<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/NCT03021577</url>
  </required_header>
  <id_info>
    <org_study_id>AAAQ9267</org_study_id>
    <nct_id>NCT03021577</nct_id>
  </id_info>
  <brief_title>Comparison of Orbital Versus Rotational Atherectomy Effects On Coronary Microcirculation in PCI</brief_title>
  <acronym>ORACLE</acronym>
  <official_title>Comparison of Orbital Versus Rotational Atherectomy Effects On Coronary Microcirculation in Percutaneous Coronary Intervention (PCI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Columbia 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that the orbital atherectomy system (OAS), a newer generation&#xD;
      atherectomy device, reduces the incidence of microcirculatory compromise as compared to older&#xD;
      generation rotational atherectomy (RA) due to differences in the mechanism of&#xD;
      athero-ablation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The presence of heavily calcified coronary lesions necessitates the use of ablative devices&#xD;
      that aid in successful percutaneous coronary intervention (PCI). However, atherectomy devices&#xD;
      generate microparticles that embolize to the distal coronary microcirculation and may&#xD;
      compromise myocardial tissue perfusion.&#xD;
&#xD;
      Two mechanisms that deserve particular attention are the eccentric mounting of the OAS crown&#xD;
      and the higher flow rates on the vasodilator flush. Firstly, as opposed to rotational&#xD;
      atherectomy where the larger, centrally mounted burr may cause obstruction of flow during the&#xD;
      atherectomy, the smaller eccentrically mounted crown in OAS allows continuous perfusion&#xD;
      during both atherectomy as well as rest periods. Second, both during rest and atherectomy,&#xD;
      the flow rates of vasodilatory flush is higher in OAS compared to RA. Combined, these&#xD;
      differences in coronary and vasodilator flush flow could lead to improved perfusion of the&#xD;
      distal circulation, particularly during the atherectomy runs when risk of embolization is&#xD;
      highest.&#xD;
&#xD;
      The loss of microcirculatory function can be transient, with partial or complete restoration&#xD;
      of microcirculatory blood flow, or permanent. As shown in studies of patients with acute&#xD;
      coronary syndromes, the loss of microcirculatory function is a critical and independent&#xD;
      predictor of myocardial recovery and adverse outcomes. The putative protective effects of OAS&#xD;
      on coronary microvasculature may therefore be of major clinical significance and impact.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2017</start_date>
  <completion_date type="Actual">March 16, 2019</completion_date>
  <primary_completion_date type="Actual">March 16, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Index of microcirculatory resistance (IMR)</measure>
    <time_frame>Up to 1 hour</time_frame>
    <description>Index of Microvascular Resistance (IMR) is defined as the distal coronary pressure multiplied by the hyperaemic mean transit time. IMR = Pd x Tmn at maximal hyperemia. This is for micro vascular function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Creatinine Kinase (CKMB) level</measure>
    <time_frame>1 hour</time_frame>
    <description>Blood test that helps determine incidence of peri-PCI myonecrosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Troponin I level</measure>
    <time_frame>1 hour</time_frame>
    <description>Blood test that helps determine incidence of peri-PCI myonecrosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fractional flow reserve (FFR)</measure>
    <time_frame>Up to 1 hour</time_frame>
    <description>FFR is defined as the ratio of (i.e.,percent of normal) flow in the stenotic artery to the flow in the same artery in the theoretic absence of the stenosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coronary flow reserve (CFR)</measure>
    <time_frame>Up to 1 hour</time_frame>
    <description>Coronary Flow Reserve (CFR) is the ratio between hyperemic and basal coronary flow. CFR=Hyperemic Flow /Resting Flow. This is for micro vascular function.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Coronary Artery Disease (CAD)</condition>
  <arm_group>
