<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/NCT03252990</url>
  </required_header>
  <id_info>
    <org_study_id>NL58752.068.16</org_study_id>
    <nct_id>NCT03252990</nct_id>
  </id_info>
  <brief_title>18F-fluorocholine PET-MR Imaging of Coronary Plaque Vulnerability</brief_title>
  <official_title>Molecular Imaging of Coronary Plaque Vulnerability Using 18F-fluorocholine PET-MRI in Patients With Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>VieCuri Medical Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stichting de Weijerhorst</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</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>
      This study is designed as a prospective observational feasibility study. The investigators&#xD;
      will study whether vulnerable plaques on OCT (fibrous cap ≤ 70 μm) show a locally increased&#xD;
      uptake of 18F-choline on PET-MRI compared to stable plaques and whether the culprit plaque&#xD;
      shows a locally increased uptake of 18F-choline on PET-MRI compared to non-culprit plaques.&#xD;
      First, 15 NSTEMI or STEMI patients who underwent urgent percutaneous coronary intervention&#xD;
      (PCI) of the culprit vessel, who are diagnosed with multivessel coronary disease and are&#xD;
      currently scheduled for a second PCI at the VieCuri hospital will be included. These patients&#xD;
      will be subjected to an additional 18F-choline PET-MRI examination at the MUMC+ and an&#xD;
      additional optical coherence tomography (OCT) examination (during the PCI procedure at the&#xD;
      Viecuri hospital). OCT will be performed as a reference standard to validate 18F-choline&#xD;
      PET-MRI for detection of vulnerable plaques in the coronary arteries. In addition, 15 NSTEMI&#xD;
      patients, who are scheduled for PCI of the culprit lesion at the MUMC+, will be subjected to&#xD;
      an additional 18F-choline PET-MRI examination at the MUMC+. Hereby, the culprit coronary&#xD;
      vessel and thereby the culprit plaque can be identified by the location of the myocardial&#xD;
      infarct, as identified by late enhanced MRI. The investigators will study whether the culprit&#xD;
      plaque shows an increased 18F-choline uptake on 18F-choline PET-MRI compared to non-culprit&#xD;
      plaques in the other coronary arteries. All patients will receive standard, guideline-based&#xD;
      clinical care, while PET-MRI and OCT will be performed as additional measurements. Before the&#xD;
      start of the study, 5 stable angina pectoris patients that are scheduled for a PCI procedure&#xD;
      at the MUMC+ will be included at the MUMC+ for a single PET-MRI scan to optimize the&#xD;
      parameters of the coronary PET-MRI scan.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background of the study:&#xD;
&#xD;
      Myocardial infarction (MI) frequently recurs after MI, which may be related to insufficient&#xD;
      vulnerable plaque identification using invasive coronary angiography. More accurate&#xD;
      identification of vulnerable plaques may improve therapeutic strategies and clinical outcome.&#xD;
      Recently, the investigators demonstrated that 18F-choline PET can be used to identify&#xD;
      vulnerable carotid plaques. The investigators hypothesize that fully integrated 18F-choline&#xD;
      PET-MRI enables detection of vulnerable coronary plaques.&#xD;
&#xD;
      Objective of the study:&#xD;
&#xD;
      The objective is to study the feasibility to detect vulnerable coronary plaques with&#xD;
      18F-choline PET-MRI.&#xD;
&#xD;
      Primary study parameters/outcome of the study:&#xD;
&#xD;
        -  To investigate whether vulnerable plaques on OCT (fibrous cap ≤ 70 μm) show a locally&#xD;
           increased uptake of 18F-choline on PET-MRI compared to stable plaques.&#xD;
&#xD;
        -  To investigate whether the culprit plaque shows a locally increased uptake of&#xD;
           18F-choline on PET-MRI compared to non-culprit plaques.&#xD;
&#xD;
      Secondary study parameters/outcome of the study (if applicable):&#xD;
&#xD;
        -  To study whether there is a correlation between the uptake of 18F-choline in coronary&#xD;
           plaques and the degree of stenosis as shown on the angiogram acquired during the PCI&#xD;
           procedure&#xD;
&#xD;
        -  To study whether there is a correlation between the uptake of 18F-choline in coronary&#xD;
           plaques and the presence of macrophages, micro-calcifications, lipid-rich necrotic core&#xD;
           on OCT&#xD;
&#xD;
        -  To investigate whether there is an association between the uptake of 18F-choline in the&#xD;
           coronary arteries and that in the carotid arteries.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness (if applicable):&#xD;
&#xD;
      This study will not delay any necessary treatment and the study is not expected to adversely&#xD;
