<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/NCT03808324</url>
  </required_header>
  <id_info>
    <org_study_id>AVALON</org_study_id>
    <nct_id>NCT03808324</nct_id>
  </id_info>
  <brief_title>Heart Failure After Heart Transplantation Due to Chronic Rejection</brief_title>
  <acronym>AVALON</acronym>
  <official_title>Allograft Vasculopathy and Unexplained Graft Dysfunction During Long-term Follow-up After Heart Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sahlgrenska University Hospital, Sweden</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate the prevalence of allograft vasculopathy and unexplained graft&#xD;
      dysfunction during long-term follow-up after heart transplantation. Risk factors as well&#xD;
      diagnostic approaches will be investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During long-term follow-up heart transplant recipients are at risk of developing different&#xD;
      complications that are likely to affect quality of life and survival. The most common cause&#xD;
      of death during the later stages after heart transplantation is cardiac allograft&#xD;
      vasculopathy, followed by unexplained graft dysfunction. In this study, advanced imaging&#xD;
      techniques will be used to describe the frequency of these two complications, examine&#xD;
      possible risk factors and study consequences on functional capacity and quality of life.&#xD;
      Further, the investigators will investigate whether it is feasible to screen for these&#xD;
      conditions with non-invasive imaging methods. By studying patients that have performed&#xD;
      cardiac transplantation between 10 and 20 years ago, the investigators expect to have a&#xD;
      significant proportion of patients with these pathological conditions. Methods that will be&#xD;
      used include cardiac magnetic resonance imaging, coronary flow velocity reserve assessment,&#xD;
      right heart catheterization and coronary imaging with angiography and optical coherence&#xD;
      tomography.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">January 2019</start_date>
  <completion_date type="Anticipated">March 2021</completion_date>
  <primary_completion_date type="Anticipated">January 2021</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Degree of stenosis in coronary arteries</measure>
    <time_frame>4 hours</time_frame>
    <description>Coronary angiography gives information about the degree of stenosis in the coronary arteries. In connection with the angiography Optical Coherence Tomography (OCT) will be performed. A precise measurement and characterization of the intima can be performed by OCT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Restrictive allograft hemodynamics</measure>
    <time_frame>2 hours</time_frame>
    <description>Right heart catheterization will be performed using a Swan-Ganz pulmonary artery thermodilution catheter. Right atrial pressure (RAP), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP) and mean arterial pressure (MAP). Cardiac output (CO) and cardiac index (CI) will be recorded by thermodilution. The transpulmonary gradient (TPG) is obtained by subtracting PCWP from MPAP and PVR (in Wood units (WU) by dividing TPG by CO. Measurement will be performed both at rest and after supine bicycle exercise. A restrictive allograft filling pattern will be defined as PCW at rest exceeding 15 mmHg and/or exceeding 25 mmHg during exercise.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Functional assessment of the microvasculature</measure>
    <time_frame>2 hours</time_frame>
    <description>Coronary flow reserve (CRF) measurements may provide functional assessment of the microvasculature. Coronary blood flow velocity (CBFV) is measured in the left anterior descending coronary artery (LAD) before, and during constant adenosine infusion using conventional color Doppler ultrasound equipped with coronary imaging protocol. Mid-distal LAD segment is visualized using high frequency color Doppler (&gt;3 MHz) in the anterior interventricular sulcus. A CINE-loop is then stored to document the 2-D image of LAD. Thereafter spectral Doppler is used to record CBFV. Mean diastolic flow velocity is calculated by manually tracing the diastolic flow velocity signal. Baseline CBFV values are calculated using the mean value of three representative heart beats during resting condition. The mean hyperemic CBFV is calculated as the mean of the three highest CBFV values recorded during the whole infusion period. The ratio between hyperemic and baseline CBFV is defined as CFR.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Degree of myocardial fibrosis</measure>
    <time_frame>4 hours</time_frame>
    <description>Measurement of myocardial T1 times (T1 mapping) with gadolinium-enhanced inversion recovery-prepared sequences may depict diffuse myocardial fibrosis and has good correlation with ex vivo fibrosis content. T1 mapping calculates myocardial T1 relaxation times with image-based signal intensities and will be performed with standard cardiac MR imagers and radiologic workstations.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Cardiac Allograft Vasculopathy</condition>
  <condition>Chronic Rejection of Cardiac Transplant</condition>
  <condition>Graft Dysfunction</condition>
  <arm_group>
    <arm_group_label>Heart transplant recipients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Diagnostic investigations</intervention_name>
    <description>Participants will undergo tests and diagnostics investigations to identify signs of chronic rejection after heart transplantation.</description>
    <arm_group_label>Heart transplant recipients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Heart transplant performed more than 10 years and less than 21 years ago&#xD;
&#xD;
          -  Scheduled yearly post-transplant control&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Estimated GFR &lt; 30 mL/min/1,73m2&#xD;
&#xD;
          -  Radiographic contrast allergy&#xD;
&#xD;
          -  Severe asthma or COLD with FEV1 &lt; 50%&#xD;
&#xD;
          -  Second or third degree AV block&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  In the Investigator's opinion, the patient has a clinically significant disease that&#xD;
             could be adversely affected by study participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Gothenburg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sorosh Esmaily, MD</last_name>
      <phone>+46707488821</phone>
      <email>sorosh.esmaily@gu.se</email>
    </contact>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 29, 2018</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sahlgrenska University Hospital, Sweden</investigator_affiliation>
    <investigator_full_name>Sorosh Esmaily</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03808324
org study id: AVALON
nct id: NCT03808324
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will investigate the prevalence of allograft vasculopathy and unexplained graft
      dysfunction during long-term follow-up after heart transplantation. Risk factors as well
      diagnostic approaches will be investigated.
