<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/NCT03243942</url>
  </required_header>
  <id_info>
    <org_study_id>15SDG25740015</org_study_id>
    <nct_id>NCT03243942</nct_id>
  </id_info>
  <brief_title>Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement</brief_title>
  <official_title>Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Heart Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lantheus Medical Imaging</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Thomas Jefferson University</source>
  <oversight_info>
    <has_dmc>No</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 fundamental hypothesis of this project is that real-time intracardiac pressures can be&#xD;
      monitored and quantified noninvasively in humans using a novel contrast-enhanced ultrasound&#xD;
      technique called subharmonic-aided pressure estimation (SHAPE).This study will use contrast&#xD;
      echocardiography to assess the accuracy of SHAPE compared to simultaneously acquired&#xD;
      intracardiac pressures measured invasively during cardiac catheterization. This study is&#xD;
      designed to verify that contrast echocardiography using the SHAPE method, already proven in a&#xD;
      canine model and tested in a human pilot study can be used as a surrogate for cardiac&#xD;
      catheterization with sufficient accuracy to allow clinical applicability in humans.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">June 26, 2019</completion_date>
  <primary_completion_date type="Actual">June 26, 2019</primary_completion_date>
  <phase>Phase 2</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Agreement between SHAPE and pressure catheter measurements</measure>
    <time_frame>up to 1 day</time_frame>
    <description>Correlation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Error between SHAPE and pressure catheter measurements</measure>
    <time_frame>up to 1 day</time_frame>
    <description>ANOVA/Post-hoc comparisons</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Cardiac Catheterization</condition>
  <condition>Blood Pressure</condition>
  <condition>Heart Ventricles</condition>
  <condition>Echocardiography</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Definity for pressure measurements</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 vials of activated Definity mixed with 50 ml saline. As per manufacturer's recommendation the infusion rate may vary between 4-10 ml/min (to provide diagnostic intracardiac contrast visibility).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Definity</intervention_name>
    <description>Whenever a patient undergoes cardiac catheterization, which routinely includes intracardiac pressure monitoring using a pressure catheter, as part of their standard clinical care and agrees to participate in the study, we will acquire research data. With Definity infusion, SHAPE algorithm will be initiated to determine optimum acoustic pressure. Then, at the optimum acoustic pressure SHAPE specific data will be acquired from the cardiac chambers and aorta synchronously with the pressures recorded by the catheter (as a part of the patient's standard of care). After acquiring the ultrasound imaging data, the remainder of the heart catheterization will be completed by the attending cardiologist according to the patients' standard of care.</description>
    <arm_group_label>Definity for pressure measurements</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be scheduled for a cardiac catheterization procedure&#xD;
&#xD;
          -  Adult patients over the age of 21&#xD;
&#xD;
          -  Acceptable baseline echocardiographic images in the supine position&#xD;
&#xD;
          -  If a female of child-bearing potential, must have a negative pregnancy test&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically unstable patients, e.g., those who are clinically in decompensated heart&#xD;
             failure or having active chest pain or presenting for admission with an unstable&#xD;
             anginal syndrome&#xD;
&#xD;
          -  Patients in whom introduction of a catheter into the left ventricle is contraindicated&#xD;
             or would potentially be dangerous, e.g., patients with active ventricular arrhythmias&#xD;
             or with significant aortic valve stenosis where crossing the aortic valve may be&#xD;
             difficult and not clinically necessary&#xD;
&#xD;
          -  Patients with anatomic right-to-left, bi-directional, or transient right-to-left&#xD;
             cardiac shunts where Definity could traverse as a bolus&#xD;
&#xD;
          -  Patients with known hypersensitivity to Definity&#xD;
&#xD;
          -  Females who are pregnant or nursing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jaydev Dave</last_name>
    <role>Principal Investigator</role>
    <affiliation>Thomas Jefferson University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Thomas Jefferson University and Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Dave JK, Halldorsdottir VG, Eisenbrey JR, Liu JB, McDonald ME, Dickie K, Leung C, Forsberg F. Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control. 2011 Oct;58(10):2056-66. doi: 10.1109/TUFFC.2011.2056.</citation>