    <arm_group_label>Orbital Atherectomy System (OAS) Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to OAS. In a subset of patients (n= 20) a baseline cardiac magnetic Resonance Imaging (MRI) scan will be performed prior to PCI and repeated 24 hours after PCI to quantify the total volume of myocardial necrosis secondary to PCI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rotational Atherectomy (RA) Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to RA using the Rotablator Rotational Atherectomy System. In a subset of patients (n= 20) a baseline cardiac magnetic Resonance Imaging (MRI) scan will be performed prior to PCI and repeated 24 hours after PCI to quantify the total volume of myocardial necrosis secondary to PCI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Orbital Atherectomy System (OAS)</intervention_name>
    <description>The Cardiovascular Systems, Inc. (CSI) Diamondback 360 Coronary Orbital Atherectomy System (OAS) is a catheter-based system designed for facilitating stent delivery in patients with coronary artery lesions. The OAS consists of the hand-held CSI DIAMONDBACK 360 Coronary Orbital Atherectomy Device (OAD), the CSI Saline Infusion Pump (OAS pump), the CSI ViperWire Advance Coronary Guide Wire (VIPERWIRE guide wire), and the CSI ViperSlide Lubricant.</description>
    <arm_group_label>Orbital Atherectomy System (OAS) Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Rotablator Rotational Atherectomy System</intervention_name>
    <description>The Rotablator Rotational Atherectomy System is comprised of a Rotablator RotaGlide, a Rotablator RotaLink Plus/RotaWire/Console</description>
    <arm_group_label>Rotational Atherectomy (RA) Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance Imaging (MRI)</intervention_name>
    <description>In a subset of patients (n= 20) a baseline cardiac MRI will be performed prior to PCI and repeated 24 hours after PCI to quantify the total volume of myocardial necrosis secondary to PCI.</description>
    <arm_group_label>Orbital Atherectomy System (OAS) Group</arm_group_label>
    <arm_group_label>Rotational Atherectomy (RA) Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years&#xD;
&#xD;
          2. Patient with an indication for PCI including:&#xD;
&#xD;
               -  Angina (stable or unstable),&#xD;
&#xD;
               -  Silent ischemia (a visually estimated target lesion diameter stenosis of ≥70%, a&#xD;
                  positive non-invasive stress test, or FFR ≤0.80 must be present),&#xD;
&#xD;
               -  Non-ST Segment Elevation Myocardial Infarction (NSTEMI)&#xD;
&#xD;
          3. Patients will undergo cardiac catheterization and possible or definite PCI with intent&#xD;
             to stent using any non-investigational metallic drug-eluting stent (DES)&#xD;
&#xD;
          4. Signed written informed consent&#xD;
&#xD;
          5. Heavily calcified (severe)lesions necessitating atherectomy.&#xD;
&#xD;
        Angiographic inclusion criteria:&#xD;
&#xD;
          1. The target lesion must be located in a native coronary artery with visually estimated&#xD;
             reference vessel diameter of ≥2.25 mm to ≤4.00 mm.&#xD;
&#xD;
          2. Lesion length between 20 mm and 50mm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Estimated creatinine clearance &lt;30 ml/min using Cockcroft-Gault equation, unless the&#xD;
             patient is on dialysis;&#xD;
&#xD;
          2. ST-elevation Myocardial Infarction (STEMI) within 24 hours of initial time of&#xD;
             presentation to the first treating hospital, whether at a transfer facility or the&#xD;
             study hospital.&#xD;
&#xD;
          3. PCI within 24 hours preceding the study procedure.&#xD;
&#xD;
          4. Cardiogenic shock (defined as persistent hypotension (systolic blood pressure &lt;90&#xD;
             mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support,&#xD;
             including intra-aortic balloon pump (IABP), at time of procedure.&#xD;
&#xD;
          5. Mobitz II second degree or complete heart block&#xD;
&#xD;
          6. Malignant ventricular arrhythmias requiring treatment&#xD;
&#xD;
          7. Pulmonary edema defined as patient with shortness of breath, evidence of volume&#xD;
             overload on physical exam, and crepitations on physical exam (&gt;1/3 of lungs) or&#xD;
