<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/NCT02248831</url>
  </required_header>
  <id_info>
    <org_study_id>DOP19</org_study_id>
    <nct_id>NCT02248831</nct_id>
  </id_info>
  <brief_title>Evaluation of Cardiopulmonary Diseases by Ultrasound</brief_title>
  <official_title>Non-invasive Evaluation of Cardiopulmonary Diseases Using Transthoracic Parametric Doppler Based Assessment of Lung Doppler Signals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Echosense Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Echosense Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Historically, ultrasound imaging of the lung parenchyma has been challenging because of the&#xD;
      high total ultrasound energy attenuation and scattering by the air in the lungs. However,&#xD;
      recent technological advancements have allowed for rapid assessment of various pulmonary&#xD;
      diseases via the use of lung ultrasound. Furthermore, it has been shown that clear&#xD;
      reproducible Doppler signals can be recorded from the lung parenchyma by means of a pulsed&#xD;
      Doppler ultrasound system incorporating a special signal-processing package.&#xD;
&#xD;
      The LDS may contain information of significant diagnostic and physiological value regarding&#xD;
      the pulmonary parenchyma and vasculature, as well as the cardio-vascular system in general.&#xD;
      In a pilot clinical validation study of patients with acute decompensated heart failure&#xD;
      (ADHF) patients, LDS signals unique to ADHF patients were identified, that superpose on the&#xD;
      normal Lung Doppler Signals (unpublished data). These are high velocity &quot;disorganized&quot;&#xD;
      variable signals that are not synchronous with the cardiac cycle but rather sometimes with&#xD;
      respiration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Purpose and Rationale&#xD;
&#xD;
      The purpose of this study is to assess the utility of noninvasive assessment of lung Doppler&#xD;
      signals performed via transthoracic parametric Doppler. The study has two major objectives&#xD;
      and is thus, divided into two phases, which are on a continuum.&#xD;
&#xD;
      Phase 1: The objective is to further evaluate LDS among patients presenting to the emergency&#xD;
      department with acute dyspnea, in order to determine the diagnostic value of this&#xD;
      non-invasive method to distinguish cardiac from pulmonary causes of dyspnea.&#xD;
&#xD;
      Phase 2: In addition, for those patients admitted to the hospital with a clinical diagnosis&#xD;
      of ADHF, we would like to further characterize changes in daily lung Doppler signal as a&#xD;
      surrogate biomarker of intravascular volume status, as assessed by clinical assessment.&#xD;
&#xD;
      Study Design and Methods:&#xD;
&#xD;
      1. Overall study design&#xD;
&#xD;
      Phase 1:&#xD;
&#xD;
      Prospective cohort study of patients presenting to the Massachusetts General Hospital&#xD;
      emergency department with acute dyspnea. . In addition, at MGH, pts admitted to the cardiac&#xD;
      floors (Ellison 9, 10, 11) and general medicine floors (White 9, 10, 11) with an admitting&#xD;
      diagnosis of heart failure, who presented with acute dyspnea, will be approached for&#xD;
      enrollment within 24 hours of hospital admission. All patients with acute dyspnea will&#xD;
      undergo routine clinical assessment, laboratory testing, and diagnostic imaging. In addition,&#xD;
      all patients will also undergo transthoracic parametric Doppler ultrasound based assessment&#xD;
      of LDS. Patients will be treated as usual, under the direction of the attending physician.&#xD;
      Two independent cardiologists will perform detailed chart review on all patients to determine&#xD;
      the etiology of acute dyspnea. They will be blinded to the results of the LDS. In the event&#xD;
      of discrepant findings, a third cardiologist will perform a final detailed chart review to&#xD;
      adjudicate the diagnosis.&#xD;
&#xD;
      Additionally, radiologist employed at MGH and who are independent to the study may perform&#xD;
      blinded adjudication of the study participants' chest x-rays (CXR) obtained in the Emergency&#xD;
      Department on the day of enrollment into the study&#xD;
&#xD;
      Phase 2:&#xD;
&#xD;
      In addition, patients diagnosed with ADHF (diagnosed based on the criteria described below),&#xD;
      will undergo daily TPD and assessment of LDS to further characterize changes in LDS over&#xD;
      time, until the day of discharge or up to day 7 of hospitalization, whichever comes first. In&#xD;
      addition to the initial inpatient scans, study staff will try to acquire a final scan within&#xD;
      72 hours of discharge for patients diagnosed with ADHF, regardless of the day of&#xD;
      hospitalization. This cohort of patients will also undergo daily clinical assessment of&#xD;
      volume status, weight measurement, and BNP assessment. In the event that repeat BNP or&#xD;
