<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/NCT04448691</url>
  </required_header>
  <id_info>
    <org_study_id>23534</org_study_id>
    <nct_id>NCT04448691</nct_id>
  </id_info>
  <brief_title>&quot;SIMULATION MODELING OF CORONARY ARTERY DISEASE: A TOOL FOR CLINICAL DECISION SUPPORT&quot;</brief_title>
  <acronym>SMARTool</acronym>
  <official_title>&quot;SIMULATION MODELING OF CORONARY ARTERY DISEASE: A TOOL FOR CLINICAL DECISION SUPPORT&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione C.N.R./Regione Toscana &quot;G. Monasterio&quot;, Pisa, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Turku University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Azienda USL 12 Versilia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Federico II University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Catala de Salut</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Cardiology, Warsaw, Poland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fondazione C.N.R./Regione Toscana &quot;G. Monasterio&quot;, Pisa, Italy</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Coronary atherosclerosis (ATS) is a degenerative-inflammatory artery pathology underlying the&#xD;
      different clinical manifestations of coronary heart disease (CHD), from stable angina due to&#xD;
      constrictive plaque growth obstructing artery lumen, to acute coronary syndrome (ACS),&#xD;
      secondary to abrupt lumen occlusion by atherothrombosis at the site of a ruptured or eroded&#xD;
      plaque.&#xD;
&#xD;
      Major coronary adverse events (MACE) are known to be related to local factors, the so called&#xD;
      &quot;high risk plaque&quot; characterized by large lipid-necrotic core with a thin fibrous cap,&#xD;
      intraplaque hemorrhage, rupture, erosion, and to systemic, patient-specific, factors,&#xD;
      contributing to the atherogenic genotype/phenotype of the so called &quot;high risk patient&quot;,&#xD;
      presenting with an abnormally activated thrombogenic and/or inflammatory state or increased&#xD;
      plasma levels of atherogenic lipid species.&#xD;
&#xD;
      The huge social and economic impact of CHD in western and developing countries is primarily&#xD;
      due to the difficulty to identify and predict, in the clinical context, which &quot;high risk&#xD;
      plaque&quot; in which &quot;high risk patient&quot; will cause, independently of stenosis severity, an acute&#xD;
      coronary event such as myocardial infarction or sudden coronary death, which are often the&#xD;
      first manifestations of CHD in a large proportion of otherwise asymptomatic subjects. Plaque&#xD;
      burden, compared to stenosis, is recognized as a better predictor of ACS and coronary CT&#xD;
      angiography (CCTA) is considered as the optimal non-invasive coronary imaging modality to&#xD;
      assess and quantify plaque burden and to evaluate the functional significance of a stenosis,&#xD;
      by computationally estimating fractional flow reserve. Moreover, molecular studies of CHD&#xD;
      patients have mostly examined associations with clinical cardiovascular outcomes:&#xD;
      associations with coronary ATS assessed by quantitative CCTA may provide insight into the&#xD;
      pathophysiological role of several molecular species in plaque formation and growth, and&#xD;
      elucidate their potential role as discriminative biomarkers of CHD.&#xD;
&#xD;
      Based on these considerations, aim of this study is to collect and analyze all&#xD;
      patient-specific clinical and epidemiological data and patient phenotype and genotype&#xD;
      blood-derived molecular information, and to combine them with local high resolution&#xD;
      non-invasive CCTA imaging of actual plaque burden as well as, prospectively, of its increase&#xD;
      or de novo formation over a clinically relevant timespan. The expected result, following&#xD;
      local and systemic data integration and modeling, is to optimize early diagnosis and risk&#xD;
      stratification of CHD beyond current clinical models and scores and to help improving primary&#xD;
      and secondary prevention of MACE. The overall design of this diagnostic and prognostic&#xD;
      framework has been proposed to Horizon 2020 EU Call PHC30 and approved by the European&#xD;
      Commission (Grant Agreement PHC30-689068). The Consortium includes major clinical European&#xD;
      University Hospitals specialized in CHD imaging and treatment and the project study has&#xD;
      obtained the endorsement of the European Society of Cardiovascular Imaging.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 14, 2016</start_date>
  <completion_date type="Actual">December 30, 2017</completion_date>
