus Contrast-enhanced Computed Tomography and CEMRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
      Hepatocellular carcinoma (HCC) is unique regarding diagnosis because the clinical diagnosis&#xD;
      without pathology proof is accepted. The dynamic image, including contrast-enhanced computed&#xD;
      tomography (CECT) and contrast-enhanced magnetic resonance image (CEMRI) were recognized in&#xD;
      many guidelines for diagnosing the HCC. In contrast to the CT and MRI, ultrasound (US)&#xD;
      with/without contrast is suggested by several societies as the sufficient surveillance&#xD;
      modality. The contrast-enhanced ultrasound (CEUS) has aroused more attentions regarding the&#xD;
      rapid improvement of contrast medium. In this study, the investigators conducted a&#xD;
      prospective, single-center, open-label trial to compare the efficacy and safety of CEUS +&#xD;
      CEMRI in characterizing HCC, in comparison with CECT + CEMRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The liver cancers including hepatocellular carcinoma (HCC) resulted in more than 7,000&#xD;
      mortalities in Taiwan every year. HCC is unique regarding diagnosis because the clinical&#xD;
      diagnosis without pathology proof is accepted. The dynamic image, including contrast-enhanced&#xD;
      computed tomography (CECT) and contrast-enhanced magnetic resonance image (CEMRI) were&#xD;
      recognized in many guidelines for diagnosing the HCC including Taiwan National Health&#xD;
      insurance. Currently established guidelines endorse 3-phasic CT and MRI as first-line&#xD;
      modalities. In contrast to the CT and MRI, ultrasound (US) with/without contrast is suggested&#xD;
      by several societies as the most sufficient surveillance modality. However, the advantage of&#xD;
      US in liver cirrhosis with regenerative nodules is only 32-65% in sensitivity.&#xD;
&#xD;
      The contrast-enhanced ultrasound (CEUS) has aroused more attentions regarding the rapidly&#xD;
      improvement of contrast medium. In addition to Italian association for the study of the&#xD;
      liver, the Japan society has documented CEUS as an integral part in the diagnosis algorism.&#xD;
      Two phases, i.e. vascular phase and Kupffer phase, could be interpreted with second&#xD;
      generation contrast agents, Sonazoid, for differentiating liver tumors. For liver tumor that&#xD;
      failed to present washout phase in CECT or CEMRI, CEUS might be helpful because a tumor lack&#xD;
      of contrast uptake in the Kupffer phase is favouring HCC. However, previous reports were&#xD;
      confined to retrospective studies or small population, and more solid evidence is required to&#xD;
      identify the diagnosis feasibility of CEUS with specific contrast agent.&#xD;
&#xD;
      In this study, the investigators conducted a prospective, single-center, open-label trial to&#xD;
      compare the efficacy and safety of CEUS + CEMRI in characterizing HCC, in comparison with&#xD;
      CECT + CEMRI. 60 patients with liver tumours no larger than 3cm in diameter will be enrolled,&#xD;
      and tumour specimen will be obtained after imaging examination by tumour resection or biopsy.&#xD;
      The primary endpoint is the sensitivity and specificity between the study groups, use the&#xD;
      histology as reference diagnosis. The secondary endpoints include (1) the sensitivity and&#xD;
      specificity of CEUS+CECT, CECT+CEMRI in differential diagnosis of liver tomours as malignant&#xD;
      or benign, use the histology as reference diagnosis, (2) adverse effects, (3) vital signs&#xD;
      (blood pressure, heart rate), and (4) laboratory values (the hematologic, renal and hepatic&#xD;
      function change). Our exploratory endpoint is the detection rate of CEUS+CEMRI, CECT+CEMRI,&#xD;
      use the histology as reference diagnosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">January 11, 2019</completion_date>
  <primary_completion_date type="Actual">November 29, 2018</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The sensitivity and specificity of the blinded read of CEUS+CEMRI and CECT+CEMRI in characterization of HCC</measure>
    <time_frame>up to 1 year</time_frame>
    <description>the 95% two-sided confidence interval will be presented for both sensitivity and specificity in characterization of HCC</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The sensitivity and specificity of the blinded read of CEUS+CEMRI and CECT+CEMRI in differential diagnosis of liver tumours</measure>
    <time_frame>up to 1 year</time_frame>