      NT-proBNP labs have not been drawn within 72 hours of discharge, study staff will coordinate&#xD;
      with the pathology laboratory (Dr. Kent Lewandrowski) to perform the assay as a research test&#xD;
      using excess clinical specimen from the subject's routine clinical blood draw if available.&#xD;
      Research subjects will not be charged for the cost of the BNP or NT-Pro-BNP assay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">May 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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients identified with COPD (or CHF) in comparison to physician diagnosis</measure>
    <time_frame>1y</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identify changes in lung doppler signals according to the clinical status over few days in comparison to the physician diagnosis</measure>
    <time_frame>1y</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">600</enrollment>
  <condition>Dyspnea</condition>
  <condition>Acute Decompensated Heart Failure</condition>
  <arm_group>
    <arm_group_label>Doppler ultrasound</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Using ultrasound noninvasively and recording Doppler signals from the right chest wall</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Recording Doppler ultrasound signals noninvasively</intervention_name>
    <description>Using ultrasound noninvasively and recording Doppler signals from the right chest wall</description>
    <arm_group_label>Doppler ultrasound</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Phase 1(ED):&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
        Age &gt; 18 years Acute onset dyspnea&#xD;
&#xD;
          -  Phase 2 (Inpatient):&#xD;
&#xD;
        Age &gt; 18 years Acute onset dyspnea: defined as SOB at rest or with minimal activity, with&#xD;
        onset within the past 14 days PLUS&#xD;
&#xD;
        The following criteria are required to be classified as heart failure (event has to meet&#xD;
        all of the following criteria):&#xD;
&#xD;
        a) The patient exhibits documented new or worsening symptoms due to heart failure on&#xD;
        presentation, including at least one of the following: i) Dyspnea (dyspnea with exertion,&#xD;
        dyspnea at rest, orthopnea) ii) Decreased exercise tolerance b) The patient has objective&#xD;
        evidence of new or worsening heart failure, consisting of at least two physical exam&#xD;
        findings (or one physical exam finding and one diagnostic criterion) including: i) Physical&#xD;
        exam findings considered to be due to heart failure, including new or worsened:&#xD;
&#xD;
        (1) Peripheral edema (2) Increasing abdominal distention or ascites (in the absence of&#xD;
        primary hepatic disease) (3) Increased jugular venous pressure and/or hepatojugular reflux&#xD;
        (4) Rapid weight gain thought to be related to fluid overload ii) Diagnostic findings&#xD;
        considered to be due to heart failure, including new or worsened:&#xD;
&#xD;
          1. Increased B-type natriuretic peptide/ NT-proBNP concentrations consistent with&#xD;
             decompensation of heart failure Note: In patients with chronically elevated&#xD;
             natriuretic peptides, a significant increase should be noted above baseline.&#xD;
&#xD;
          2. Radiological evidence of pulmonary congestion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Phase 1 (ED):&#xD;
&#xD;
        Pregnant women Inability to consent&#xD;
&#xD;
          -  Phase 2 (Inpatient):&#xD;
&#xD;
        Pregnant women Pneumonia - currently, or within the past 30 days Non-cardiogenic pulmonary&#xD;
        edema (e.g. ARDS) Interstitial lung disease Inability to 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_official>
    <last_name>Maulik Majmudar, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>MGH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emergency Medicine department and Inpatients floors,MGH</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>February 7, 2019</last_update_submitted>
  <last_update_submitted_qc>February 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dyspnea</keyword>
  <keyword>Acute decompensated heart failure</keyword>
  <keyword>Doppler ultrasound</keyword>
  <keyword>Lung Doppler signals</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyspnea</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Pulmonary Heart Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT02248831
org study id: DOP19
nct id: NCT02248831
lead sponsor: 
collaborator: 
has dmc: No
Historically, ultrasound imaging of the lung parenchyma has been challenging because of the
      high total ultrasound energy attenuation and scattering by the air in the lungs. However,
      recent technological advancements have allowed for rapid assessment of various pulmonary
      diseases via the use of lung ultrasound. Furthermore, it has been shown that clear
      reproducible Doppler signals can be recorded from the lung parenchyma by means of a pulsed
      Doppler ultrasound system incorporating a special signal-processing package.