  <primary_completion_date type="Actual">October 30, 2017</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>
    <intervention_model_description>prospective study with serial CCTA</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>coronary artery disease progression assessed by CCTA</measure>
    <time_frame>6 years CCTA follow up</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">275</enrollment>
  <condition>Management/Treatment of Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>CCTA</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Suspected coronary disease patients enrolled in EVINCI trial with CCTA where recalled for follow up CCTA and blood sampling</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CCTA</intervention_name>
    <description>requested follow up CCTA</description>
    <arm_group_label>CCTA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. male and female subjects&#xD;
&#xD;
          2. aged 45-75 years&#xD;
&#xD;
          3. caucasian population&#xD;
&#xD;
          4. submitted to CCTA for suspected CHD between 2009 and 2012 (in the context of EVINCI&#xD;
             and ARTreat FPVII studies) at the Hospitals reported in &quot;SMARTool Clinical Center&quot;&#xD;
             document and satisfying the elegibility criteria reported above&#xD;
&#xD;
          5. submitted to clinical Follow-up in the last 6 months with stable clinical conditions&#xD;
             and documented CHD or persistent intermediate/high probability of CHD&#xD;
&#xD;
          6. Signed informed consents (clinical and genetic)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Multi-vessel severe disease (3 vessels and/or LM disease with &gt;90% stenosis).&#xD;
&#xD;
          2. Severe coronary calcification (CAC score &gt; 600).&#xD;
&#xD;
          3. Having undergone surgical procedures related to heart diseases (CABG, valve&#xD;
             replacement, CRT or CRTD treatment, any surgery of the heart or arteries).&#xD;
&#xD;
          4. Documented MACE at history (myocardial infarction, severe heart failure, recurrent&#xD;
             angina) in the last 6 months with/without revascularization&#xD;
&#xD;
          5. Documented severe peripheral vascular disease (carotid, femoral)&#xD;
&#xD;
          6. Surgery of carotid and/or peripheral arteries or cerebral ischemic attack&#xD;
&#xD;
          7. History/surgery of Abdominal Aortic Aneurysm(AAA).&#xD;
&#xD;
          8. Severe Heart failure (NYHA Class III-IV)&#xD;
&#xD;
          9. LV dysfunction (left ventricle EF &lt;40%).&#xD;
&#xD;
         10. Atrial fibrillation.&#xD;
&#xD;
         11. Lack of written informed consent (clinical consent and/or genetic consent)&#xD;
&#xD;
         12. Pregnancy (evaluated by urine test) and breastfeeding&#xD;
&#xD;
         13. Active Cancer&#xD;
&#xD;
         14. Asthma&#xD;
&#xD;
         15. Severe untreated Hypertension (arterial blood pressure ≥ 170/110 mmHg)&#xD;
&#xD;
         16. Cardiomyopathy or congenital heart disease&#xD;
&#xD;
         17. Significant valvular disease (hemodynamically significant valvular stenosis or&#xD;
             insufficiency by echoDoppler)&#xD;
&#xD;
         18. Renal dysfunction (creatinine &gt; 1.3 mg/dL)&#xD;
&#xD;
         19. Chronic Kidney Disease (eGFR &lt; 30 ml/min/1.73 m2)&#xD;
&#xD;
         20. Hepatic failure (at least 3 of the following: albumin &lt; 3.5 g/dL; prolonged&#xD;
             prothrombin time-PT; jaundice; ascites)&#xD;
&#xD;
         21. Waldenstrom disease&#xD;
&#xD;
         22. Multiple myeloma&#xD;
&#xD;
         23. Autoimmune/Acute inflammatory disease&#xD;
&#xD;
         24. Previous severe adverse reaction to iodine contrast agent&#xD;
&#xD;
         25. Positivity at blood tests for HIV, Hepatitis B and C (CRF number 1-clinical&#xD;
             evaluation)&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://www.smartool.eu</url>
    <description>H2020 project website</description>
  </link>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione C.N.R./Regione Toscana &quot;G. Monasterio&quot;, Pisa, Italy</investigator_affiliation>
    <investigator_full_name>Silvia Rocchiccioli</investigator_full_name>
    <investigator_title>Project Coordinator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary 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/NCT04448691
org study id: 23534
nct id: NCT04448691
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Coronary atherosclerosis (ATS) is a degenerative-inflammatory artery pathology underlying the
      different clinical manifestations of coronary heart disease (CHD), from stable angina due to
      constrictive plaque growth obstructing artery lumen, to acute coronary syndrome (ACS),
      secondary to abrupt lumen occlusion by atherothrombosis at the site of a ruptured or eroded
      plaque.

