<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/NCT01676207</url>
  </required_header>
  <id_info>
    <org_study_id>007/12</org_study_id>
    <nct_id>NCT01676207</nct_id>
  </id_info>
  <brief_title>Prevalence of Extracardiac Coronary Collateral Supply Via the Internal Mammary Arteries</brief_title>
  <official_title>Prevalence of Extracardiac Coronary Collateral Supply Via the Internal Mammary Arteries</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In contrast to the extensively studied coronary collateral circulation within the heart,&#xD;
      clinical attention has been paid only anecdotally to extracardiac-to-coronary anastomoses.&#xD;
      Usually this has been in the form of case reports giving account of angiographically visible&#xD;
      anastomoses between the coronary circulation and the internal mammary artery (IMA), typically&#xD;
      in the presence of a chronic occlusion of a coronary artery. In the anatomical literature,the&#xD;
      most common types of extracardiac anastomoses include bronchial-to-coronary-artery and&#xD;
      IMA-to-coronary-artery connections. Anastomoses between the IMA and the coronary circulation&#xD;
      have been documented to occur in 12% of post-mortem patients with CAD.&#xD;
&#xD;
      Importantly, hitherto existing observations typically have relied on visual methods&#xD;
      insensitive for the adequate detection especially of structurally present but poorly&#xD;
      functional anastomoses. On a diagnostic coronary angiogram, collaterals are visible only if&#xD;
      the recipient vessel is subtotally stenotic or fully occluded, or can be rendered visible&#xD;
      during coronary spasm or by temporary balloon occlusion of the recipient artery and&#xD;
      simultaneous injection of contrast medium into the other arteries, respectively. Similarly,&#xD;
      the macroscopic pathologic postmortem examination is likely to underestimate the true number&#xD;
      of extracardiac coronary collaterals.&#xD;
&#xD;
      The purpose of this study is to determine the in vivo prevalence and functional distribution&#xD;
      of IMA-to-coronary collateral supply via both the right and the left coronary artery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Surgical bypass creates an artificial anastomosis between a diseased coronary artery and an&#xD;
      extracardiac vessel. Often one of the internal mammary arteries (IMA) is used for this&#xD;
      procedure. These connections have been very rarely described to occur naturally, representing&#xD;
      extracardiac coronary collaterals.&#xD;
&#xD;
      In contrast to the extensively studied coronary collateral circulation within the heart,&#xD;
      clinical attention has been paid only anecdotally to extracardiac-to-coronary anastomoses.&#xD;
      Usually this has been in the form of case reports giving account of angiographically visible&#xD;
      anastomoses between the coronary circulation and the internal mammary artery (IMA), typically&#xD;
      in the presence of a chronic occlusion of a coronary artery. In the anatomical literature,the&#xD;
      most common types of extracardiac anastomoses include bronchial-to-coronary-artery and&#xD;
      IMA-to-coronary-artery connections. Anastomoses between the IMA and the coronary circulation&#xD;
      have been documented to occur in 12% of post-mortem patients with CAD.&#xD;
&#xD;
      Importantly, hitherto existing observations typically have relied on visual methods&#xD;
      insensitive for the adequate detection especially of structurally present but poorly&#xD;
      functional anastomoses. On a diagnostic coronary angiogram, collaterals are visible only if&#xD;
      the recipient vessel is subtotally stenotic or fully occluded, or can be rendered visible&#xD;
      during coronary spasm or by temporary balloon occlusion of the recipient artery and&#xD;
      simultaneous injection of contrast medium into the other arteries, respectively. Similarly,&#xD;
      the macroscopic pathologic postmortem examination is likely to underestimate the true number&#xD;
      of extracardiac coronary collaterals.&#xD;
&#xD;
      When present, pre-existing connections between the IMA and the coronary circulation could be&#xD;
      promoted to serve as natural bypasses to diseased coronary arteries. Promotion of&#xD;
      extracardiac blood flow to the coronary circulation has very rarely already been attempted in&#xD;
      the past. In a minimally invasive intervention, bilateral surgical ligation of both IMA was&#xD;
      performed in a few patients, resulting in clinical improvement and disappearance of angina.&#xD;
      However, with the advent of coronary surgery, efforts aimed at promotion of naturally&#xD;
      existing bypasses have been abandoned for the placing of artificially created extracardiac&#xD;
      anastomoses to the coronary circulation.&#xD;
&#xD;
      Yet with the limitations of these established revascularization interventions becoming clear,&#xD;
      the need to search for alternative treatment options gets evident. Therapeutic arteriogenesis&#xD;
      with promotion of naturally existing bypasses between the coronary circulation and the&#xD;
      internal mammary arteries presents a future possibility.&#xD;
&#xD;
      Objective&#xD;
&#xD;
      The purpose of this study is to determine the in vivo prevalence and functional distribution&#xD;
