<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/NCT01675440</url>
  </required_header>
  <id_info>
    <org_study_id>10050361DOC</org_study_id>
    <nct_id>NCT01675440</nct_id>
  </id_info>
  <brief_title>Safety &amp; Efficacy Study of the Medtronic CoreValve® System-Treatment of Symptomatic Severe Aortic Stenosis With Significant Comorbidities in Extreme Risk Subjects Who Need Aortic Valve Replacement</brief_title>
  <official_title>Medtronic CoreValve® U.S. Expanded Use Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medtronic Cardiovascular</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medtronic Cardiovascular</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety and efficacy of the Medtronic CoreValve® System for the treatment of&#xD;
      symptomatic severe aortic stenosis in subjects with significant comorbidities in whom the&#xD;
      risk of surgical aortic valve replacement has a predicted operative mortality or serious,&#xD;
      irreversible morbidity risk of ≥50% at 30 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of the study is to evaluate the safety and effectiveness of the&#xD;
      Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme Risk&#xD;
      Pivotal Trial population due to one or more additional co-morbidities, as measured by a&#xD;
      composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic&#xD;
      severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled&#xD;
      in this study have a predicted operative mortality or serious, irreversible morbidity risk of&#xD;
      ≥50% at 30 days associated with surgical aortic valve replacement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">January 2026</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>All-cause Mortality or Major stroke</measure>
    <time_frame>12 months</time_frame>
    <description>All-cause Mortality or Major Stroke</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) Event Rate</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>MACCE is defined as a composite of: • All-Cause Death • Myocardial Infarction (MI) • All Stroke • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Occurrence of individual MACCE Components</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>Individual MACCE Components Include: - All Cause Mortality - MI - All stroke - Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major Adverse Events (MAEs)</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>MAEs Include: •MACCE •Acute Kidney Injury •Cardiac Tamponade •Prosthetic Valve Dysfunction •Cardiogenic Shock •Valve Endocarditis •Life-Threatening, Disabling or Major Bleeding •Major Vascular Complication •Cardiac Perforation •Device Migration/Valve Embolism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Conduction Disturbance Requiring Permanent Pacemaker Implantation</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>The incidence of conduction disturbance requiring permanent pacemaker implantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NYHA Class</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline</measure>
    <time_frame>30 days and 12 months</time_frame>
    <description>Change in distance walked during 6MWT from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of Days Alive Out of Hospital Versus Total Days Alive</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (QoL) Change from Baseline</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>QoL change from baseline using the following measures: •Kansas City Cardiomyopathy Questionnaire (KCCQ) •SF-12 •EuroQoL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echocardiographic Assessment of Valve Performance</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>Using the following measures: • Transvalvular mean gradient • Effective orifice area (EOA) •degree of aortic valve regurgitation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aortic Valve Disease Hospitalization</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>The number of subjects re-hospitalized after the initial procedure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular Deaths and Valve-related Deaths</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>The number of cardiovascular deaths and valve-related deaths</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Strokes</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>The number of subjects with strokes and TIAs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Index Procedure Related Major Adverse Events (MAEs)</measure>
    <time_frame>Procedure</time_frame>
    <description>Index procedure-related MAE events will be summarized</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Index Procedure Hospital Stay</measure>
    <time_frame>Number of days from admission to discharge</time_frame>
    <description>The length of index procedure hospital stay will be summarized</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Device Success</measure>
    <time_frame>Number of days from admission to discharge</time_frame>
