<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/NCT03231371</url>
  </required_header>
  <id_info>
    <org_study_id>HUM23585</org_study_id>
    <nct_id>NCT03231371</nct_id>
  </id_info>
  <brief_title>Coronary Artery Vasculopathy in Pediatric Heart Transplant Patients</brief_title>
  <acronym>CFR-OHT</acronym>
  <official_title>Early Detection of Coronary Artery Vasculopathy in Pediatric Heart Transplant Patients: A Prospective Assessment Using Coronary Flow Reserve and Contrast-Enhanced Cardiac MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bryan Goldstein</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Heart transplantation is a life-sustaining therapy that allows patients with either&#xD;
      congenital or acquired heart disease and severe cardiac dysfunction to survive. Over time,&#xD;
      however, the transplanted heart can develop problems. One of the more common and troubling&#xD;
      problems is the development of stenoses, or narrowings, within the coronary arteries. These&#xD;
      narrowings, technically referred to as coronary artery vasculopathy (CAV for short), account&#xD;
      for the single most common cause of death or need for repeat heart transplant in persons more&#xD;
      than one year post-transplant. Traditionally, CAV has been diagnosed at cardiac&#xD;
      catheterization using coronary angiography (where dye is directly injected into the coronary&#xD;
      blood vessels and viewed using special x-ray equipment called fluoroscopy). There is no good&#xD;
      treatment for CAV aside from treatment of symptoms and listing for repeat heart&#xD;
      transplantation. The goal of this study is to test several newer methods of diagnosing CAV.&#xD;
      The first is called coronary flow reserve (catheterization test). The second is called&#xD;
      Endo-PAT (a finger probe test) and the third is called contrast-enhanced cardiac MRI (MRI&#xD;
      test, only for patients 12 and older). The older method (coronary angiography) will still be&#xD;
      used in all cases, in addition to the new tests The goal is, one day, to be able to diagnose&#xD;
      patients with CAV earlier in the course, prior to a patient's development of abnormal&#xD;
      angiograms. If this can be done, it is possible that better therapies will be able to be used&#xD;
      to stop or even reverse the development of CAV, perhaps reducing, or at least delaying, the&#xD;
      need for repeat heart transplantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2008</start_date>
  <completion_date type="Actual">January 2011</completion_date>
  <primary_completion_date type="Actual">January 2011</primary_completion_date>
  <phase>Phase 3</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>Coronary Flow Reserve (CFR)</measure>
    <time_frame>Baseline testing (acute only), 3 minutes of adenosine infusion</time_frame>
    <description>Ratio of peak to baseline coronary flow velocity (CFV)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gadolinium Enhancement by Cardiac MRI</measure>
    <time_frame>Baseline MRI only</time_frame>
    <description>Categorical measure - yes or no; number of participants with gadolinium enhancement</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Orthotopic Heart Transplant</condition>
  <arm_group>
    <arm_group_label>Study Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adenosine</intervention_name>
    <description>Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).</description>
    <arm_group_label>Study Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients age 1 - 25 years who are status-post OHT (≤18 years at the time of&#xD;
             transplantation) and undergoing routine post-transplant surveillance catheterization&#xD;
             for endomyocardial biopsy and coronary angiography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The presence of sick sinus syndrome or 2nd or 3rd degree atrioventricular block&#xD;
             (without a functioning implanted pacemaker)&#xD;
&#xD;
          -  Hemodynamically significant valvular disease&#xD;
&#xD;
          -  Severe asthma or bronchospasm, known severe CAV&#xD;
&#xD;
          -  Pulmonary hypertension.&#xD;
&#xD;
          -  Patients taking digoxin&#xD;
&#xD;
          -  Verapamil and dipyridamole are also excluded given known interactions with adenosine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bryan Goldstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of MIchigan-Congenital Heart Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>October 19, 2011</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <results_first_submitted>August 29, 2017</results_first_submitted>
  <results_first_submitted_qc>August 29, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">September 26, 2017</results_first_posted>
  <last_update_submitted>August 29, 2017</last_update_submitted>
  <last_update_submitted_qc>August 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Bryan Goldstein</investigator_full_name>
    <investigator_title>Principal Investigator, Clinical Lecturer</investigator_title>
  </responsible_party>
  <keyword>Orthotopic Heart Transplant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenosine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Study Arm</title>
          <description>Adenosine: Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Optional and Age Limited (12 Yrs+) MRI</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>chose or were ineligible to have MRI</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Study Arm</title>