    <description>the 95% two-sided confidence interval will be presented for both sensitivity and specificity in differential diagnosis of liver tumours</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Hepatocellular Carcinoma (HCC)</condition>
  <arm_group>
    <arm_group_label>Sonazoid- CEUS+CEMRI or CECT+CEMRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Comparing Diagnostic Accuracy for Liver Tumours Between the Combination of CEUS and CEMRI Versus CECT and CEMRI</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Sonazoid- CEUS, CEMRI, CECT</intervention_name>
    <description>Sonazoid- CEUS+CEMRI in a characterization of HCC, in comparison with CECT+CEMRI.</description>
    <arm_group_label>Sonazoid- CEUS+CEMRI or CECT+CEMRI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 20-70&#xD;
&#xD;
          2. All patients presented with newly diagnosed liver lesion(s) with initial impression of&#xD;
             malignancy.&#xD;
&#xD;
          3. Lesions no larger than 3cm in diameter.&#xD;
&#xD;
          4. Signed and dated informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The lesion with previously documented histology&#xD;
&#xD;
          2. The lesion previously treated with Percutaneous Ethanol Injection, Radiofrequency&#xD;
             Ablation, or Transarterial Chemoembolization&#xD;
&#xD;
          3. The lesion will not have histological confirmation after differential diagnosis&#xD;
&#xD;
          4. The subject had known hypersensitivity to any component of Sonazoid, including a&#xD;
             history of allergies to eggs or egg products (i.e., manifested by full body rash,&#xD;
             respiratory difficulty, oral or laryngeal swelling, hypotension or shock).&#xD;
&#xD;
          5. The subject was considered to be unsuitable to participate in the study by the&#xD;
             investigator.&#xD;
&#xD;
          6. The subject was known to have a right-to-left shunt, severe pulmonary hypertension&#xD;
             (pulmonary artery pressure &gt;90 mmHg) or uncontrolled systemic hypertension.&#xD;
&#xD;
          7. The subject had a recent acute coronary syndrome or clinically unstable ischaemic&#xD;
             cardiac disease, including: evolving or ongoing myocardial infarction, typical angina&#xD;
             at rest within the last 7 days, significant worsening of cardiac symptoms within the&#xD;
             last 7 days, recent coronary artery intervention or other factors suggesting clinical&#xD;
             instability (e.g., recent deterioration of electrocardiogram, laboratory or clinical&#xD;
             findings), acute cardiac failure, Class III/IV cardiac failure, or severe rhythm&#xD;
             disorders.&#xD;
&#xD;
          8. The subject had adult respiratory distress syndrome, severe emphysema, pulmonary&#xD;
             vasculitis, or a history of pulmonary emboli.&#xD;
&#xD;
          9. The subject had known thrombosis within the liver, or portal, or mesenteric veins.&#xD;
&#xD;
         10. The patient with iodine/Gd allergy, lower epidermal growth factor receptor level(&lt;50),&#xD;
             liver/renal dysfunction, and other condition that unsuitable to receive contrast&#xD;
&#xD;
         11. Pregnant and breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kai-Wen Huang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>August 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>June 29, 2020</last_update_submitted>
  <last_update_submitted_qc>June 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 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>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Liver Neoplasms</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/NCT03267290
org study id: 201706079MIPA
nct id: NCT03267290
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Hepatocellular carcinoma (HCC) is unique regarding diagnosis because the clinical diagnosis
      without pathology proof is accepted. The dynamic image, including contrast-enhanced computed
      tomography (CECT) and contrast-enhanced magnetic resonance image (CEMRI) were recognized in
      many guidelines for diagnosing the HCC. In contrast to the CT and MRI, ultrasound (US)
      with/without contrast is suggested by several societies as the sufficient surveillance
      modality. The contrast-enhanced ultrasound (CEUS) has aroused more attentions regarding the
      rapid improvement of contrast medium. In this study, the investigators conducted a
      prospective, single-center, open-label trial to compare the efficacy and safety of CEUS +
      CEMRI in characterizing HCC, in comparison with CECT + CEMRI.