    <description>Defined as: 1) Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system, 2) Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function), 3) Intended performance of the prosthetic valve (aortic valve area &gt; 1.2 cm2 for 26, 29 and 31mm valves, ≥ 0.9 cm2 for 23mm valve (by echocardiography using the continuity equation) and mean aortic valve gradient &lt; 20 mmHg or peak velocity &lt; 3 m/sec, without moderate or severe prosthetic valve aortic regurgitation) 4) Only one valve implanted in the proper anatomical location. For TAV in SAV subjects, only # 1, 2 and 4 will be used to calculate device success.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedural Success</measure>
    <time_frame>Number of days from admission to discharge</time_frame>
    <description>Defined as device success and absence of in-hospital MACCE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evidence of Prosthetic Valve Dysfunction</measure>
    <time_frame>30 days, 6 months, 12 months and annually thereafter up to 5 years</time_frame>
    <description>PVD was defined according to VARC using the site reported echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met: •Peak velocity &gt; 4 m/s •Mean gradient &gt; 35 mmHg •EOA &lt; 0.8 cm2 •TVIV1 / TVIV2 &lt; 0.25</description>
  </secondary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Actual">782</enrollment>
  <condition>Severe Aortic Stenosis</condition>
  <arm_group>
    <arm_group_label>Severe (≥3-4+) Mitral Valve Regurgitation</arm_group_label>
    <description>Mitral valve regurgitation ≥3-4+</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Severe (≥3-4+) Tricuspid Valve Regurgitation</arm_group_label>
    <description>Tricuspid valve regurgitation ≥3-4+</description>
  </arm_group>
  <arm_group>
    <arm_group_label>End Stage Renal Disease (ESRD)</arm_group_label>
    <description>End stage renal disease requiring renal replacement therapy or a creatinine clearance (CRCL) &lt;20 cc/min, but not on dialysis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Gradient Low Output Aortic Stenosis</arm_group_label>
    <description>Low gradient low output aortic stenosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Failed Bioprosthetic Surgical Aortic Valve</arm_group_label>
    <description>Stenosed, insufficient or combined bioprosthetic surgical aortic valve failure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2 or More Conditions</arm_group_label>
    <description>2 or more of the listed conditions</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)</intervention_name>
    <arm_group_label>2 or More Conditions</arm_group_label>
    <arm_group_label>End Stage Renal Disease (ESRD)</arm_group_label>
    <arm_group_label>Failed Bioprosthetic Surgical Aortic Valve</arm_group_label>
    <arm_group_label>Low Gradient Low Output Aortic Stenosis</arm_group_label>
    <arm_group_label>Severe (≥3-4+) Mitral Valve Regurgitation</arm_group_label>
    <arm_group_label>Severe (≥3-4+) Tricuspid Valve Regurgitation</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects with symptomatic severe aortic stenosis requiring aortic valve replacement, with&#xD;
        predicted operative mortality or serious, irreversible morbidity risk of ≥ 50% at 30 days,&#xD;
        and at least one of the following conditions:&#xD;
&#xD;
          -  Severe (≥3-4+) mitral valve regurgitation&#xD;
&#xD;
          -  Severe (≥3-4+) tricuspid valve regurgitation&#xD;
&#xD;
          -  End stage renal disease (ESRD) requiring renal replacement therapy or creatinine&#xD;
             clearance &lt;20cc/min, but not requiring renal replacement therapy&#xD;
&#xD;
          -  Low gradient, low output aortic stenosis&#xD;
&#xD;
          -  Failed bioprosthetic surgical aortic valve&#xD;
&#xD;
          -  2 or more conditions (listed above)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject must have co-morbidities such that one cardiologist and two cardiac surgeons&#xD;
             agree that medical factors preclude operation, based on a conclusion that the&#xD;
             probability of death or serious morbidity exceeds the probability of meaningful&#xD;
             improvement. Specifically, the predicted operative risk of death or serious,&#xD;
             irreversible morbidity is ≥ 50% at 30 days.&#xD;
&#xD;
          -  Subjects must meet all of the criteria under at least one of the sub-groups 2a-c:&#xD;
&#xD;
             a. Senile degenerative aortic valve stenosis and i. At least one of the following&#xD;
             co-morbid conditions:&#xD;
&#xD;
               1. Severe (≥3-4+) mitral valve regurgitation as measured by echocardiography&#xD;
&#xD;
               2. Severe (≥3-4+) tricuspid valve regurgitation as measured by echocardiography&#xD;
&#xD;
               3. End-stage renal disease requiring renal replacement therapy (Stage 5 of the KDOQI&#xD;
                  CKD Classification) or creatinine clearance &lt;20cc/min but not requiring renal&#xD;
                  replacement therapy&#xD;
&#xD;
                  AND&#xD;
&#xD;
                  ii. mean gradient &gt; 40 mmHg or jet velocity greater than 4.0 m/sec by either&#xD;
                  resting or dobutamine stress echocardiogram (if the LVEF &lt; 50%), or simultaneous&#xD;
                  pressure recordings at cardiac catheterization either resting or with dobutamine&#xD;
                  stress (if the LVEF &lt; 50%) AND iii. an initial aortic valve area of ≤ 0.8 cm2 (or&#xD;
                  aortic valve area index ≤0.5 cm2/m2) by resting echocardiogram or simultaneous&#xD;
                  pressure recordings at cardiac catheterization&#xD;
&#xD;
                  AND/OR&#xD;
&#xD;
