<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/NCT03248674</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-41455</org_study_id>
    <nct_id>NCT03248674</nct_id>
  </id_info>
  <brief_title>Diagnostic Performance of Coronary CT Angiography With CT FFR in Kidney Transplantation Candidates</brief_title>
  <official_title>Diagnostic Performance of Coronary Computed Tomography Angiography With Computed Tomography Fractional Flow Reserve in Kidney Transplantation Candidates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Siemens Medical Solutions</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with chronic kidney disease (CKD) before kidney transplantation require that&#xD;
      obstructive coronary artery disease (CAD) is excluded, as cardiovascular complications are&#xD;
      the leading cause of mortality in kidney transplant patients. However, in this patient&#xD;
      population, the optimal method for the detection of obstructive CAD has not been identified.&#xD;
      Noninvasive stress tests such as Dobutamine stress echocardiography or nuclear perfusion&#xD;
      study have low diagnostic accuracy. CT fractional flow reserve measurement (CT FFR) is a&#xD;
      novel non-invasive (FDA approved) imaging test to identify obstructive CAD. The goal of this&#xD;
      project is to evaluate the diagnostic accuracy of CT FFR in the detection of obstructive&#xD;
      coronary artery disease in patients with chronic kidney disease before kidney&#xD;
      transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transplantation is the therapy of choice for most patients with stage 5 chronic kidney&#xD;
      disease (CKD) and end stage renal disease (ESRD). Kidney transplantation improves quality of&#xD;
      life and overall survival rates. Cardiovascular disease is the most common complication and&#xD;
      leading cause of death in the transplant population. In order to assess the risk of cardiac&#xD;
      events perioperatively and after kidney transplantation, the majority of kidney&#xD;
      transplantation candidates undergo cardiac evaluation, including non-invasive cardiac stress&#xD;
      imaging or invasive coronary angiography before transplantation. Invasive coronary&#xD;
      angiography is associated with small but definite risk of bleeding or myocardial infarction,&#xD;
      making non-invasive cardiac stress imaging such as dobutamine stress echocardiography (DSE)&#xD;
      or nuclear myocardial perfusion scintigraphy (MPS) the preferred method. However,&#xD;
      non-invasive cardiac stress imaging in patients with stage 5 CKD and ESRD demonstrates only&#xD;
      moderate accuracy. DSE and MPS showed only sensitivities ranging from 0.44 to 0.89 and from&#xD;
      0.29 to 0.92, respectively, for identifying one or more severe coronary artery stenosis&#xD;
      (defined as coronary diameter stenosis of more than 70%). Due to the moderate accuracy,&#xD;
      several transplant centers (including Stanford) still continue to rely on invasive coronary&#xD;
      angiography for their populations instead of non-invasive cardiac testing. Thus improved&#xD;
      non-invasive cardiac testing with higher sensitivities and specificity are highly desirable&#xD;
      in this patient population.&#xD;
&#xD;
      A promising alternative is the use of coronary CT angiography (cCTA) in combination with CT&#xD;
      based fractional flow reserve (CT-FFR). Non-invasive cCTA alone has recently been evaluated&#xD;
      in kidney transplantation candidates. It demonstrated high sensitivity (0.93) but limited&#xD;
      specificity (0.63) in the detection of obstructive coronary artery disease, most likely&#xD;
      related to the high prevalence of coronary artery calcifications in patients with CKD and&#xD;
      ESRD. The specificity of coronary CTA can be improved by a new image analysis techniques,&#xD;
      which allow the calculation of the hemodynamic significance - expressed as the relative&#xD;
      pressure drop across a lesion similar - based on computational fluid dynamics derived from&#xD;
      the conventional coronary CTA (6). In various study populations, the combination of coronary&#xD;
      CT angiography and CT FFR showed excellent correlation with invasive FFR derived from&#xD;
      invasive coronary angiography, which is the current gold standard. The implementation of CT-&#xD;
      FFR has shown an improvement of the specificity of coronary CTA , even in the presence of&#xD;
      coronary artery calcifications. However, no study so far assessed the diagnostic accuracy of&#xD;
      coronary angiography with CT-FFR in candidates for kidney transplantation.&#xD;
&#xD;
      Goal The objective of this project is to evaluate and establish a new non-invasive cardiac&#xD;
      test in the detection of coronary artery disease for candidates before kidney&#xD;
      transplantation.&#xD;
&#xD;
      Specific Aims We want to confirm the promising results of CT FFR in this specific patient&#xD;
      population and want to establish an alternative non-invasive cardiac test.&#xD;
&#xD;
      Study Design This study is designed as a prospective observational cohort study with a study&#xD;