The liver cancers including hepatocellular carcinoma (HCC) resulted in more than 7,000
      mortalities in Taiwan every year. HCC is unique regarding diagnosis because the clinical
      diagnosis without pathology proof is accepted. The dynamic image, including contrast-enhanced
      computed tomography (CECT) and contrast-enhanced magnetic resonance image (CEMRI) were
      recognized in many guidelines for diagnosing the HCC including Taiwan National Health
      insurance. Currently established guidelines endorse 3-phasic CT and MRI as first-line
      modalities. In contrast to the CT and MRI, ultrasound (US) with/without contrast is suggested
      by several societies as the most sufficient surveillance modality. However, the advantage of
      US in liver cirrhosis with regenerative nodules is only 32-65% in sensitivity.

      The contrast-enhanced ultrasound (CEUS) has aroused more attentions regarding the rapidly
      improvement of contrast medium. In addition to Italian association for the study of the
      liver, the Japan society has documented CEUS as an integral part in the diagnosis algorism.
      Two phases, i.e. vascular phase and Kupffer phase, could be interpreted with second
      generation contrast agents, Sonazoid, for differentiating liver tumors. For liver tumor that
      failed to present washout phase in CECT or CEMRI, CEUS might be helpful because a tumor lack
      of contrast uptake in the Kupffer phase is favouring HCC. However, previous reports were
      confined to retrospective studies or small population, and more solid evidence is required to
      identify the diagnosis feasibility of CEUS with specific contrast agent.

      In this study, the investigators conducted a prospective, single-center, open-label trial to
      compare the efficacy and safety of CEUS + CEMRI in characterizing HCC, in comparison with
      CECT + CEMRI. 60 patients with liver tumours no larger than 3cm in diameter will be enrolled,
      and tumour specimen will be obtained after imaging examination by tumour resection or biopsy.
      The primary endpoint is the sensitivity and specificity between the study groups, use the
      histology as reference diagnosis. The secondary endpoints include (1) the sensitivity and
      specificity of CEUS+CECT, CECT+CEMRI in differential diagnosis of liver tomours as malignant
      or benign, use the histology as reference diagnosis, (2) adverse effects, (3) vital signs
      (blood pressure, heart rate), and (4) laboratory values (the hematologic, renal and hepatic
      function change). Our exploratory endpoint is the detection rate of CEUS+CEMRI, CECT+CEMRI,
      use the histology as reference diagnosis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: The sensitivity and specificity of the blinded read of CEUS+CEMRI and CECT+CEMRI in characterization of HCC
time frame: up to 1 year
description: the 95% two-sided confidence interval will be presented for both sensitivity and specificity in characterization of HCC
measure: The sensitivity and specificity of the blinded read of CEUS+CEMRI and CECT+CEMRI in differential diagnosis of liver tumours
time frame: up to 1 year
description: the 95% two-sided confidence interval will be presented for both sensitivity and specificity in differential diagnosis of liver tumours
arm group label: Sonazoid- CEUS+CEMRI or CECT+CEMRI
arm group type: Experimental
description: Comparing Diagnostic Accuracy for Liver Tumours Between the Combination of CEUS and CEMRI Versus CECT and CEMRI
intervention type: Diagnostic Test
intervention name: Sonazoid- CEUS, CEMRI, CECT
description: Sonazoid- CEUS+CEMRI in a characterization of HCC, in comparison with CECT+CEMRI.
arm group label: Sonazoid- CEUS+CEMRI or CECT+CEMRI
criteria: 
gender: All
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: No
last name: Kai-Wen Huang, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Neoplasms
sharing ipd: No