                  b. Low gradient, low output aortic stenosis as defined by the presence of all&#xD;
                  three of the following i. In the presence of LVEF &lt;50%, absence of contractile&#xD;
                  reserve, a mean gradient ≥25mmHg and &lt;40mmHg AND jet velocity less than 4.0m/sec&#xD;
                  with dobutamine stress echocardiography or simultaneous pressure recordings at&#xD;
                  cardiac catheterization OR In the presence of LVEF ≥50%, a mean gradient ≥25mmHg&#xD;
                  and &lt;40mmHg AND jet velocity less than 4.0 m/sec, by echocardiography or&#xD;
                  simultaneous pressure recordings at cardiac catheterization AND ii. an initial&#xD;
                  aortic valve area of ≤0.8 cm2 (or aortic valve area index ≤0.5 cm2/m2) by resting&#xD;
                  echocardiogram or simultaneous pressure recordings at cardiac catheterization AND&#xD;
                  iii. radiographic evidence of severe aortic valve calcification AND/OR c. Failed&#xD;
                  bioprosthetic surgical aortic valve&#xD;
&#xD;
          -  Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York&#xD;
             Heart Association (NYHA) Functional Class II or greater.&#xD;
&#xD;
          -  The subject or the subject's legal representative has been informed of the nature of&#xD;
             the study, agrees to its provisions and has provided written informed consent as&#xD;
             approved by the IRB of the respective clinical site.&#xD;
&#xD;
          -  The subject and the treating physician agree that the subject will return for all&#xD;
             required post-procedure follow-up visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Clinical&#xD;
&#xD;
          -  Evidence of an acute myocardial infarction ≤30 days before the MCS TAVI procedure.&#xD;
&#xD;
          -  Any percutaneous coronary or peripheral interventional procedure performed within 30&#xD;
             days prior to the MCS TAVI procedure&#xD;
&#xD;
          -  Blood dyscrasias as defined: leukopenia (WBC &lt;1000mm3), thrombocytopenia (platelet&#xD;
             count &lt;50,000 cells/mm3), history of bleeding diathesis or coagulopathy.&#xD;
&#xD;
          -  Untreated clinically significant coronary artery disease requiring revascularization.&#xD;
&#xD;
          -  Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or&#xD;
             mechanical hemodynamic support.&#xD;
&#xD;
          -  Need for emergency surgery for any reason.&#xD;
&#xD;
          -  Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) &lt;20% as&#xD;
             measured by resting echocardiogram.&#xD;
&#xD;
          -  Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack&#xD;
             (TIA).&#xD;
&#xD;
          -  Active Gastrointestinal (GI) bleeding that would preclude anticoagulation.&#xD;
&#xD;
          -  A known hypersensitivity or contraindication to all anticoagulation/antiplatelet&#xD;
             regimens (including ability to be anticoagulated for the index procedure), nitinol, or&#xD;
             [allergic] sensitivity to contrast media which cannot be adequately pre-medicated.&#xD;
&#xD;
          -  Ongoing sepsis, including active endocarditis.&#xD;
&#xD;
          -  Subject refuses a blood transfusion.&#xD;
&#xD;
          -  Life expectancy &lt;12 months due to associated non-cardiac co-morbid conditions.&#xD;
&#xD;
          -  Other medical, social, or psychological conditions that in the opinion of an&#xD;
             Investigator precludes the subject from appropriate consent.&#xD;
&#xD;
          -  Severe dementia (resulting in either inability to provide informed consent for the&#xD;
             study/procedure, prevents independent lifestyle outside of a chronic care facility, or&#xD;
             will fundamentally complicate rehabilitation from the procedure or compliance with&#xD;
             follow-up visits).&#xD;
&#xD;
          -  Currently participating in an investigational drug or another device study.&#xD;
&#xD;
          -  Symptomatic carotid or vertebral artery disease.&#xD;
&#xD;
        Anatomical&#xD;
&#xD;
        Subject has a:&#xD;
&#xD;
          -  Native aortic annulus size &lt;18 mm or &gt;29 mm per the baseline diagnostic imaging (not&#xD;
             applicable for TAV in SAV subjects) OR&#xD;
&#xD;
          -  Surgical bioprosthetic annulus &lt;17mm or &gt;29mm i. Stented SAV per the manufactured&#xD;
             labeled inner diameter OR ii. Stentless SAV per the baseline diagnostic imaging&#xD;
&#xD;
          -  Subject has a pre-existing prosthetic heart valve with a rigid support structure in&#xD;
             either the mitral or pulmonic position:&#xD;
&#xD;
               1. that could affect the implantation or function of the study valve OR&#xD;
&#xD;
               2. the implantation of the study valve could affect the function of the pre-existing&#xD;
                  prosthetic heart valve&#xD;
&#xD;
          -  Moderate to severe mitral stenosis.&#xD;
&#xD;
          -  Mixed aortic valve disease: aortic stenosis and aortic regurgitation with predominant&#xD;
             aortic regurgitation, (AR is moderate-severe to severe (≥3-4+))(except for failed&#xD;
             surgical bioprothesis)&#xD;
&#xD;
          -  Hypertrophic obstructive cardiomyopathy.&#xD;
&#xD;