          <description>Adenosine: Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>1-18 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18 - 25 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Coronary Flow Reserve (CFR)</title>
        <description>Ratio of peak to baseline coronary flow velocity (CFV)</description>
        <time_frame>Baseline testing (acute only), 3 minutes of adenosine infusion</time_frame>
        <population>Remaining subjects (of the 21 who completed) had unusable signal data.</population>
        <group_list>
          <group group_id="O1">
            <title>Study Arm</title>
            <description>Adenosine: Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Coronary Flow Reserve (CFR)</title>
          <description>Ratio of peak to baseline coronary flow velocity (CFV)</description>
          <population>Remaining subjects (of the 21 who completed) had unusable signal data.</population>
          <units>ratio: peak to baseline CFV</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.77" spread="2.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gadolinium Enhancement by Cardiac MRI</title>
        <description>Categorical measure - yes or no; number of participants with gadolinium enhancement</description>
        <time_frame>Baseline MRI only</time_frame>
        <population>Only 9 participants had MRI data available. Remaining subjects (of 21) did not undergo MRI performed within study time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>Study Arm</title>
            <description>Adenosine: Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).</description>
          </group>
        </group_list>
        <measure>
          <title>Gadolinium Enhancement by Cardiac MRI</title>
          <description>Categorical measure - yes or no; number of participants with gadolinium enhancement</description>
          <population>Only 9 participants had MRI data available. Remaining subjects (of 21) did not undergo MRI performed within study time frame.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>72 hours post infusion</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Study Arm</title>
          <description>Adenosine: Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Transient Atrial Ventricular block, self-resolved without intervention</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="22"/>
              </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>
    <point_of_contact>
      <name_or_title>Bryan Goldstein</name_or_title>
      <organization>University of Michigan</organization>
      <email>Bryan.Goldstein@cchmc.org</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/NCT03231371
org study id: HUM23585
nct id: NCT03231371
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Heart transplantation is a life-sustaining therapy that allows patients with either
      congenital or acquired heart disease and severe cardiac dysfunction to survive. Over time,
      however, the transplanted heart can develop problems. One of the more common and troubling
      problems is the development of stenoses, or narrowings, within the coronary arteries. These
      narrowings, technically referred to as coronary artery vasculopathy (CAV for short), account
      for the single most common cause of death or need for repeat heart transplant in persons more
      than one year post-transplant. Traditionally, CAV has been diagnosed at cardiac
      catheterization using coronary angiography (where dye is directly injected into the coronary
      blood vessels and viewed using special x-ray equipment called fluoroscopy). There is no good
      treatment for CAV aside from treatment of symptoms and listing for repeat heart
      transplantation. The goal of this study is to test several newer methods of diagnosing CAV.
      The first is called coronary flow reserve (catheterization test). The second is called
      Endo-PAT (a finger probe test) and the third is called contrast-enhanced cardiac MRI (MRI
      test, only for patients 12 and older). The older method (coronary angiography) will still be
      used in all cases, in addition to the new tests The goal is, one day, to be able to diagnose
      patients with CAV earlier in the course, prior to a patient's development of abnormal
      angiograms. If this can be done, it is possible that better therapies will be able to be used
      to stop or even reverse the development of CAV, perhaps reducing, or at least delaying, the
      need for repeat heart transplantation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Coronary Flow Reserve (CFR)
time frame: Baseline testing (acute only), 3 minutes of adenosine infusion
description: Ratio of peak to baseline coronary flow velocity (CFV)
measure: Gadolinium Enhancement by Cardiac MRI
time frame: Baseline MRI only
description: Categorical measure - yes or no; number of participants with gadolinium enhancement
arm group label: Study Arm
arm group type: Experimental
intervention type: Drug
intervention name: Adenosine
description: Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).
arm group label: Study Arm
criteria: 
gender: All
minimum age: 1 Year
maximum age: 25 Years
healthy volunteers: No
last name: Bryan Goldstein, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Michigan
investigator full name: Bryan Goldstein
investigator title: Principal Investigator, Clinical Lecturer
mesh term: Vascular Diseases
mesh term: Adenosine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 