<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/NCT04408430</url>
  </required_header>
  <id_info>
    <org_study_id>20-002438</org_study_id>
    <nct_id>NCT04408430</nct_id>
  </id_info>
  <brief_title>The MITRAL II Pivotal Trial (Mitral Implantation of TRAnscatheter vaLves).</brief_title>
  <acronym>MITRAL-II</acronym>
  <official_title>The Safety and Effectiveness of the SAPIEN 3 and SAPIEN 3 Ultra Valve in Patients With Symptomatic Severe Calcific Mitral Valve Disease With Severe Mitral Annular Calcification Who Are Not Candidates for Standard Mitral Valve Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayra Guerrero</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective multicenter study enrolling high surgical risk patients with severe mitral&#xD;
      annular calcification (MAC) and symptomatic mitral valve disease. There are 2 arms in this&#xD;
      study: Transseptal Valve-in-MAC (ViMAC) and a control arm of patients treated with medical&#xD;
      treatment only which will include patients who can't be treated due to the presence of&#xD;
      anatomical exclusion criteria or other exclusion criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY OBJECTIVE&#xD;
&#xD;
      The purpose of this study is to establish the safety and effectiveness of the Edwards SAPIEN&#xD;
      3 and SAPIEN 3 Ultra valves with Commander delivery system in patients with severe&#xD;
      symptomatic calcific mitral valve disease with severe mitral annular calcification who are&#xD;
      not candidates for standard mitral valve surgery.&#xD;
&#xD;
      STUDY DESIGN&#xD;
&#xD;
      A prospective multicenter study enrolling high surgical risk patients with severe mitral&#xD;
      annular calcification (MAC) and symptomatic mitral valve disease. There are 2 arms in this&#xD;
      study: Transseptal Valve-in-MAC (ViMAC) and a control arm of patients treated with medical&#xD;
      treatment only which will include patients who can't be treated due to the presence of&#xD;
      anatomical exclusion criteria or other exclusion criteria.&#xD;
&#xD;
      Enrollment Enrollment will consist of 110 patients in the treatment arm (transseptal ViMAC)&#xD;
      and up to 100 in the medically treated arm).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 8, 2021</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>210 subjects: 110 in treatment arm and 100 in registry of medical treatment for patients who are not eligible for treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Safety Endpoint: All Cause Morality and Hospitalization for Heart Failure</measure>
    <time_frame>1 year.</time_frame>
    <description>A non-hierarchical composite of all-cause mortality and hospitalization for heart failure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness Endpoint</measure>
    <time_frame>1 year</time_frame>
    <description>• Stroke at 30 days and 1 year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness Endpoint</measure>
    <time_frame>1 year.</time_frame>
    <description>• Change from baseline in New York Heart Association Class at 1 year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness Endpoint</measure>
    <time_frame>1 year.</time_frame>
    <description>• Change from baseline in distance walked measure by the 6 Minute Walk Test at 1 year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness Endpoint</measure>
    <time_frame>1 year.</time_frame>
    <description>• Change from baseline in quality of life measure by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 1 year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness Endpoint</measure>
    <time_frame>1 year.</time_frame>
    <description>• Echocardiographic assessment of degree of mitral regurgitation (central and paravalvular) at 1 year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness Endpoint</measure>
    <time_frame>1 year.</time_frame>
    <description>• Significant mitral stenosis defined as mean mitral valve gradient by echo &gt; 10 mmHg at 1 year.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Additional Endpoint: Technical Success</measure>
    <time_frame>Immediately after the intervention procedure.</time_frame>
    <description>• Technical success at exit from the cath lab.&#xD;
Defined as:&#xD;
Successful vascular access, delivery and retrieval of the transcatheter valve delivery system.&#xD;
Deployment of a single valve.&#xD;
Correct position of transcatheter valve in the mitral annulus.&#xD;
Adequate performance of the prosthetic heart valve (MVA &gt; 1.5 cm2) without residual mitral regurgitation grade ≥2 (+).&#xD;
No need for additional surgery or re-intervention (includes drainage of pericardial effusion).&#xD;
The patient leaves the cath lab alive.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Endpoint: Procedural Success</measure>
    <time_frame>30 days</time_frame>
    <description>• Procedural Success at 30 days.&#xD;