          -  Echocardiographic evidence of new or untreated intracardiac mass, thrombus or&#xD;
             vegetation.&#xD;
&#xD;
          -  Severe basal septal hypertrophy with an outflow gradient.&#xD;
&#xD;
          -  Aortic root angulation (angle between plane of aortic valve annulus and horizontal&#xD;
             plane/vertebrae) &gt;70° (for femoral and left subclavian/axillary access) and &gt;30° (for&#xD;
             right subclavian/axillary access).&#xD;
&#xD;
          -  Ascending aorta that exceeds the maximum diameter for any given native or surgical&#xD;
             bioprosthetic* aortic annulus size (see table below) Aortic Annulus Diameter/&#xD;
             Ascending Aorta Diameter, 18 mm* - 20 mm/ &gt;34 mm, 20 mm - 23 mm/ &gt;40 mm, 23 mm - 27&#xD;
             mm/ &gt;43 mm, 27 mm - 29 mm/ &gt;43 mm,&#xD;
&#xD;
             * 17mm for surgical bioprosthetic aortic annulus&#xD;
&#xD;
          -  Congenital bicuspid or unicuspid valve verified by echocardiography (Not applicable&#xD;
             for TAV in SAV subjects).&#xD;
&#xD;
          -  Sinus of valsalva anatomy that would prevent adequate coronary perfusion.&#xD;
&#xD;
          -  Degenerated surgical bioprothesis presents with a significant concomitant perivalvular&#xD;
             leak (between prothesis and native annulus), is not securely fixed in the native&#xD;
             annulus, or is not structurally intact (e.g. wireform frame fracture) (ONLY FOR TAV in&#xD;
             SAV subjects)&#xD;
&#xD;
          -  Degenerated surgical bioprothesis presents with a partially detached leaflet that in&#xD;
             the aortic position may obstruct a coronary ostium (ONLY FOR TAV in SAV subjects)&#xD;
&#xD;
        Vascular&#xD;
&#xD;
          -  Transarterial access not able to accommodate an 18Fr sheath.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David H Adams</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mount Sinai Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner Good Samaritan</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Los Angeles Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California University Hospital</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Palo Alto Health Care System</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale New Haven Hospital</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington Hospital Center / Georgetown Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Health System / Jackson Memorial Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Heart Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph's Hospital of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Heart Center of Indiana</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46290-1090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Heart Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Institute of the South/Terrebonne General</name>
      <address>
        <city>Houma</city>
        <state>Louisiana</state>
        <zip>70360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Health Systems</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Detroit Medical Center Cardiovascular Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. John Hospital and Medical Center</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health Hospitals</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Memorial Hospital</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Mount Sinai Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lenox Hill Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Hospital</name>
      <address>
        <city>Roslyn</city>
        <state>New York</state>
        <zip>11576</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University - Baptist Medical Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals - Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Medical Center - The Richard M. Ross Heart Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riverside Methodist Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pinnacle Health</name>
      <address>
        <city>Wormleysburg</city>
        <state>Pennsylvania</state>
        <zip>17101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Heart and Vascular Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Heart Institute at St. Luke's Episcopal Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Methodist Hospital - The Methodist DeBakey Heart &amp; Vascular Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Fairfax Hospital</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Medical Center - Aurora Health Care</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>April 28, 2023</last_update_submitted>
  <last_update_submitted_qc>April 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2023</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>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Constriction, Pathologic</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/NCT01675440
org study id: 10050361DOC
nct id: NCT01675440
lead sponsor: 
has dmc: Yes
To evaluate the safety and efficacy of the Medtronic CoreValve® System for the treatment of
      symptomatic severe aortic stenosis in subjects with significant comorbidities in whom the
      risk of surgical aortic valve replacement has a predicted operative mortality or serious,
      irreversible morbidity risk of ≥50% at 30 days.
