<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/NCT03245255</url>
  </required_header>
  <id_info>
    <org_study_id>R21HL130899</org_study_id>
    <secondary_id>R21HL130899</secondary_id>
    <nct_id>NCT03245255</nct_id>
  </id_info>
  <brief_title>Noninvasive Real-time Intracardiac Pressure Measurements Using Subharmonic Ultrasound</brief_title>
  <official_title>Noninvasive Real-time Intracardiac Pressure Measurements Using Subharmonic Ultrasound</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>GE Healthcare</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will use contrast echocardiography to assess the accuracy of a new non-invasive&#xD;
      imaging method for subharmonic aided pressure estimation (SHAPE) compared to simultaneously&#xD;
      acquired intra-cardiac pressures measured invasively during cardiac catheterization. This&#xD;
      study is designed to verify that contrast echocardiography using the SHAPE method, already&#xD;
      proven in a canine model and tested in a human pilot study can be used as a surrogate for&#xD;
      cardiac catheterization with sufficient accuracy to allow clinical applicability in humans.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2017</start_date>
  <completion_date type="Actual">September 18, 2020</completion_date>
  <primary_completion_date type="Actual">September 18, 2020</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>
  <primary_outcome>
    <measure>Accuracy of ventricular relaxation rate and relaxation time constant</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">80</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>Sonazoid for pressure measurements</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% sodium chloride solution infused at a rate of at least 2 ml/min.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sonazoid</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 Sonazoid 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>Sonazoid for pressure measurements</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be scheduled for cardiac catheterization procedure.&#xD;
&#xD;
          -  Be at least 18 years of age.&#xD;
&#xD;
          -  Be medically stable.&#xD;
&#xD;
          -  If a female of child-bearing potential, must have a negative pregnancy test.&#xD;
&#xD;
          -  Be conscious and able to comply with study procedures.&#xD;
&#xD;
          -  Have signed Informed Consent to participate in the study.&#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;
          -  Females who are pregnant or nursing.&#xD;
&#xD;
          -  Patients not scheduled for cardiac catheterization procedure.&#xD;
&#xD;
          -  Patients who have received an investigational drug in the 30 days before, or will&#xD;
             receive one within 72 h after, study drug administration.&#xD;
&#xD;
          -  Patients currently on chemotherapy or with other primary cancers requiring treatment.&#xD;
&#xD;
          -  Patients who are medically unstable, patients who are seriously or terminally ill, and&#xD;
             patients whose clinical course is unpredictable.&#xD;
&#xD;
          -  Patients with a history of anaphylactic allergy to eggs or egg products, manifested by&#xD;
             one or more of the following symptoms: generalised urticaria, difficulty in breathing,&#xD;
             swelling of the mouth and throat, hypotension, or shock. (Subjects with&#xD;
             nonanaphylactic allergies to eggs or egg products may be enrolled in the study, but&#xD;
             must be watched carefully for 1 h following the administration of SONAZOID).&#xD;
&#xD;
          -  Patients with congenital heart defects.&#xD;
&#xD;
          -  Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary&#xD;
             emboli.&#xD;
&#xD;
          -  Patients with respiratory distress syndrome or a contraindication to pharmacological&#xD;
             vasodilator stress agents.&#xD;
&#xD;
          -  Patients with thrombosis within the hepatic, portal, or mesenteric veins.&#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 K 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>September 2020</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>September 21, 2020</last_update_submitted>
  <last_update_submitted_qc>September 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>2018-08-01 (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 15, 2021</submitted>
    <returned>January 14, 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/NCT03245255
org study id: R21HL130899
secondary id: R21HL130899
nct id: NCT03245255
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will use contrast echocardiography to assess the accuracy of a new non-invasive
      imaging method for subharmonic aided pressure estimation (SHAPE) compared to simultaneously
      acquired intra-cardiac 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
measure: Accuracy of ventricular relaxation rate and relaxation time constant
time frame: up to 1 day
description: ANOVA/Post-hoc comparisons
arm group label: Sonazoid for pressure measurements
arm group type: Experimental
description: 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% sodium chloride solution infused at a rate of at least 2 ml/min.
intervention type: Drug
intervention name: Sonazoid
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 Sonazoid 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: Sonazoid for pressure measurements
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Jaydev K 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: Sponsor
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: Clinical Study Report (CSR)
ipd time frame: 2018-08-01 (anticipated) or starting 6 months after publication
ipd access criteria: Accessible research platform
submitted: December 15, 2021
returned: January 14, 2022