<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/NCT02208765</url>
  </required_header>
  <id_info>
    <org_study_id>38RC13.723</org_study_id>
    <nct_id>NCT02208765</nct_id>
  </id_info>
  <brief_title>Prognostic Value of SPECT-imaging Myocardial Perfusion Heterogeneity</brief_title>
  <acronym>EVAPERF</acronym>
  <official_title>Prognostic Value of Myocardial Perfusion Heterogeneity Assessed by Stress Single Photon Emission Computed Tomography</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Grenoble</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Endothelial dysfunction has been demonstrated to be an early marker of coronary artery&#xD;
      disease (CAD). On the other hand, myocardial perfusion single photon emission computed&#xD;
      tomography (MP-SPECT) is a widely used technique for evaluation of patients with suspected or&#xD;
      known CAD.&#xD;
&#xD;
      Preliminary data suggest that myocardial perfusion heterogeneity (a potential surrogate&#xD;
      marker of endothelial dysfunction) can be assessed on conventional MP-SPECT, but its additive&#xD;
      and independent prognostic value over the presence of myocardial ischemia remain unknown.&#xD;
&#xD;
      More over, factual data demonstrate that inhalation of particulate matters and gaz (NO2, CO)&#xD;
      from air pollution contributes to the development of cardiovascular diseases in the short and&#xD;
      long term. The role of air pollution in endothelial dysfunction has been suggested.&#xD;
&#xD;
      Accordingly, the purpose of this study is to evaluate the prognostic value of myocardial&#xD;
      perfusion heterogeneity assessed by a new automatized image processing method applied to&#xD;
      routine MP-SPECT.&#xD;
&#xD;
      The second purpose is to evaluate the role of air pollution exposure in pathogenesis of&#xD;
      cardiovascular disease.&#xD;
&#xD;
      The main hypothesis is that the presence of myocardial perfusion heterogeneity is predictive&#xD;
      of 2-year cardiovascular events in patients referred to the Nuclear Cardiology Department for&#xD;
      routine evaluation of known or suspected CAD.&#xD;
&#xD;
      The second hypothesis is that microcirculatory coronary dysfunction is a causal link between&#xD;
      air pollution and cardiovascular disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. SPECT imaging protocol and analysis Stress tests and SPECTs are performed according to&#xD;
           the routine protocols in use in our center. Briefly, at peak stress, patients were&#xD;
           injected with thallium-201. Five to 10 minutes after stress, a 5-minutes supine&#xD;
           acquisition was performed followed by a 5-minutes prone acquisition. Subsequently,&#xD;
           technetium-99m-sestamibi was injected, and 2 minutes later a single 5-minutes rest&#xD;
           acquisition was performed. During stress acquisition, patients were imaged in supine and&#xD;
           prone positions with their arms positioned over their head. The rest acquisition was&#xD;
           only acquired in supine position. The gated SPECT studies were performed at each&#xD;
           acquisition. Injected activity (IA) was adjusted for patient weight. For weights of &lt;80&#xD;
           kg/ 80-100 kg/&gt;100 kg, thallium-201 IAs were 74/92/111 MBq and technetium-99m-sestamibi&#xD;
           IAs were 300/370/450 MBq, respectively. A uniform imaging pre-treatment for the&#xD;
           reconstruction of raw myocardial perfusion imaging data was applied, and images were&#xD;
           reconstructed and reoriented to obtain transaxial sections of the left ventricle&#xD;
           according to the three standard cardiac planes.&#xD;
&#xD;
        2. In this study, we use a new mathematic technique from entropy analysis to provide&#xD;
           precise, objective, automated quantification of perfusion heterogeneity at stress with&#xD;
           camera SPECT. This method may be a non-invasive imaging to assess coronary microvascular&#xD;
           dysfunction.&#xD;
&#xD;
        3. Air pollution exposure (particule matters and gaz) is estimated by SIRANE dispersion&#xD;
           models validated by Air Rhône-Alpes, our regional agency tasked with protecting and&#xD;
           managing the ambient air quality. The dispersion models are used to estimate the&#xD;
           downwind ambient concentration of air pollutants or toxins emitted from sources such as&#xD;
           industrial plants, vehicular traffic or accidental chemical releases.&#xD;
&#xD;
      Air pollution is estimated for each patient thanks to their postal private and professional&#xD;
      adresses for different windows of exposure :&#xD;
&#xD;
        -  short term windows (2hours to 7 days before the MP-SPECT and cardiovascular events).&#xD;
&#xD;
        -  long term windows (1 - 5 years before the MP-SPECT and before cardiovascular events)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</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>Major Adverse Cardiac and Cerebrovascular Events (MACCEs)</measure>
    <time_frame>2 years</time_frame>