    <PMID>21989870</PMID>
  </reference>
  <reference>
    <citation>Dave JK, Halldorsdottir VG, Eisenbrey JR, Forsberg F. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures. Ultrason Imaging. 2012 Apr;34(2):81-92. doi: 10.1177/016173461203400202.</citation>
    <PMID>22724314</PMID>
  </reference>
  <reference>
    <citation>Dave JK, Halldorsdottir VG, Eisenbrey JR, Merton DA, Liu JB, Machado P, Zhao H, Park S, Dianis S, Chalek CL, Thomenius KE, Brown DB, Forsberg F. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013 Apr;53(4):880-8. doi: 10.1016/j.ultras.2012.12.010. Epub 2013 Jan 2.</citation>
    <PMID>23347593</PMID>
  </reference>
  <reference>
    <citation>Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures. Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H126-32. doi: 10.1152/ajpheart.00560.2011. Epub 2012 May 4.</citation>
    <PMID>22561300</PMID>
  </reference>
  <reference>
    <citation>Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012 Jan;5(1):87-92. doi: 10.1016/j.jcmg.2011.08.017.</citation>
    <PMID>22239898</PMID>
  </reference>
  <reference>
    <citation>Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.</citation>
    <PMID>23525208</PMID>
  </reference>
  <reference>
    <citation>Forsberg F, Liu JB, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005 Apr;52(4):581-3. doi: 10.1109/tuffc.2005.1428040.</citation>
    <PMID>16060506</PMID>
  </reference>
  <reference>
    <citation>Halldorsdottir VG, Dave JK, Leodore LM, Eisenbrey JR, Park S, Hall AL, Thomenius K, Forsberg F. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions. Ultrason Imaging. 2011 Jul;33(3):153-64. doi: 10.1177/016173461103300301.</citation>
    <PMID>21842580</PMID>
  </reference>
  <reference>
    <citation>Shi WT, Forsberg F, Raichlen JS, Needleman L, Goldberg BB. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999 Feb;25(2):275-83. doi: 10.1016/s0301-5629(98)00163-x.</citation>
    <PMID>10320317</PMID>
  </reference>
  <reference>
    <citation>Halldorsdottir VG, Dave JK, Eisenbrey JR, Machado P, Zhao H, Liu JB, Merton DA, Forsberg F. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept. Ultrasonics. 2014 Sep;54(7):1938-44. doi: 10.1016/j.ultras.2014.04.022. Epub 2014 May 6.</citation>
    <PMID>24856899</PMID>
  </reference>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>July 9, 2019</last_update_submitted>
  <last_update_submitted_qc>July 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Thomas Jefferson University</investigator_affiliation>
    <investigator_full_name>Jaydev Dave</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>pressure measurements</keyword>
  <keyword>blood pressure</keyword>
  <keyword>contrast echocardiography</keyword>
  <keyword>ventricular pressures</keyword>
  <keyword>catheterization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>This project will generate pressure values in the aorta, and left and right ventricles using the proposed research method (i.e., SHAPE) and using the standard of care (i.e., catheter based pressure values). Additionally peripheral and central pressures will be generated. All of the pressure values will be made available. Further, all ultrasound data obtained for SHAPE measurements will be made available after anonymizing the data-set to remove any patient information.</ipd_description>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>2019-05-30 (anticipated) or starting 6 months after publication</ipd_time_frame>
    <ipd_access_criteria>Accessible research platform</ipd_access_criteria>
  </patient_data>
  <pending_results>
    <submitted>December 13, 2021</submitted>
    <returned>January 11, 2022</returned>
  </pending_results>
  <!-- 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/NCT03243942
org study id: 15SDG25740015
nct id: NCT03243942
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The fundamental hypothesis of this project is that real-time intracardiac pressures can be
      monitored and quantified noninvasively in humans using a novel contrast-enhanced ultrasound
      technique called subharmonic-aided pressure estimation (SHAPE).This study will use contrast
      echocardiography to assess the accuracy of SHAPE compared to simultaneously acquired
      intracardiac pressures measured invasively during cardiac catheterization. This study is
      designed to verify that contrast echocardiography using the SHAPE method, already proven in a
      canine model and tested in a human pilot study can be used as a surrogate for cardiac
      catheterization with sufficient accuracy to allow clinical applicability in humans.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Agreement between SHAPE and pressure catheter measurements
time frame: up to 1 day
description: Correlation
measure: Error between SHAPE and pressure catheter measurements
time frame: up to 1 day
description: ANOVA/Post-hoc comparisons
arm group label: Definity for pressure measurements
arm group type: Experimental
description: 2 vials of activated Definity mixed with 50 ml saline. As per manufacturer's recommendation the infusion rate may vary between 4-10 ml/min (to provide diagnostic intracardiac contrast visibility).