      population of 50 -100 patients. All patients who are included in this study will undergo&#xD;
      coronary CT angiography with CT-FFR (research part) and a clinically indicated invasive&#xD;
      coronary angiography with invasive FFR (standard of care). Coronary angiography and invasive&#xD;
      FFR will act as the reference standard.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Difficulty with recruitment in this patient population.&#xD;
  </why_stopped>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Actual">January 24, 2020</completion_date>
  <primary_completion_date type="Actual">January 24, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnostic accuracy of CT FFR.</measure>
    <time_frame>CT FFR and Invasive FFR are calculated immediately after coronary CT angiography and invasive coronary angiography</time_frame>
    <description>Diagnostic accuracy of CT FFR (per vessel) in the detection of hemodynamically significant CAD as compared to invasive FFR derived from invasive coronary angiography (reference standard). Presence or absence of hemodynamically significant coronary artery disease in concordance between CT FFR and invasive FFR. Hemodynamically significant stenosis is defined as CT FFR value below 0.8.</description>
  </primary_outcome>
  <enrollment type="Actual">26</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Computed Tomography</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CT FFR</intervention_name>
    <description>CT FFR calculated the fractional flow reserve based on the data derived for a regular coronary CT angiography. Computation is based on development of an anatomic model of the epicardial coronary arteries for each case and calculating the maximum coronary flow during maximal hyperaemia based on a mathematical model incorporating fluid dynamics. These post-processing steps require quantification of the patient-specific myocardial mass as this allows for an estimation of the baseline coronary blood flow.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Candidates for kidney transplantation without any residual kidney function and referred to&#xD;
        cardiac evaulation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Candidates for kidney transplantation on dialysis without any residual kidney function&#xD;
             AND referred to invasive coronary angiography for cardiac evaluation&#xD;
&#xD;
          -  Referral to invasive coronary angiography is based on algorithm used at the Transplant&#xD;
             Readiness Assessment Clinic (TRAC) at Stanford:&#xD;
&#xD;
          -  A. Diabetic Candidates older than 45 years.&#xD;
&#xD;
          -  B. Diabetic Candidates under 45 years old and any one of the following criteria is&#xD;
             present:&#xD;
&#xD;
          -  a) 25 year History of Diabetes&#xD;
&#xD;
          -  b) 5 year Smoking History&#xD;
&#xD;
          -  c) Abnormal EKG (ST-T wave changes)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hemodynamically and clinically unstable condition (angina at rest, malignant&#xD;
             arrhythmias)&#xD;
&#xD;
          -  Known ischemic heart disease (prior, documented myocardial infarction, prior stenting&#xD;
             or coronary artery bypass graft surgery)&#xD;
&#xD;
          -  BMI&gt;30 kg/m2, or weight &gt;120 kg.&#xD;
&#xD;
          -  Atrial fibrillation or other arrhythmia, &gt;6 ectopic beats per minute&#xD;
&#xD;
          -  Known or suspected allergy to iodinated contrast medium&#xD;
&#xD;
          -  Pregnancy cannot be excluded&#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>Dominik Fleischmann, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford Radiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford Healthcare</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>December 16, 2021</last_update_submitted>
  <last_update_submitted_qc>December 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Dominik Fleischmann, MD</investigator_full_name>
    <investigator_title>Professor of Radiology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</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/NCT03248674
org study id: IRB-41455
nct id: NCT03248674
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
Patients with chronic kidney disease (CKD) before kidney transplantation require that
      obstructive coronary artery disease (CAD) is excluded, as cardiovascular complications are
      the leading cause of mortality in kidney transplant patients. However, in this patient
      population, the optimal method for the detection of obstructive CAD has not been identified.
      Noninvasive stress tests such as Dobutamine stress echocardiography or nuclear perfusion
      study have low diagnostic accuracy. CT fractional flow reserve measurement (CT FFR) is a
      novel non-invasive (FDA approved) imaging test to identify obstructive CAD. The goal of this
      project is to evaluate the diagnostic accuracy of CT FFR in the detection of obstructive
      coronary artery disease in patients with chronic kidney disease before kidney
      transplantation.
