<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/NCT03040323</url>
  </required_header>
  <id_info>
    <org_study_id>1609504711</org_study_id>
    <nct_id>NCT03040323</nct_id>
  </id_info>
  <brief_title>Prospective Analysis of Value of Contrast-enhanced Sonography During Biopsies of Focal Liver Masses</brief_title>
  <official_title>Prospective Analysis of Value of Contrast-enhanced Sonography During Biopsies of Focal Liver Masses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators plan to compare complication and success rates between two methods of&#xD;
      ultrasound guidance for biopsy of liver lesions, contrast-enhanced and the current protocol&#xD;
      without contrast.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As a major oncology and hepatology center, the investigators perform about 3-5 guided&#xD;
      biopsies for liver tumors weekly. Ultrasound is the preferred modality for imaging biopsies&#xD;
      due to its ability to visualize and position the biopsy needle in real time with high&#xD;
      accuracy and safety, is nonionizing, and is quicker compared to other techniques, especially&#xD;
      CT-guided biopsies. The failure rate of ultrasound guided liver biopsies (including cases&#xD;
      where biopsy was declined to be performed due to lack of lesion visibility) is about 10%. By&#xD;
      comparison, in the investigators' practice genotyping of metastatic tumors, with multiple&#xD;
      core biopsies, is often requested for entry into oncology trials, and failure of tumor&#xD;
      genotyping after biopsy is estimated to be about 30%.&#xD;
&#xD;
      Recently, the first ultrasound contrast agent was FDA-approved for characterization of liver&#xD;
      lesions [sulfur hexafluoride lipid-type A microspheres (Lumason, Bracco Diagnostics, Monroe&#xD;
      Township, NJ)]. The microbubble agent is deemed safe, including in cardiac failure patients&#xD;
      and those with chronic airway obstruction. Injecting microbubbles may allow better&#xD;
      visualization of lesions and adjacent vasculature by enhancing the microvasculature and&#xD;
      adjacent vessels and potentially reduce incidence of failed biopsy or bleeding complications.&#xD;
      In addition, determination of necrotic regions in a lesion may allow better direction of&#xD;
      biopsy.&#xD;
&#xD;
      Yet there is limited literature on the use of ultrasound contrast agents for improving&#xD;
      targeted liver biopsies. The investigators intend to prospectively assess the non-diagnostic&#xD;
      biopsy and complication rates in a group of patients who undergo contrast-enhanced&#xD;
      ultrasonography (CEUS) using microbubbles at the time of biopsy. The investigators will then&#xD;
      compare the results from this group with the failure and complication rate from a control&#xD;
      group of patients undergoing the standard US-guided biopsy procedure. Over 12 months the&#xD;
      investigators expect to perform approximately 200 biopsies. Power analysis suggests that 125&#xD;
      patients in both contrast-enhanced sonography and control groups, each, are required. The&#xD;
      investigators should be able to enroll sufficient patients in 18 months&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient patient recruitment. Data lost following departure of key personnel&#xD;
  </why_stopped>
  <start_date type="Actual">December 22, 2016</start_date>
  <completion_date type="Actual">July 6, 2018</completion_date>
  <primary_completion_date type="Actual">June 30, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Two interventional arms, selected by day of month; 1) biopsy with Lumason, 2) biopsy with placebos</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Patients will not be informed of diagnostic arm.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Complication Rate</measure>
    <time_frame>30 days</time_frame>
    <description>Complication will be defined as 1) bleeding seen on post-biopsy CT or US, 2) drop in hemoglobin of more than 1.5 g/dL within one week after biopsy, or 3) need for hepatic artery embolization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Success Rate</measure>
    <time_frame>30 days</time_frame>
    <description>Biopsy sample being sufficient for histological diagnosis and/or complete genotyping.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">83</enrollment>
  <condition>Liver Biopsy</condition>
  <arm_group>
    <arm_group_label>biopsy with Lumason</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>liver biopsy performed with prior contrast enhancement with Lumason 60.7Mg Powder for Injection (experimental method)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>biopsy with placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>liver biopsy performed without prior contrast enhancement (standard method)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lumason 60.7Mg Powder for Injection</intervention_name>
    <description>Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy</description>
    <arm_group_label>biopsy with Lumason</arm_group_label>
    <other_name>Lumason</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebos injected prior to ultrasound-guided biopsy</description>
    <arm_group_label>biopsy with placebos</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females&#xD;
&#xD;
          2. Age 18 years or greater&#xD;
&#xD;
          3. Scheduled to undergo liver biopsy with ultrasound guidance at a performance site&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Liver biopsy is not intended to obtain tissue from a specific lesion&#xD;
&#xD;
          2. Known or suspected cardiac shunt&#xD;
&#xD;
          3. History of hypersensitivity to any active or inactive ingredients in Lumason&#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>Kumar Sandrasegaran, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Indiana University Health</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <results_first_submitted>June 25, 2019</results_first_submitted>