      Major coronary adverse events (MACE) are known to be related to local factors, the so called
      "high risk plaque" characterized by large lipid-necrotic core with a thin fibrous cap,
      intraplaque hemorrhage, rupture, erosion, and to systemic, patient-specific, factors,
      contributing to the atherogenic genotype/phenotype of the so called "high risk patient",
      presenting with an abnormally activated thrombogenic and/or inflammatory state or increased
      plasma levels of atherogenic lipid species.

      The huge social and economic impact of CHD in western and developing countries is primarily
      due to the difficulty to identify and predict, in the clinical context, which "high risk
      plaque" in which "high risk patient" will cause, independently of stenosis severity, an acute
      coronary event such as myocardial infarction or sudden coronary death, which are often the
      first manifestations of CHD in a large proportion of otherwise asymptomatic subjects. Plaque
      burden, compared to stenosis, is recognized as a better predictor of ACS and coronary CT
      angiography (CCTA) is considered as the optimal non-invasive coronary imaging modality to
      assess and quantify plaque burden and to evaluate the functional significance of a stenosis,
      by computationally estimating fractional flow reserve. Moreover, molecular studies of CHD
      patients have mostly examined associations with clinical cardiovascular outcomes:
      associations with coronary ATS assessed by quantitative CCTA may provide insight into the
      pathophysiological role of several molecular species in plaque formation and growth, and
      elucidate their potential role as discriminative biomarkers of CHD.

      Based on these considerations, aim of this study is to collect and analyze all
      patient-specific clinical and epidemiological data and patient phenotype and genotype
      blood-derived molecular information, and to combine them with local high resolution
      non-invasive CCTA imaging of actual plaque burden as well as, prospectively, of its increase
      or de novo formation over a clinically relevant timespan. The expected result, following
      local and systemic data integration and modeling, is to optimize early diagnosis and risk
      stratification of CHD beyond current clinical models and scores and to help improving primary
      and secondary prevention of MACE. The overall design of this diagnostic and prognostic
      framework has been proposed to Horizon 2020 EU Call PHC30 and approved by the European
      Commission (Grant Agreement PHC30-689068). The Consortium includes major clinical European
      University Hospitals specialized in CHD imaging and treatment and the project study has
      obtained the endorsement of the European Society of Cardiovascular Imaging.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: prospective study with serial CCTA
primary purpose: Diagnostic
masking: None (Open Label)
measure: coronary artery disease progression assessed by CCTA
time frame: 6 years CCTA follow up
arm group label: CCTA
arm group type: Other
description: Suspected coronary disease patients enrolled in EVINCI trial with CCTA where recalled for follow up CCTA and blood sampling
intervention type: Diagnostic Test
intervention name: CCTA
description: requested follow up CCTA
arm group label: CCTA
criteria: 
gender: All
minimum age: 45 Years
maximum age: 75 Years
healthy volunteers: No
url: http://www.smartool.eu
description: H2020 project website
responsible party type: Principal Investigator
investigator affiliation: Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
investigator full name: Silvia Rocchiccioli
investigator title: Project Coordinator
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
sharing ipd: No