      affect outcome. The patients from the VieCuri will need to visit the MUMC for the additional&#xD;
      PET-MRI scan. All patients in this study, including the 5 patients for protocol optimisation,&#xD;
      will receive an average radiation dose of 5.3 mSv (0.019 mSv/MBq [see attachment 1], 280 MBq,&#xD;
      average body weight 70 kg) and a maximum radiation dose of 6.8 mSv (360 MBq, ≥ 90 kg body&#xD;
      weight) from the 18F-choline tracer. PET-MRI, Gadolinium and 18F-choline are safe and the&#xD;
      risk of adverse effects are low (as described in chapter 7). The additional OCT examination&#xD;
      is performed during the PCI procedure (only in the 15 patients of the VieCuri hospital), that&#xD;
      is part of standard patient care, and carries the same risks as the PCI procedure, including:&#xD;
      coronary dissection, air embolism, coronary thrombus, contrast nephropathy, contrast allergy,&#xD;
      cardiovascular event, and death (extremely rare). These risks will be minimized by the use of&#xD;
      heparin to achieve an Activating Clotting Time (ACT) value of 300, taking care of meticulous&#xD;
      positioning of the wire and using the OCT catheter under fluoroscopy guidance. Approximately&#xD;
      15% of the amount of contrast agent that is used during an PCI procedure will be additionally&#xD;
      administered during the OCT procedure and 30 seconds of additional fluoroscopy guidance with&#xD;
      associated increase in ionizing radiation dose will be used for positioning of the OCT&#xD;
      catheter. During the additional PET- MRI and OCT examinations, there is a chance on&#xD;
      accidental medical findings. These findings will be reported to the treating physician and&#xD;
      the general practitioner of the patient. Study results are expected to contribute to&#xD;
      improvement of vulnerable plaque detection for future patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2, 2018</start_date>
  <completion_date type="Actual">December 6, 2019</completion_date>
  <primary_completion_date type="Actual">December 6, 2019</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To investigate whether vulnerable plaques on OCT (fibrous cap ≤ 70 μm) show a locally increased uptake of 18F-choline on PET-MRI compared to stable plaques.</measure>
    <time_frame>72 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To investigate whether the culprit plaque shows a locally increased uptake of 18F-choline on PET-MRI compared to non-culprit plaques.</measure>
    <time_frame>72 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To study whether there is a correlation between the uptake of 18F-choline in coronary plaques and the degree of stenosis as shown on the angiogram acquired during the PCI procedure</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study whether there is a correlation between the uptake of 18F-choline in coronary plaques and the presence of macrophages, micro-calcifications, lipid-rich necrotic core on OCT</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To investigate whether there is an association between the uptake of 18F-choline in the coronary arteries and that in the carotid arteries.</measure>
    <time_frame>1.5 hours</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">15</enrollment>
  <condition>Myocardial Infarction</condition>
  <condition>Myocardial Ischemia</condition>
  <condition>Atherosclerosis</condition>
  <condition>Coronary Artery Disease</condition>
  <condition>Coronary Stenosis</condition>
  <condition>Heart Attack</condition>
  <condition>Multi Vessel Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Optimization subjects</arm_group_label>
    <description>Before the enrollment of the actual study subjects, 5 stable angina pectoris patients that are scheduled for a PCI procedure at the MUMC+ will be included at the MUMC+ for a single PET-MRI scan to optimize the parameters of the coronary PET-MRI scan. All patients will receive standard, guideline-based clinical care, while PET-MRI will be performed as an additional measurement.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients from the VieCuri hospital</arm_group_label>
    <description>15 NSTEMI or STEMI patients who underwent urgent percutaneous coronary intervention (PCI) of the culprit vessel, who are diagnosed with multivessel coronary disease and are currently scheduled for a second PCI at the VieCuri hospital will be included. These patients will be subjected to an additional 18F-choline PET-MRI examination at the MUMC+ and an additional optical coherence tomography (OCT) examination (during the PCI procedure) at the Viecuri hospital. OCT will be performed as a reference standard to validate 18F-choline PET-MRI for detection of vulnerable plaques in the coronary arteries. All patients will receive standard, guideline-based clinical care, while PET-MRI and OCT will be performed as additional measurements.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>PET-MRI</intervention_name>