      of IMA-to-coronary collateral supply via both the right and the left coronary artery.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Comparative observational study with CFI measurements in the IMAs (proximal IMA occlusion)&#xD;
      and in the coronary circulation (distal IMA occlusion), and IMA angiography during distal IMA&#xD;
      occlusion.&#xD;
&#xD;
      Study Protocol&#xD;
&#xD;
        -  Diagnostic coronary angiography and LV angiography&#xD;
&#xD;
        -  Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate&#xD;
&#xD;
        -  Right and left IMA CFI during a 1-minute ostial vessel occlusion&#xD;
&#xD;
        -  Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or&#xD;
           according to ease of access by the pressure sensor wire. Placement of a non-sensor wire&#xD;
           in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the&#xD;
           second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right&#xD;
           IMA. Two coronary CFI measurements: the first with, the second without distal IMA&#xD;
           balloon occlusion.&#xD;
&#xD;
        -  IMA angiography (left and right) during distal IMA and coronary occlusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</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>Coronary Collateral Flow Index (CFI)</measure>
    <time_frame>during coronary artery balloon occlusion</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intra-coronary occlusive ECG ST segment shift (mV)</measure>
    <time_frame>at 1 minute of coronary artery balloon occlusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>angiographic visibility of coronary collateral supply via the internal mammary artery during their distal balloon occlusion</measure>
    <time_frame>at 1 minute of coronary artery balloon occlusion</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">120</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Collateral Circulation</condition>
  <condition>Ischemia</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <description>CAD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <description>no CAD</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Coronary Angiography with collateral flow measurements</intervention_name>
    <description>Diagnostic coronary angiography and LV angiography&#xD;
Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate&#xD;
Right and left IMA CFI during a 1-minute ostial vessel occlusion&#xD;
Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.&#xD;
IMA angiography (left and right) during distal IMA and coronary occlusion.</description>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Coronary Angiography with collateral flow measurements</intervention_name>
    <description>Diagnostic coronary angiography and LV angiography&#xD;
Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate&#xD;
Right and left IMA CFI during a 1-minute ostial vessel occlusion&#xD;
Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.&#xD;
IMA angiography (left and right) during distal IMA and coronary occlusion.</description>
    <arm_group_label>2</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients electively referred for coronary angiography&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt; 17 years&#xD;
&#xD;
          -  electively referred for coronary angiography&#xD;
&#xD;
          -  written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Acute coronary syndrome&#xD;
&#xD;
          -  Prior coronary artery bypass grafting&#xD;
&#xD;
          -  Severe cardiac valve disease&#xD;
&#xD;
          -  Congestive heart failure NYHA III-IV&#xD;
&#xD;
          -  Severe pulmonary artery hypertension&#xD;
&#xD;
          -  Severe hepatic or renal failure (creatinine clearance &lt; 15ml/min)&#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>Christian Seiler, MD Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Cardiology, Bern University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Cardiology, Bern University Hospital</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>January 15, 2014</last_update_submitted>
  <last_update_submitted_qc>January 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>coronary collateral circulation</keyword>
  <keyword>extracardiac coronary collaterals</keyword>
  <keyword>coronary artery disease</keyword>
  <keyword>coronary circulation</keyword>
  <keyword>internal mammary artery</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>Ischemia</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/NCT01676207
org study id: 007/12
nct id: NCT01676207
lead sponsor: 
has dmc: No
In contrast to the extensively studied coronary collateral circulation within the heart,
      clinical attention has been paid only anecdotally to extracardiac-to-coronary anastomoses.
      Usually this has been in the form of case reports giving account of angiographically visible
      anastomoses between the coronary circulation and the internal mammary artery (IMA), typically
      in the presence of a chronic occlusion of a coronary artery. In the anatomical literature,the
      most common types of extracardiac anastomoses include bronchial-to-coronary-artery and
      IMA-to-coronary-artery connections. Anastomoses between the IMA and the coronary circulation
      have been documented to occur in 12% of post-mortem patients with CAD.