During long-term follow-up heart transplant recipients are at risk of developing different
      complications that are likely to affect quality of life and survival. The most common cause
      of death during the later stages after heart transplantation is cardiac allograft
      vasculopathy, followed by unexplained graft dysfunction. In this study, advanced imaging
      techniques will be used to describe the frequency of these two complications, examine
      possible risk factors and study consequences on functional capacity and quality of life.
      Further, the investigators will investigate whether it is feasible to screen for these
      conditions with non-invasive imaging methods. By studying patients that have performed
      cardiac transplantation between 10 and 20 years ago, the investigators expect to have a
      significant proportion of patients with these pathological conditions. Methods that will be
      used include cardiac magnetic resonance imaging, coronary flow velocity reserve assessment,
      right heart catheterization and coronary imaging with angiography and optical coherence
      tomography.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Degree of stenosis in coronary arteries
time frame: 4 hours
description: Coronary angiography gives information about the degree of stenosis in the coronary arteries. In connection with the angiography Optical Coherence Tomography (OCT) will be performed. A precise measurement and characterization of the intima can be performed by OCT.
measure: Restrictive allograft hemodynamics
time frame: 2 hours
description: Right heart catheterization will be performed using a Swan-Ganz pulmonary artery thermodilution catheter. Right atrial pressure (RAP), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP) and mean arterial pressure (MAP). Cardiac output (CO) and cardiac index (CI) will be recorded by thermodilution. The transpulmonary gradient (TPG) is obtained by subtracting PCWP from MPAP and PVR (in Wood units (WU) by dividing TPG by CO. Measurement will be performed both at rest and after supine bicycle exercise. A restrictive allograft filling pattern will be defined as PCW at rest exceeding 15 mmHg and/or exceeding 25 mmHg during exercise.
measure: Functional assessment of the microvasculature
time frame: 2 hours
description: Coronary flow reserve (CRF) measurements may provide functional assessment of the microvasculature. Coronary blood flow velocity (CBFV) is measured in the left anterior descending coronary artery (LAD) before, and during constant adenosine infusion using conventional color Doppler ultrasound equipped with coronary imaging protocol. Mid-distal LAD segment is visualized using high frequency color Doppler (>3 MHz) in the anterior interventricular sulcus. A CINE-loop is then stored to document the 2-D image of LAD. Thereafter spectral Doppler is used to record CBFV. Mean diastolic flow velocity is calculated by manually tracing the diastolic flow velocity signal. Baseline CBFV values are calculated using the mean value of three representative heart beats during resting condition. The mean hyperemic CBFV is calculated as the mean of the three highest CBFV values recorded during the whole infusion period. The ratio between hyperemic and baseline CBFV is defined as CFR.
measure: Degree of myocardial fibrosis
time frame: 4 hours
description: Measurement of myocardial T1 times (T1 mapping) with gadolinium-enhanced inversion recovery-prepared sequences may depict diffuse myocardial fibrosis and has good correlation with ex vivo fibrosis content. T1 mapping calculates myocardial T1 relaxation times with image-based signal intensities and will be performed with standard cardiac MR imagers and radiologic workstations.
arm group label: Heart transplant recipients
arm group type: Experimental
intervention type: Diagnostic Test
intervention name: Diagnostic investigations
description: Participants will undergo tests and diagnostics investigations to identify signs of chronic rejection after heart transplantation.
arm group label: Heart transplant recipients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Sahlgrenska University Hospital, Sweden
investigator full name: Sorosh Esmaily
investigator title: Principal Investigator
mesh term: Vascular Diseases
sharing ipd: No