intervention type: Drug
intervention name: Definity
description: Whenever a patient undergoes cardiac catheterization, which routinely includes intracardiac pressure monitoring using a pressure catheter, as part of their standard clinical care and agrees to participate in the study, we will acquire research data. With Definity infusion, SHAPE algorithm will be initiated to determine optimum acoustic pressure. Then, at the optimum acoustic pressure SHAPE specific data will be acquired from the cardiac chambers and aorta synchronously with the pressures recorded by the catheter (as a part of the patient's standard of care). After acquiring the ultrasound imaging data, the remainder of the heart catheterization will be completed by the attending cardiologist according to the patients' standard of care.
arm group label: Definity for pressure measurements
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Jaydev Dave
role: Principal Investigator
affiliation: Thomas Jefferson University
facility: 
country: United States
citation: Dave JK, Halldorsdottir VG, Eisenbrey JR, Liu JB, McDonald ME, Dickie K, Leung C, Forsberg F. Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control. 2011 Oct;58(10):2056-66. doi: 10.1109/TUFFC.2011.2056.
PMID: 21989870
citation: Dave JK, Halldorsdottir VG, Eisenbrey JR, Forsberg F. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures. Ultrason Imaging. 2012 Apr;34(2):81-92. doi: 10.1177/016173461203400202.
PMID: 22724314
citation: Dave JK, Halldorsdottir VG, Eisenbrey JR, Merton DA, Liu JB, Machado P, Zhao H, Park S, Dianis S, Chalek CL, Thomenius KE, Brown DB, Forsberg F. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013 Apr;53(4):880-8. doi: 10.1016/j.ultras.2012.12.010. Epub 2013 Jan 2.
PMID: 23347593
citation: Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures. Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H126-32. doi: 10.1152/ajpheart.00560.2011. Epub 2012 May 4.
PMID: 22561300
citation: Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012 Jan;5(1):87-92. doi: 10.1016/j.jcmg.2011.08.017.
PMID: 22239898
citation: Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.
PMID: 23525208
citation: Forsberg F, Liu JB, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005 Apr;52(4):581-3. doi: 10.1109/tuffc.2005.1428040.
PMID: 16060506
citation: Halldorsdottir VG, Dave JK, Leodore LM, Eisenbrey JR, Park S, Hall AL, Thomenius K, Forsberg F. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions. Ultrason Imaging. 2011 Jul;33(3):153-64. doi: 10.1177/016173461103300301.
PMID: 21842580
citation: Shi WT, Forsberg F, Raichlen JS, Needleman L, Goldberg BB. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999 Feb;25(2):275-83. doi: 10.1016/s0301-5629(98)00163-x.
PMID: 10320317
citation: Halldorsdottir VG, Dave JK, Eisenbrey JR, Machado P, Zhao H, Liu JB, Merton DA, Forsberg F. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept. Ultrasonics. 2014 Sep;54(7):1938-44. doi: 10.1016/j.ultras.2014.04.022. Epub 2014 May 6.
PMID: 24856899
responsible party type: Principal Investigator
investigator affiliation: Thomas Jefferson University
investigator full name: Jaydev Dave
investigator title: Assistant Professor
mesh term: Heart Failure
sharing ipd: Yes
ipd description: This project will generate pressure values in the aorta, and left and right ventricles using the proposed research method (i.e., SHAPE) and using the standard of care (i.e., catheter based pressure values). Additionally peripheral and central pressures will be generated. All of the pressure values will be made available. Further, all ultrasound data obtained for SHAPE measurements will be made available after anonymizing the data-set to remove any patient information.
ipd info type: Informed Consent Form (ICF)
ipd time frame: 2019-05-30 (anticipated) or starting 6 months after publication
ipd access criteria: Accessible research platform
submitted: December 13, 2021
returned: January 11, 2022