      Importantly, hitherto existing observations typically have relied on visual methods
      insensitive for the adequate detection especially of structurally present but poorly
      functional anastomoses. On a diagnostic coronary angiogram, collaterals are visible only if
      the recipient vessel is subtotally stenotic or fully occluded, or can be rendered visible
      during coronary spasm or by temporary balloon occlusion of the recipient artery and
      simultaneous injection of contrast medium into the other arteries, respectively. Similarly,
      the macroscopic pathologic postmortem examination is likely to underestimate the true number
      of extracardiac coronary collaterals.

      The purpose of this study is to determine the in vivo prevalence and functional distribution
      of IMA-to-coronary collateral supply via both the right and the left coronary artery.
Background

      Surgical bypass creates an artificial anastomosis between a diseased coronary artery and an
      extracardiac vessel. Often one of the internal mammary arteries (IMA) is used for this
      procedure. These connections have been very rarely described to occur naturally, representing
      extracardiac coronary collaterals.

      In contrast to the extensively studied coronary collateral circulation within the heart,
      clinical attention has been paid only anecdotally to extracardiac-to-coronary anastomoses.
      Usually this has been in the form of case reports giving account of angiographically visible
      anastomoses between the coronary circulation and the internal mammary artery (IMA), typically
      in the presence of a chronic occlusion of a coronary artery. In the anatomical literature,the
      most common types of extracardiac anastomoses include bronchial-to-coronary-artery and
      IMA-to-coronary-artery connections. Anastomoses between the IMA and the coronary circulation
      have been documented to occur in 12% of post-mortem patients with CAD.

      Importantly, hitherto existing observations typically have relied on visual methods
      insensitive for the adequate detection especially of structurally present but poorly
      functional anastomoses. On a diagnostic coronary angiogram, collaterals are visible only if
      the recipient vessel is subtotally stenotic or fully occluded, or can be rendered visible
      during coronary spasm or by temporary balloon occlusion of the recipient artery and
      simultaneous injection of contrast medium into the other arteries, respectively. Similarly,
      the macroscopic pathologic postmortem examination is likely to underestimate the true number
      of extracardiac coronary collaterals.

      When present, pre-existing connections between the IMA and the coronary circulation could be
      promoted to serve as natural bypasses to diseased coronary arteries. Promotion of
      extracardiac blood flow to the coronary circulation has very rarely already been attempted in
      the past. In a minimally invasive intervention, bilateral surgical ligation of both IMA was
      performed in a few patients, resulting in clinical improvement and disappearance of angina.
      However, with the advent of coronary surgery, efforts aimed at promotion of naturally
      existing bypasses have been abandoned for the placing of artificially created extracardiac
      anastomoses to the coronary circulation.

      Yet with the limitations of these established revascularization interventions becoming clear,
      the need to search for alternative treatment options gets evident. Therapeutic arteriogenesis
      with promotion of naturally existing bypasses between the coronary circulation and the
      internal mammary arteries presents a future possibility.

      Objective

      The purpose of this study is to determine the in vivo prevalence and functional distribution
      of IMA-to-coronary collateral supply via both the right and the left coronary artery.

      Methods

      Comparative observational study with CFI measurements in the IMAs (proximal IMA occlusion)
      and in the coronary circulation (distal IMA occlusion), and IMA angiography during distal IMA
      occlusion.

      Study Protocol

        -  Diagnostic coronary angiography and LV angiography

        -  Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate

        -  Right and left IMA CFI during a 1-minute ostial vessel occlusion

        -  Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or
           according to ease of access by the pressure sensor wire. Placement of a non-sensor wire
           in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the
           second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right
           IMA. Two coronary CFI measurements: the first with, the second without distal IMA
           balloon occlusion.

        -  IMA angiography (left and right) during distal IMA and coronary occlusion.
observational model: Cohort
time perspective: Cross-Sectional
measure: Coronary Collateral Flow Index (CFI)
time frame: during coronary artery balloon occlusion
measure: Intra-coronary occlusive ECG ST segment shift (mV)
time frame: at 1 minute of coronary artery balloon occlusion
measure: angiographic visibility of coronary collateral supply via the internal mammary artery during their distal balloon occlusion
time frame: at 1 minute of coronary artery balloon occlusion
arm group label: 1
description: CAD
arm group label: 2
description: no CAD
intervention type: Procedure
intervention name: Coronary Angiography with collateral flow measurements
description: Diagnostic coronary angiography and LV angiography
Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate
Right and left IMA CFI during a 1-minute ostial vessel occlusion
Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.
IMA angiography (left and right) during distal IMA and coronary occlusion.
arm group label: 1
intervention type: Procedure
intervention name: Coronary Angiography with collateral flow measurements
description: Diagnostic coronary angiography and LV angiography
Administration of 5'000 units of heparin i.v. and 2 puffs of oral isosorbide-dinitrate
Right and left IMA CFI during a 1-minute ostial vessel occlusion
Selection of the coronary artery for CFI according to stenotic lesion chosen for PCI or according to ease of access by the pressure sensor wire. Placement of a non-sensor wire in the left IMA. Two coronary CFI measurements (1-minute occlusion): the first with, the second without distal IMA balloon occlusion. Placement of a non-sensor wire in the right IMA. Two coronary CFI measurements: the first with, the second without distal IMA balloon occlusion.
IMA angiography (left and right) during distal IMA and coronary occlusion.
arm group label: 2
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christian Seiler, MD Prof
role: Principal Investigator
affiliation: Department of Cardiology, Bern University Hospital
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Ischemia