             radiographic interstitial or alveolar pulmonary edema&#xD;
&#xD;
          8. Subject is intubated.&#xD;
&#xD;
          9. Known left ventricular ejection fraction (LVEF) &lt;35%.&#xD;
&#xD;
         10. Severe valvular disease (e.g. severe mitral regurgitation or severe aortic stenosis)&#xD;
&#xD;
         11. Patient is participating in any other investigational drug or device clinical trial&#xD;
             that has not reached its primary endpoint.&#xD;
&#xD;
         12. Women who are pregnant or breastfeeding (women of child-bearing potential must have a&#xD;
             negative pregnancy test within one week before treatment).&#xD;
&#xD;
        General Inclusion - MRI Sub-Study&#xD;
&#xD;
          1. Patients with no prior MI/scarring in the subtended myocardial territory.&#xD;
&#xD;
          2. Patients with no contraindication for MRI studies&#xD;
&#xD;
          3. Patients who could safely receive Gadolinium (i.e. estimated glomerular filtration&#xD;
             rate (eGFR) &gt;30)&#xD;
&#xD;
        Angiographic Exclusion Criteria:&#xD;
&#xD;
          1. Lesion length &lt;20mm&#xD;
&#xD;
          2. Study target lesion in a bypass graft&#xD;
&#xD;
          3. Ostial right coronary artery (RCA) study target lesion&#xD;
&#xD;
          4. Chronic total occlusion (Thrombolysis In Myocardial Infarction (TIMI) flow 0/1) study&#xD;
             target lesion&#xD;
&#xD;
          5. Bifurcation study lesion with a planned dual stent strategy&#xD;
&#xD;
          6. In-stent restenosis study target lesion&#xD;
&#xD;
        General Inclusion - MRI Sub-Study&#xD;
&#xD;
          1. Patients with no prior myocardial infarction (MI)/scarring in the subtended myocardial&#xD;
             territory.&#xD;
&#xD;
          2. Patients with no contraindication for Magnetic resonance imaging (MRI) studies&#xD;
&#xD;
          3. Patients who could safely receive Gadolinium (i.e. eGFR&gt;30)&#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>Ziad A. Ali, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>March 22, 2019</last_update_submitted>
  <last_update_submitted_qc>March 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Ziad Ali</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>orbital atherectomy system</keyword>
  <keyword>rotational atherectomy</keyword>
  <keyword>Fractional flow reserve</keyword>
  <keyword>coronary flow reserve</keyword>
  <keyword>index of microcirculatory resistance (IMR)</keyword>
  <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>
  <pending_results>
    <submitted>March 17, 2020</submitted>
    <returned>March 27, 2020</returned>
    <submitted>April 1, 2020</submitted>
    <returned>April 13, 2020</returned>
  </pending_results>
  <!-- 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/NCT03021577
org study id: AAAQ9267
nct id: NCT03021577
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The investigators hypothesize that the orbital atherectomy system (OAS), a newer generation
      atherectomy device, reduces the incidence of microcirculatory compromise as compared to older
      generation rotational atherectomy (RA) due to differences in the mechanism of
      athero-ablation.
The presence of heavily calcified coronary lesions necessitates the use of ablative devices
      that aid in successful percutaneous coronary intervention (PCI). However, atherectomy devices
      generate microparticles that embolize to the distal coronary microcirculation and may
      compromise myocardial tissue perfusion.

      Two mechanisms that deserve particular attention are the eccentric mounting of the OAS crown
      and the higher flow rates on the vasodilator flush. Firstly, as opposed to rotational
      atherectomy where the larger, centrally mounted burr may cause obstruction of flow during the
      atherectomy, the smaller eccentrically mounted crown in OAS allows continuous perfusion
      during both atherectomy as well as rest periods. Second, both during rest and atherectomy,
      the flow rates of vasodilatory flush is higher in OAS compared to RA. Combined, these
      differences in coronary and vasodilator flush flow could lead to improved perfusion of the
      distal circulation, particularly during the atherectomy runs when risk of embolization is
      highest.