The primary objective of the study is to evaluate the safety and effectiveness of the
      Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme Risk
      Pivotal Trial population due to one or more additional co-morbidities, as measured by a
      composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic
      severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled
      in this study have a predicted operative mortality or serious, irreversible morbidity risk of
      ≥50% at 30 days associated with surgical aortic valve replacement.
observational model: Cohort
time perspective: Prospective
measure: All-cause Mortality or Major stroke
time frame: 12 months
description: All-cause Mortality or Major Stroke
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) Event Rate
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: MACCE is defined as a composite of: • All-Cause Death • Myocardial Infarction (MI) • All Stroke • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
measure: The Occurrence of individual MACCE Components
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: Individual MACCE Components Include: - All Cause Mortality - MI - All stroke - Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
measure: Major Adverse Events (MAEs)
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: MAEs Include: •MACCE •Acute Kidney Injury •Cardiac Tamponade •Prosthetic Valve Dysfunction •Cardiogenic Shock •Valve Endocarditis •Life-Threatening, Disabling or Major Bleeding •Major Vascular Complication •Cardiac Perforation •Device Migration/Valve Embolism
measure: Conduction Disturbance Requiring Permanent Pacemaker Implantation
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: The incidence of conduction disturbance requiring permanent pacemaker implantation
measure: Change in NYHA Class
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.
measure: Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline
time frame: 30 days and 12 months
description: Change in distance walked during 6MWT from baseline
measure: Ratio of Days Alive Out of Hospital Versus Total Days Alive
time frame: 12 months
measure: Quality of Life (QoL) Change from Baseline
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: QoL change from baseline using the following measures: •Kansas City Cardiomyopathy Questionnaire (KCCQ) •SF-12 •EuroQoL
measure: Echocardiographic Assessment of Valve Performance
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: Using the following measures: • Transvalvular mean gradient • Effective orifice area (EOA) •degree of aortic valve regurgitation
measure: Aortic Valve Disease Hospitalization
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: The number of subjects re-hospitalized after the initial procedure
measure: Cardiovascular Deaths and Valve-related Deaths
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: The number of cardiovascular deaths and valve-related deaths
measure: Strokes
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: The number of subjects with strokes and TIAs
measure: Index Procedure Related Major Adverse Events (MAEs)
time frame: Procedure
description: Index procedure-related MAE events will be summarized
measure: Length of Index Procedure Hospital Stay
time frame: Number of days from admission to discharge
description: The length of index procedure hospital stay will be summarized
measure: Device Success
time frame: Number of days from admission to discharge
description: Defined as: 1) Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system, 2) Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function), 3) Intended performance of the prosthetic valve (aortic valve area > 1.2 cm2 for 26, 29 and 31mm valves, ≥ 0.9 cm2 for 23mm valve (by echocardiography using the continuity equation) and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/sec, without moderate or severe prosthetic valve aortic regurgitation) 4) Only one valve implanted in the proper anatomical location. For TAV in SAV subjects, only # 1, 2 and 4 will be used to calculate device success.
measure: Procedural Success
time frame: Number of days from admission to discharge
description: Defined as device success and absence of in-hospital MACCE
measure: Evidence of Prosthetic Valve Dysfunction
time frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
description: PVD was defined according to VARC using the site reported echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met: •Peak velocity > 4 m/s •Mean gradient > 35 mmHg •EOA < 0.8 cm2 •TVIV1 / TVIV2 < 0.25
arm group label: Severe (≥3-4+) Mitral Valve Regurgitation
description: Mitral valve regurgitation ≥3-4+
arm group label: Severe (≥3-4+) Tricuspid Valve Regurgitation
description: Tricuspid valve regurgitation ≥3-4+
arm group label: End Stage Renal Disease (ESRD)
description: End stage renal disease requiring renal replacement therapy or a creatinine clearance (CRCL) <20 cc/min, but not on dialysis
arm group label: Low Gradient Low Output Aortic Stenosis
description: Low gradient low output aortic stenosis
arm group label: Failed Bioprosthetic Surgical Aortic Valve
description: Stenosed, insufficient or combined bioprosthetic surgical aortic valve failure
arm group label: 2 or More Conditions
description: 2 or more of the listed conditions
intervention type: Device
intervention name: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
arm group label: 2 or More Conditions
arm group label: End Stage Renal Disease (ESRD)
arm group label: Failed Bioprosthetic Surgical Aortic Valve
arm group label: Low Gradient Low Output Aortic Stenosis
arm group label: Severe (≥3-4+) Mitral Valve Regurgitation
arm group label: Severe (≥3-4+) Tricuspid Valve Regurgitation
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: David H Adams
role: Principal Investigator
affiliation: Mount Sinai Health System
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country: United States
responsible party type: Sponsor
mesh term: Aortic Valve Stenosis
mesh term: Constriction, Pathologic