Transplantation is the therapy of choice for most patients with stage 5 chronic kidney
      disease (CKD) and end stage renal disease (ESRD). Kidney transplantation improves quality of
      life and overall survival rates. Cardiovascular disease is the most common complication and
      leading cause of death in the transplant population. In order to assess the risk of cardiac
      events perioperatively and after kidney transplantation, the majority of kidney
      transplantation candidates undergo cardiac evaluation, including non-invasive cardiac stress
      imaging or invasive coronary angiography before transplantation. Invasive coronary
      angiography is associated with small but definite risk of bleeding or myocardial infarction,
      making non-invasive cardiac stress imaging such as dobutamine stress echocardiography (DSE)
      or nuclear myocardial perfusion scintigraphy (MPS) the preferred method. However,
      non-invasive cardiac stress imaging in patients with stage 5 CKD and ESRD demonstrates only
      moderate accuracy. DSE and MPS showed only sensitivities ranging from 0.44 to 0.89 and from
      0.29 to 0.92, respectively, for identifying one or more severe coronary artery stenosis
      (defined as coronary diameter stenosis of more than 70%). Due to the moderate accuracy,
      several transplant centers (including Stanford) still continue to rely on invasive coronary
      angiography for their populations instead of non-invasive cardiac testing. Thus improved
      non-invasive cardiac testing with higher sensitivities and specificity are highly desirable
      in this patient population.

      A promising alternative is the use of coronary CT angiography (cCTA) in combination with CT
      based fractional flow reserve (CT-FFR). Non-invasive cCTA alone has recently been evaluated
      in kidney transplantation candidates. It demonstrated high sensitivity (0.93) but limited
      specificity (0.63) in the detection of obstructive coronary artery disease, most likely
      related to the high prevalence of coronary artery calcifications in patients with CKD and
      ESRD. The specificity of coronary CTA can be improved by a new image analysis techniques,
      which allow the calculation of the hemodynamic significance - expressed as the relative
      pressure drop across a lesion similar - based on computational fluid dynamics derived from
      the conventional coronary CTA (6). In various study populations, the combination of coronary
      CT angiography and CT FFR showed excellent correlation with invasive FFR derived from
      invasive coronary angiography, which is the current gold standard. The implementation of CT-
      FFR has shown an improvement of the specificity of coronary CTA , even in the presence of
      coronary artery calcifications. However, no study so far assessed the diagnostic accuracy of
      coronary angiography with CT-FFR in candidates for kidney transplantation.

      Goal The objective of this project is to evaluate and establish a new non-invasive cardiac
      test in the detection of coronary artery disease for candidates before kidney
      transplantation.

      Specific Aims We want to confirm the promising results of CT FFR in this specific patient
      population and want to establish an alternative non-invasive cardiac test.

      Study Design This study is designed as a prospective observational cohort study with a study
      population of 50 -100 patients. All patients who are included in this study will undergo
      coronary CT angiography with CT-FFR (research part) and a clinically indicated invasive
      coronary angiography with invasive FFR (standard of care). Coronary angiography and invasive
      FFR will act as the reference standard.
observational model: Cohort
time perspective: Prospective
measure: Diagnostic accuracy of CT FFR.
time frame: CT FFR and Invasive FFR are calculated immediately after coronary CT angiography and invasive coronary angiography
description: Diagnostic accuracy of CT FFR (per vessel) in the detection of hemodynamically significant CAD as compared to invasive FFR derived from invasive coronary angiography (reference standard). Presence or absence of hemodynamically significant coronary artery disease in concordance between CT FFR and invasive FFR. Hemodynamically significant stenosis is defined as CT FFR value below 0.8.
intervention type: Diagnostic Test
intervention name: CT FFR
description: CT FFR calculated the fractional flow reserve based on the data derived for a regular coronary CT angiography. Computation is based on development of an anatomic model of the epicardial coronary arteries for each case and calculating the maximum coronary flow during maximal hyperaemia based on a mathematical model incorporating fluid dynamics. These post-processing steps require quantification of the patient-specific myocardial mass as this allows for an estimation of the baseline coronary blood flow.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Dominik Fleischmann, M.D.
role: Principal Investigator
affiliation: Stanford Radiology
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Dominik Fleischmann, MD
investigator title: Professor of Radiology
mesh term: Coronary Artery Disease
sharing ipd: No