  <results_first_submitted_qc>July 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 24, 2019</results_first_posted>
  <last_update_submitted>July 24, 2019</last_update_submitted>
  <last_update_submitted_qc>July 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Jordan K. Swensson</investigator_full_name>
    <investigator_title>Assistant Professor Clinical Radiology</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 24, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03040323/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. The PI has left the institution and no information is available regarding how many participants Started and Completed the study in each arm</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Biopsy With Lumason</title>
          <description>Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy</description>
        </group>
        <group group_id="P2">
          <title>Biopsy With Placebos</title>
          <description>Placebos injected prior to ultrasound-guided biopsy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0">No information available regarding how many participants Started and Completed the study in each arm</participants>
                <participants group_id="P2" count="0">No information available regarding how many participants Started and Completed the study in each arm</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. The PI has left the institution and it is not clear if Baseline data were collected. No Baseline data are available</population>
      <group_list>
        <group group_id="B1">
          <title>Biopsy With Lumason</title>
          <description>Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy</description>
        </group>
        <group group_id="B2">
          <title>Biopsy With Placebos</title>
          <description>Placebos injected prior to ultrasound-guided biopsy.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="0"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                </category>
                <category>
                  <title>Male</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <class_list>
            <class>
              <title>United States</title>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Insufficient patient recruitment and data was lost following departure of key study personnel</title>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Complication Rate</title>
        <description>Complication will be defined as 1) bleeding seen on post-biopsy CT or US, 2) drop in hemoglobin of more than 1.5 g/dL within one week after biopsy, or 3) need for hepatic artery embolization.</description>
        <time_frame>30 days</time_frame>
        <population>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. No data were collected for Outcome Measures</population>
        <group_list>
          <group group_id="O1">
            <title>Biopsy With Lumason</title>
            <description>Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy;</description>
          </group>
          <group group_id="O2">
            <title>Biopsy With Placebos</title>
            <description>Placebos injected prior to ultrasound-guided biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>Complication Rate</title>
          <description>Complication will be defined as 1) bleeding seen on post-biopsy CT or US, 2) drop in hemoglobin of more than 1.5 g/dL within one week after biopsy, or 3) need for hepatic artery embolization.</description>
          <population>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. No data were collected for Outcome Measures</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Success Rate</title>
        <description>Biopsy sample being sufficient for histological diagnosis and/or complete genotyping.</description>
        <time_frame>30 days</time_frame>
        <population>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. No data were collected for Outcome Measures</population>
        <group_list>
          <group group_id="O1">
            <title>Biopsy With Lumason</title>
            <description>Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy;</description>
          </group>
          <group group_id="O2">
            <title>Biopsy With Placebos</title>
            <description>Placebos injected prior to ultrasound-guided biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>Success Rate</title>
          <description>Biopsy sample being sufficient for histological diagnosis and/or complete genotyping.</description>
          <population>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. No data were collected for Outcome Measures</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Insufficient patient recruitment and following internal IRB audit study was abandoned.</time_frame>
      <desc>Insufficient patient recruitment and following internal IRB audit study was abandoned/terminated. The PI has left the institution and no information is available regarding Adverse Events</desc>
      <group_list>
        <group group_id="E1">
          <title>Biopsy With Lumason</title>
          <description>Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy;</description>
        </group>
        <group group_id="E2">
          <title>Biopsy With Placebos</title>
          <description>Placebos injected prior to ultrasound-guided biopsy.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Insufficient patient recruitment and data was lost following departure of key study personnel</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jordan Swensson ,MD</name_or_title>
      <organization>Indiana University Department of Radiology</organization>
      <phone>317-944-1831</phone>
      <email>jswensso@iupui.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03040323
org study id: 1609504711
nct id: NCT03040323
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The investigators plan to compare complication and success rates between two methods of
      ultrasound guidance for biopsy of liver lesions, contrast-enhanced and the current protocol
      without contrast.