    <description>Additional 18F-choline PET-MRI examination</description>
    <arm_group_label>Optimization subjects</arm_group_label>
    <arm_group_label>Patients from the VieCuri hospital</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Optical Coherence Tomography</intervention_name>
    <description>Additional optical coherence tomography (OCT) examination (during the already planned routine PCI procedure)</description>
    <arm_group_label>Patients from the VieCuri hospital</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        See 'Group descriptions'&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Group 1 - Protocol optimization: only additional PET-MRI&#xD;
&#xD;
          -  Diagnosed with stable angina pectoris and scheduled for a PCI procedure at the MUMC&#xD;
&#xD;
          -  Minimum age of 18 years&#xD;
&#xD;
          -  Mentally competent&#xD;
&#xD;
          -  Having provided informed written consent&#xD;
&#xD;
        Group 2 - Patients included at Viecuri hospital: additional PET-MRI and OCT&#xD;
&#xD;
          -  NSTEMI or STEMI patients who underwent urgent percutaneous coronary intervention (PCI)&#xD;
             of the culprit vessel, who are diagnosed with multivessel coronary disease and are&#xD;
             currently scheduled for a second PCI at the VieCuri hospital&#xD;
&#xD;
          -  Currently stable and scheduled for another PCI at the VieCuri hospital to stent&#xD;
             another coronary vessel&#xD;
&#xD;
          -  Able to visit the MUMC by own transport / train for PET-MR imaging before the new PCI&#xD;
             procedure&#xD;
&#xD;
          -  Minimum age of 18 years&#xD;
&#xD;
          -  Mentally competent&#xD;
&#xD;
          -  Having provided informed written consent&#xD;
&#xD;
        Group 3 - Patients included at MUMC+: additional PET-MRI&#xD;
&#xD;
          -  Recently diagnosed with NSTEMI and scheduled for a PCI at the MUMC&#xD;
&#xD;
          -  GRACE risk score between 90 and 140&#xD;
&#xD;
          -  Acute Coronary Syndrome (ACS) type 1&#xD;
&#xD;
          -  Minimum age of 18 years&#xD;
&#xD;
          -  Mentally competent&#xD;
&#xD;
          -  Having provided informed written consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Maastricht University Medical Centre</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>February 19, 2020</last_update_submitted>
  <last_update_submitted_qc>February 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Coronary Stenosis</mesh_term>
    <mesh_term>Infarction</mesh_term>
    <mesh_term>Ischemia</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/NCT03252990
org study id: NL58752.068.16
nct id: NCT03252990
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is designed as a prospective observational feasibility study. The investigators
      will study whether vulnerable plaques on OCT (fibrous cap ≤ 70 μm) show a locally increased
      uptake of 18F-choline on PET-MRI compared to stable plaques and whether the culprit plaque
      shows a locally increased uptake of 18F-choline on PET-MRI compared to non-culprit plaques.
      First, 15 NSTEMI or STEMI patients who underwent urgent percutaneous coronary intervention
      (PCI) of the culprit vessel, who are diagnosed with multivessel coronary disease and are
      currently scheduled for a second PCI at the VieCuri hospital will be included. These patients
      will be subjected to an additional 18F-choline PET-MRI examination at the MUMC+ and an
      additional optical coherence tomography (OCT) examination (during the PCI procedure at the
      Viecuri hospital). OCT will be performed as a reference standard to validate 18F-choline
      PET-MRI for detection of vulnerable plaques in the coronary arteries. In addition, 15 NSTEMI
      patients, who are scheduled for PCI of the culprit lesion at the MUMC+, will be subjected to
      an additional 18F-choline PET-MRI examination at the MUMC+. Hereby, the culprit coronary
      vessel and thereby the culprit plaque can be identified by the location of the myocardial
      infarct, as identified by late enhanced MRI. The investigators will study whether the culprit
      plaque shows an increased 18F-choline uptake on 18F-choline PET-MRI compared to non-culprit
      plaques in the other coronary arteries. All patients will receive standard, guideline-based
      clinical care, while PET-MRI and OCT will be performed as additional measurements. Before the
      start of the study, 5 stable angina pectoris patients that are scheduled for a PCI procedure
      at the MUMC+ will be included at the MUMC+ for a single PET-MRI scan to optimize the
      parameters of the coronary PET-MRI scan.
Background of the study:

      Myocardial infarction (MI) frequently recurs after MI, which may be related to insufficient
      vulnerable plaque identification using invasive coronary angiography. More accurate
      identification of vulnerable plaques may improve therapeutic strategies and clinical outcome.
      Recently, the investigators demonstrated that 18F-choline PET can be used to identify
      vulnerable carotid plaques. The investigators hypothesize that fully integrated 18F-choline
      PET-MRI enables detection of vulnerable coronary plaques.

      Objective of the study:

      The objective is to study the feasibility to detect vulnerable coronary plaques with
      18F-choline PET-MRI.

      Primary study parameters/outcome of the study:

        -  To investigate whether vulnerable plaques on OCT (fibrous cap ≤ 70 μm) show a locally
           increased uptake of 18F-choline on PET-MRI compared to stable plaques.

        -  To investigate whether the culprit plaque shows a locally increased uptake of
           18F-choline on PET-MRI compared to non-culprit plaques.

      Secondary study parameters/outcome of the study (if applicable):

        -  To study whether there is a correlation between the uptake of 18F-choline in coronary
           plaques and the degree of stenosis as shown on the angiogram acquired during the PCI
           procedure

        -  To study whether there is a correlation between the uptake of 18F-choline in coronary
           plaques and the presence of macrophages, micro-calcifications, lipid-rich necrotic core
           on OCT

        -  To investigate whether there is an association between the uptake of 18F-choline in the
           coronary arteries and that in the carotid arteries.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness (if applicable):

      This study will not delay any necessary treatment and the study is not expected to adversely
      affect outcome. The patients from the VieCuri will need to visit the MUMC for the additional
      PET-MRI scan. All patients in this study, including the 5 patients for protocol optimisation,
      will receive an average radiation dose of 5.3 mSv (0.019 mSv/MBq [see attachment 1], 280 MBq,
      average body weight 70 kg) and a maximum radiation dose of 6.8 mSv (360 MBq, ≥ 90 kg body
      weight) from the 18F-choline tracer. PET-MRI, Gadolinium and 18F-choline are safe and the
      risk of adverse effects are low (as described in chapter 7). The additional OCT examination
      is performed during the PCI procedure (only in the 15 patients of the VieCuri hospital), that
      is part of standard patient care, and carries the same risks as the PCI procedure, including:
      coronary dissection, air embolism, coronary thrombus, contrast nephropathy, contrast allergy,
      cardiovascular event, and death (extremely rare). These risks will be minimized by the use of
      heparin to achieve an Activating Clotting Time (ACT) value of 300, taking care of meticulous
      positioning of the wire and using the OCT catheter under fluoroscopy guidance. Approximately
      15% of the amount of contrast agent that is used during an PCI procedure will be additionally
      administered during the OCT procedure and 30 seconds of additional fluoroscopy guidance with
      associated increase in ionizing radiation dose will be used for positioning of the OCT
      catheter. During the additional PET- MRI and OCT examinations, there is a chance on
      accidental medical findings. These findings will be reported to the treating physician and
      the general practitioner of the patient. Study results are expected to contribute to
      improvement of vulnerable plaque detection for future patients.
observational model: Cohort
time perspective: Cross-Sectional
measure: To investigate whether vulnerable plaques on OCT (fibrous cap ≤ 70 μm) show a locally increased uptake of 18F-choline on PET-MRI compared to stable plaques.
time frame: 72 hours
measure: To investigate whether the culprit plaque shows a locally increased uptake of 18F-choline on PET-MRI compared to non-culprit plaques.
time frame: 72 hours
measure: To study whether there is a correlation between the uptake of 18F-choline in coronary plaques and the degree of stenosis as shown on the angiogram acquired during the PCI procedure
time frame: 72 hours
measure: To study whether there is a correlation between the uptake of 18F-choline in coronary plaques and the presence of macrophages, micro-calcifications, lipid-rich necrotic core on OCT
time frame: 72 hours
measure: To investigate whether there is an association between the uptake of 18F-choline in the coronary arteries and that in the carotid arteries.
time frame: 1.5 hours
arm group label: Optimization subjects
description: Before the enrollment of the actual study subjects, 5 stable angina pectoris patients that are scheduled for a PCI procedure at the MUMC+ will be included at the MUMC+ for a single PET-MRI scan to optimize the parameters of the coronary PET-MRI scan. All patients will receive standard, guideline-based clinical care, while PET-MRI will be performed as an additional measurement.
arm group label: Patients from the VieCuri hospital
description: 15 NSTEMI or STEMI patients who underwent urgent percutaneous coronary intervention (PCI) of the culprit vessel, who are diagnosed with multivessel coronary disease and are currently scheduled for a second PCI at the VieCuri hospital will be included. These patients will be subjected to an additional 18F-choline PET-MRI examination at the MUMC+ and an additional optical coherence tomography (OCT) examination (during the PCI procedure) at the Viecuri hospital. OCT will be performed as a reference standard to validate 18F-choline PET-MRI for detection of vulnerable plaques in the coronary arteries. All patients will receive standard, guideline-based clinical care, while PET-MRI and OCT will be performed as additional measurements.
intervention type: Diagnostic Test
intervention name: PET-MRI
description: Additional 18F-choline PET-MRI examination
arm group label: Optimization subjects
arm group label: Patients from the VieCuri hospital
intervention type: Procedure
intervention name: Optical Coherence Tomography
description: Additional optical coherence tomography (OCT) examination (during the already planned routine PCI procedure)
arm group label: Patients from the VieCuri hospital
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Myocardial Infarction
mesh term: Atherosclerosis
mesh term: Coronary Stenosis
mesh term: Infarction
mesh term: Ischemia
sharing ipd: No