    <description>Composite outcome : cardiac death and/or acute coronary syndrome and/or coronary artery bypass graft and/or percutaneous coronary intervention and/or stroke and/or symptomatic peripheral artery disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of cardiac death or nonfatal Myocardial Infarction</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of cardiac death or nonfatal Myocardial Infarction or stroke</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of participants with myocardial revascularization</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of all death or non fatal Myocardial Infarction</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of all death or non fatal Myocardial Infarction or non fatal stroke</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of all death or non fatal Myocardial Infarction or non fatal stroke or number of participants with myocardial revascularization</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite secondary outcome : number of all death or non fatal Myocardial Infarction or non fatal stroke or number of participants with myocardial revascularization or symptomatic peripheral artery disease</measure>
    <time_frame>2 years</time_frame>
    <description>peripheral artery disease (intermittent claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cardiac death</measure>
    <time_frame>2 years</time_frame>
    <description>Death from coronary artery disease, heart failure, or sudden death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non fatal Myocardial Infarction</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>acute coronary syndrome</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non fatal Stroke</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coronary artery bypass graft and/or percutaneous coronary intervention</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>14 Symptomatic peripheral artery disease (intermittent claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>influence of air pollution exposure for short and long terms of exposure on myocardial Heterogeneity Index</measure>
    <time_frame>inclusion</time_frame>
    <description>Air pollution is estimated for each patient thanks to their postal private and professional adresses for different windows of exposure :&#xD;
short term windows (2hours to 7 days before the MP-SPECT and cardiovascular events).&#xD;
long term windows (1 - 5 years before the MP-SPECT and before cardiovascular events)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>influence of air pollution exposure for short and long terms of exposure on cardiovascular events</measure>
    <time_frame>2 years</time_frame>
    <description>Air pollution is estimated for each patient thanks to their postal private and professional adresses for different windows of exposure :&#xD;
short term windows (2hours to 7 days before the MP-SPECT and cardiovascular events).&#xD;
long term windows (1 - 5 years before the MP-SPECT and before cardiovascular events)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1600</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Coronary Atherosclerosis</condition>
  <arm_group>
    <arm_group_label>Study cohort</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Any patient referred to the Nuclear Cardiology Laboratory of the University Hospital of Grenoble for myocardial perfusion imaging for diagnosis or prognosis evaluation of suspected or know coronary artery disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Stress Single Photon Emission Computed Tomography</intervention_name>
    <arm_group_label>Study cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Clinical indication for myocardial perfusion imaging&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast feeding women&#xD;
&#xD;
          -  Severe comorbidity with life expectancy 6 months&#xD;
&#xD;
          -  Left bundle branch block on ECG making heteogeneity analysis impossible&#xD;
&#xD;
          -  Patient not resident in the Rhône-Alpes region&#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>Gerald Vanzetto, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Grenoble</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Grenoble</city>
        <zip>38000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation. 2003 Oct 28;108(17):2054-9. doi: 10.1161/01.CIR.0000089191.72957.ED. No abstract available.</citation>
    <PMID>14581384</PMID>
  </reference>
  <reference>
    <citation>Schindler TH, Nitzsche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, Brink I, Zhang XL, Kreissl M, Magosaki N, Just H, Solzbach U. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol. 2005 May 3;45(9):1505-12. doi: 10.1016/j.jacc.2005.01.040.</citation>
    <PMID>15862426</PMID>
  </reference>
  <reference>
    <citation>Vanzetto G, Ormezzano O, Fagret D, Comet M, Denis B, Machecourt J. Long-term additive prognostic value of thallium-201 myocardial perfusion imaging over clinical and exercise stress test in low to intermediate risk patients : study in 1137 patients with 6-year follow-up. Circulation. 1999 Oct 5;100(14):1521-7. doi: 10.1161/01.cir.100.14.1521.</citation>
    <PMID>10510055</PMID>
  </reference>
  <reference>
    <citation>Johnson NP, Gould KL. Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. J Nucl Med. 2005 Sep;46(9):1427-37.</citation>
    <PMID>16157524</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>May 18, 2022</last_update_submitted>
  <last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Coronary Circulation</keyword>
  <keyword>Coronary Artery Disease</keyword>
  <keyword>Myocardial perfusion imaging</keyword>
  <keyword>Prognosis</keyword>
  <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>
    <mesh_term>Atherosclerosis</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/NCT02208765
org study id: 38RC13.723
nct id: NCT02208765
lead sponsor: 
has dmc: Yes
Endothelial dysfunction has been demonstrated to be an early marker of coronary artery
      disease (CAD). On the other hand, myocardial perfusion single photon emission computed
      tomography (MP-SPECT) is a widely used technique for evaluation of patients with suspected or
      known CAD.