As a major oncology and hepatology center, the investigators perform about 3-5 guided
      biopsies for liver tumors weekly. Ultrasound is the preferred modality for imaging biopsies
      due to its ability to visualize and position the biopsy needle in real time with high
      accuracy and safety, is nonionizing, and is quicker compared to other techniques, especially
      CT-guided biopsies. The failure rate of ultrasound guided liver biopsies (including cases
      where biopsy was declined to be performed due to lack of lesion visibility) is about 10%. By
      comparison, in the investigators' practice genotyping of metastatic tumors, with multiple
      core biopsies, is often requested for entry into oncology trials, and failure of tumor
      genotyping after biopsy is estimated to be about 30%.

      Recently, the first ultrasound contrast agent was FDA-approved for characterization of liver
      lesions [sulfur hexafluoride lipid-type A microspheres (Lumason, Bracco Diagnostics, Monroe
      Township, NJ)]. The microbubble agent is deemed safe, including in cardiac failure patients
      and those with chronic airway obstruction. Injecting microbubbles may allow better
      visualization of lesions and adjacent vasculature by enhancing the microvasculature and
      adjacent vessels and potentially reduce incidence of failed biopsy or bleeding complications.
      In addition, determination of necrotic regions in a lesion may allow better direction of
      biopsy.

      Yet there is limited literature on the use of ultrasound contrast agents for improving
      targeted liver biopsies. The investigators intend to prospectively assess the non-diagnostic
      biopsy and complication rates in a group of patients who undergo contrast-enhanced
      ultrasonography (CEUS) using microbubbles at the time of biopsy. The investigators will then
      compare the results from this group with the failure and complication rate from a control
      group of patients undergoing the standard US-guided biopsy procedure. Over 12 months the
      investigators expect to perform approximately 200 biopsies. Power analysis suggests that 125
      patients in both contrast-enhanced sonography and control groups, each, are required. The
      investigators should be able to enroll sufficient patients in 18 months
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Two interventional arms, selected by day of month; 1) biopsy with Lumason, 2) biopsy with placebos
primary purpose: Diagnostic
masking: Single (Participant)
masking description: Patients will not be informed of diagnostic arm.
measure: Complication Rate
time frame: 30 days
description: Complication will be defined as 1) bleeding seen on post-biopsy CT or US, 2) drop in hemoglobin of more than 1.5 g/dL within one week after biopsy, or 3) need for hepatic artery embolization.
measure: Success Rate
time frame: 30 days
description: Biopsy sample being sufficient for histological diagnosis and/or complete genotyping.
arm group label: biopsy with Lumason
arm group type: Experimental
description: liver biopsy performed with prior contrast enhancement with Lumason 60.7Mg Powder for Injection (experimental method)
arm group label: biopsy with placebos
arm group type: Placebo Comparator
description: liver biopsy performed without prior contrast enhancement (standard method)
intervention type: Drug
intervention name: Lumason 60.7Mg Powder for Injection
description: Lumason 60.7Mg Powder for Injection injected prior to ultrasound-guided biopsy
arm group label: biopsy with Lumason
other name: Lumason
intervention type: Drug
intervention name: Placebos
description: Placebos injected prior to ultrasound-guided biopsy
arm group label: biopsy with placebos
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kumar Sandrasegaran, MD
role: Principal Investigator
affiliation: Indiana University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Jordan K. Swensson
investigator title: Assistant Professor Clinical Radiology
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Insufficient patient recruitment and data was lost following departure of key study personnel
point of contact: 