      The LDS may contain information of significant diagnostic and physiological value regarding
      the pulmonary parenchyma and vasculature, as well as the cardio-vascular system in general.
      In a pilot clinical validation study of patients with acute decompensated heart failure
      (ADHF) patients, LDS signals unique to ADHF patients were identified, that superpose on the
      normal Lung Doppler Signals (unpublished data). These are high velocity "disorganized"
      variable signals that are not synchronous with the cardiac cycle but rather sometimes with
      respiration.
Study Purpose and Rationale

      The purpose of this study is to assess the utility of noninvasive assessment of lung Doppler
      signals performed via transthoracic parametric Doppler. The study has two major objectives
      and is thus, divided into two phases, which are on a continuum.

      Phase 1: The objective is to further evaluate LDS among patients presenting to the emergency
      department with acute dyspnea, in order to determine the diagnostic value of this
      non-invasive method to distinguish cardiac from pulmonary causes of dyspnea.

      Phase 2: In addition, for those patients admitted to the hospital with a clinical diagnosis
      of ADHF, we would like to further characterize changes in daily lung Doppler signal as a
      surrogate biomarker of intravascular volume status, as assessed by clinical assessment.

      Study Design and Methods:

      1. Overall study design

      Phase 1:

      Prospective cohort study of patients presenting to the Massachusetts General Hospital
      emergency department with acute dyspnea. . In addition, at MGH, pts admitted to the cardiac
      floors (Ellison 9, 10, 11) and general medicine floors (White 9, 10, 11) with an admitting
      diagnosis of heart failure, who presented with acute dyspnea, will be approached for
      enrollment within 24 hours of hospital admission. All patients with acute dyspnea will
      undergo routine clinical assessment, laboratory testing, and diagnostic imaging. In addition,
      all patients will also undergo transthoracic parametric Doppler ultrasound based assessment
      of LDS. Patients will be treated as usual, under the direction of the attending physician.
      Two independent cardiologists will perform detailed chart review on all patients to determine
      the etiology of acute dyspnea. They will be blinded to the results of the LDS. In the event
      of discrepant findings, a third cardiologist will perform a final detailed chart review to
      adjudicate the diagnosis.

      Additionally, radiologist employed at MGH and who are independent to the study may perform
      blinded adjudication of the study participants' chest x-rays (CXR) obtained in the Emergency
      Department on the day of enrollment into the study

      Phase 2:

      In addition, patients diagnosed with ADHF (diagnosed based on the criteria described below),
      will undergo daily TPD and assessment of LDS to further characterize changes in LDS over
      time, until the day of discharge or up to day 7 of hospitalization, whichever comes first. In
      addition to the initial inpatient scans, study staff will try to acquire a final scan within
      72 hours of discharge for patients diagnosed with ADHF, regardless of the day of
      hospitalization. This cohort of patients will also undergo daily clinical assessment of
      volume status, weight measurement, and BNP assessment. In the event that repeat BNP or
      NT-proBNP labs have not been drawn within 72 hours of discharge, study staff will coordinate
      with the pathology laboratory (Dr. Kent Lewandrowski) to perform the assay as a research test
      using excess clinical specimen from the subject's routine clinical blood draw if available.
      Research subjects will not be charged for the cost of the BNP or NT-Pro-BNP assay.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Number of patients identified with COPD (or CHF) in comparison to physician diagnosis
time frame: 1y
measure: Identify changes in lung doppler signals according to the clinical status over few days in comparison to the physician diagnosis
time frame: 1y
arm group label: Doppler ultrasound
arm group type: Experimental
description: Using ultrasound noninvasively and recording Doppler signals from the right chest wall
intervention type: Device
intervention name: Recording Doppler ultrasound signals noninvasively
description: Using ultrasound noninvasively and recording Doppler signals from the right chest wall
arm group label: Doppler ultrasound
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maulik Majmudar, Dr
role: Principal Investigator
affiliation: MGH
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dyspnea
mesh term: Heart Failure
mesh term: Pulmonary Heart Disease