      Preliminary data suggest that myocardial perfusion heterogeneity (a potential surrogate
      marker of endothelial dysfunction) can be assessed on conventional MP-SPECT, but its additive
      and independent prognostic value over the presence of myocardial ischemia remain unknown.

      More over, factual data demonstrate that inhalation of particulate matters and gaz (NO2, CO)
      from air pollution contributes to the development of cardiovascular diseases in the short and
      long term. The role of air pollution in endothelial dysfunction has been suggested.

      Accordingly, the purpose of this study is to evaluate the prognostic value of myocardial
      perfusion heterogeneity assessed by a new automatized image processing method applied to
      routine MP-SPECT.

      The second purpose is to evaluate the role of air pollution exposure in pathogenesis of
      cardiovascular disease.

      The main hypothesis is that the presence of myocardial perfusion heterogeneity is predictive
      of 2-year cardiovascular events in patients referred to the Nuclear Cardiology Department for
      routine evaluation of known or suspected CAD.

      The second hypothesis is that microcirculatory coronary dysfunction is a causal link between
      air pollution and cardiovascular disease.
1. SPECT imaging protocol and analysis Stress tests and SPECTs are performed according to
           the routine protocols in use in our center. Briefly, at peak stress, patients were
           injected with thallium-201. Five to 10 minutes after stress, a 5-minutes supine
           acquisition was performed followed by a 5-minutes prone acquisition. Subsequently,
           technetium-99m-sestamibi was injected, and 2 minutes later a single 5-minutes rest
           acquisition was performed. During stress acquisition, patients were imaged in supine and
           prone positions with their arms positioned over their head. The rest acquisition was
           only acquired in supine position. The gated SPECT studies were performed at each
           acquisition. Injected activity (IA) was adjusted for patient weight. For weights of <80
           kg/ 80-100 kg/>100 kg, thallium-201 IAs were 74/92/111 MBq and technetium-99m-sestamibi
           IAs were 300/370/450 MBq, respectively. A uniform imaging pre-treatment for the
           reconstruction of raw myocardial perfusion imaging data was applied, and images were
           reconstructed and reoriented to obtain transaxial sections of the left ventricle
           according to the three standard cardiac planes.

        2. In this study, we use a new mathematic technique from entropy analysis to provide
           precise, objective, automated quantification of perfusion heterogeneity at stress with
           camera SPECT. This method may be a non-invasive imaging to assess coronary microvascular
           dysfunction.

        3. Air pollution exposure (particule matters and gaz) is estimated by SIRANE dispersion
           models validated by Air Rhône-Alpes, our regional agency tasked with protecting and
           managing the ambient air quality. The dispersion models are used to estimate the
           downwind ambient concentration of air pollutants or toxins emitted from sources such as
           industrial plants, vehicular traffic or accidental chemical releases.

      Air pollution is estimated for each patient thanks to their postal private and professional
      adresses for different windows of exposure :

        -  short term windows (2hours to 7 days before the MP-SPECT and cardiovascular events).