      The loss of microcirculatory function can be transient, with partial or complete restoration
      of microcirculatory blood flow, or permanent. As shown in studies of patients with acute
      coronary syndromes, the loss of microcirculatory function is a critical and independent
      predictor of myocardial recovery and adverse outcomes. The putative protective effects of OAS
      on coronary microvasculature may therefore be of major clinical significance and impact.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Index of microcirculatory resistance (IMR)
time frame: Up to 1 hour
description: Index of Microvascular Resistance (IMR) is defined as the distal coronary pressure multiplied by the hyperaemic mean transit time. IMR = Pd x Tmn at maximal hyperemia. This is for micro vascular function.
measure: Creatinine Kinase (CKMB) level
time frame: 1 hour
description: Blood test that helps determine incidence of peri-PCI myonecrosis.
measure: Troponin I level
time frame: 1 hour
description: Blood test that helps determine incidence of peri-PCI myonecrosis.
measure: Fractional flow reserve (FFR)
time frame: Up to 1 hour
description: FFR is defined as the ratio of (i.e.,percent of normal) flow in the stenotic artery to the flow in the same artery in the theoretic absence of the stenosis.
measure: Coronary flow reserve (CFR)
time frame: Up to 1 hour
description: Coronary Flow Reserve (CFR) is the ratio between hyperemic and basal coronary flow. CFR=Hyperemic Flow /Resting Flow. This is for micro vascular function.
arm group label: Orbital Atherectomy System (OAS) Group
arm group type: Active Comparator
description: Subjects randomized to OAS. In a subset of patients (n= 20) a baseline cardiac magnetic Resonance Imaging (MRI) scan will be performed prior to PCI and repeated 24 hours after PCI to quantify the total volume of myocardial necrosis secondary to PCI.
arm group label: Rotational Atherectomy (RA) Group
arm group type: Active Comparator
description: Subjects randomized to RA using the Rotablator Rotational Atherectomy System. In a subset of patients (n= 20) a baseline cardiac magnetic Resonance Imaging (MRI) scan will be performed prior to PCI and repeated 24 hours after PCI to quantify the total volume of myocardial necrosis secondary to PCI.
intervention type: Device
intervention name: Orbital Atherectomy System (OAS)
description: The Cardiovascular Systems, Inc. (CSI) Diamondback 360 Coronary Orbital Atherectomy System (OAS) is a catheter-based system designed for facilitating stent delivery in patients with coronary artery lesions. The OAS consists of the hand-held CSI DIAMONDBACK 360 Coronary Orbital Atherectomy Device (OAD), the CSI Saline Infusion Pump (OAS pump), the CSI ViperWire Advance Coronary Guide Wire (VIPERWIRE guide wire), and the CSI ViperSlide Lubricant.
arm group label: Orbital Atherectomy System (OAS) Group
intervention type: Device
intervention name: Rotablator Rotational Atherectomy System
description: The Rotablator Rotational Atherectomy System is comprised of a Rotablator RotaGlide, a Rotablator RotaLink Plus/RotaWire/Console
arm group label: Rotational Atherectomy (RA) Group
intervention type: Procedure
intervention name: Magnetic Resonance Imaging (MRI)
description: In a subset of patients (n= 20) a baseline cardiac MRI will be performed prior to PCI and repeated 24 hours after PCI to quantify the total volume of myocardial necrosis secondary to PCI.
arm group label: Orbital Atherectomy System (OAS) Group
arm group label: Rotational Atherectomy (RA) Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ziad A. Ali, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Ziad Ali
investigator title: Assistant Professor of Medicine
mesh term: Coronary Artery Disease
sharing ipd: No
submitted: March 17, 2020
returned: March 27, 2020
submitted: April 1, 2020
returned: April 13, 2020