        -  long term windows (1 - 5 years before the MP-SPECT and before cardiovascular events)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Major Adverse Cardiac and Cerebrovascular Events (MACCEs)
time frame: 2 years
description: Composite outcome : cardiac death and/or acute coronary syndrome and/or coronary artery bypass graft and/or percutaneous coronary intervention and/or stroke and/or symptomatic peripheral artery disease
measure: composite secondary outcome : number of cardiac death or nonfatal Myocardial Infarction
time frame: 2 years
measure: composite secondary outcome : number of cardiac death or nonfatal Myocardial Infarction or stroke
time frame: 2 years
measure: composite secondary outcome : number of participants with myocardial revascularization
time frame: 2 years
measure: composite secondary outcome : number of all death or non fatal Myocardial Infarction
time frame: 2 years
measure: composite secondary outcome : number of all death or non fatal Myocardial Infarction or non fatal stroke
time frame: 2 years
measure: composite secondary outcome : number of all death or non fatal Myocardial Infarction or non fatal stroke or number of participants with myocardial revascularization
time frame: 2 years
measure: composite secondary outcome : number of all death or non fatal Myocardial Infarction or non fatal stroke or number of participants with myocardial revascularization or symptomatic peripheral artery disease
time frame: 2 years
description: peripheral artery disease (intermittent claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation).
measure: cardiac death
time frame: 2 years
description: Death from coronary artery disease, heart failure, or sudden death
measure: Non fatal Myocardial Infarction
time frame: 2 years
measure: acute coronary syndrome
time frame: 2 years
measure: Non fatal Stroke
time frame: 2 years
measure: Coronary artery bypass graft and/or percutaneous coronary intervention
time frame: 2 years
measure: 14 Symptomatic peripheral artery disease (intermittent claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation)
time frame: 2 years
measure: influence of air pollution exposure for short and long terms of exposure on myocardial Heterogeneity Index
time frame: inclusion
description: Air pollution is estimated for each patient thanks to their postal private and professional adresses for different windows of exposure :
short term windows (2hours to 7 days before the MP-SPECT and cardiovascular events).
long term windows (1 - 5 years before the MP-SPECT and before cardiovascular events)
measure: influence of air pollution exposure for short and long terms of exposure on cardiovascular events
time frame: 2 years
description: Air pollution is estimated for each patient thanks to their postal private and professional adresses for different windows of exposure :
short term windows (2hours to 7 days before the MP-SPECT and cardiovascular events).
long term windows (1 - 5 years before the MP-SPECT and before cardiovascular events)
arm group label: Study cohort
arm group type: Other
description: Any patient referred to the Nuclear Cardiology Laboratory of the University Hospital of Grenoble for myocardial perfusion imaging for diagnosis or prognosis evaluation of suspected or know coronary artery disease
intervention type: Device
intervention name: Stress Single Photon Emission Computed Tomography
arm group label: Study cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gerald Vanzetto, MD, PhD
role: Principal Investigator
affiliation: University Hospital, Grenoble
facility: 
country: France
citation: Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation. 2003 Oct 28;108(17):2054-9. doi: 10.1161/01.CIR.0000089191.72957.ED. No abstract available.
PMID: 14581384
citation: Schindler TH, Nitzsche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, Brink I, Zhang XL, Kreissl M, Magosaki N, Just H, Solzbach U. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol. 2005 May 3;45(9):1505-12. doi: 10.1016/j.jacc.2005.01.040.
PMID: 15862426
citation: Vanzetto G, Ormezzano O, Fagret D, Comet M, Denis B, Machecourt J. Long-term additive prognostic value of thallium-201 myocardial perfusion imaging over clinical and exercise stress test in low to intermediate risk patients : study in 1137 patients with 6-year follow-up. Circulation. 1999 Oct 5;100(14):1521-7. doi: 10.1161/01.cir.100.14.1521.
PMID: 10510055
citation: Johnson NP, Gould KL. Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. J Nucl Med. 2005 Sep;46(9):1427-37.
PMID: 16157524
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Atherosclerosis