Defined as:&#xD;
Device success at 30 days.&#xD;
No device/procedure related SAE's including: death, stroke, MI or coronary ischemia requiring PCI or CABG, stage 2 or 3 AKI including dialysis, life threatening bleeding, major vascular or access complications (arterial, venous, or TA - any event requiring additional unplanned surgical or transcatheter intervention), pericardial effusion or tamponade requiring drainage, severe hypotension, heart failure or respiratory failure requiring intravenous pressors or invasive or mechanical treatments such as ultrafiltration or hemodynamic assist devices including intra-aortic balloon pump or left ventricular assist device, or prolonged intubation for ≥48 hrs, or any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Endpoint: Device Success</measure>
    <time_frame>30 days.</time_frame>
    <description>Device success is defined as:&#xD;
Stroke free survival with original valve in place.&#xD;
No need for additional surgery or re-intervention related to the procedure, access or to the replacement valve.&#xD;
Proper placement and intended function of the replacement valve, including&#xD;
No migration, fracture, thrombosis, hemolysis or endocarditis.&#xD;
No replacement valve stenosis (MV gradient &lt; 10 mmHg).&#xD;
Replacement valve regurgitation &lt; 2 + (including central and paravalvular leak) and without associated hemolysis.&#xD;
No increase in AI from baseline (more than 1 grade) and LVOT gradient &lt; 20 mmHg increase from baseline.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Efficacy Endpoint - NYHA Class at 30 days.</measure>
    <time_frame>30 days.</time_frame>
    <description>• Change from baseline in NYHA Class at 30 days.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Efficacy Endpoint - Distance walked in 6 MWT at 30 days</measure>
    <time_frame>30 days.</time_frame>
    <description>• Change from baseline in distance walked measure by the 6 MWT at 30 days.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Efficacy Endpoint - KCCQ at 30 days</measure>
    <time_frame>30 days.</time_frame>
    <description>• Change from baseline in KCCQ at 30 days.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Efficacy Endpoint - MR severity at 30 days</measure>
    <time_frame>30 days</time_frame>
    <description>• Degree of mitral regurgitation (central and paravalvular) at 30 days.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Stroke at 30 days and 1 year.</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• Stroke at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Need for ASD Closure</measure>
    <time_frame>30 days.</time_frame>
    <description>• Iatrogenic ASD causing RV failure or hypoxemia or need for ASD closure at discharge and 30 days.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - New LVOT Gradient</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• New mean LVOT gradient ≥ 20 mmHg, or ≥ 20 mmHg increase from baseline LVOT gradient at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Efficacy Endpoint - Mitral Valve Reintervention</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• Mitral Valve reintervention at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Hospitalizations at 1 year</measure>
    <time_frame>1 year.</time_frame>
    <description>• Number of hospitalizations at 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Efficacy Endpoint - Days Alive Out of the Hospital</measure>
    <time_frame>1 year.</time_frame>
    <description>• Days alive out of hospital at 1 year from index procedure (ViMAC arm) or from enrollment day (medical treatment arm).</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Hemolysis</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• Hemolysis at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Endocarditis</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• Endocarditis at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Blood Transfusion</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• Blood transfusion at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - New Pacemaker Requirement</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• New pacemaker requirement at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - New Aortic Valve Insufficiency</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• New aortic valve insufficiency at 30 days and 1 year.</description>
  </other_outcome>
  <other_outcome>
    <measure>Additional Safety Endpoint - Acute Kidney Injury</measure>
    <time_frame>30 days and 1 year.</time_frame>
    <description>• Acute kidney injury (MVARC) at 30 days and 1 year.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Mitral Annular Calcification</condition>
  <condition>Mitral Stenosis</condition>
  <condition>Mitral Regurgitation</condition>
  <condition>Mitral Valve Disease</condition>
  <arm_group>
    <arm_group_label>Transseptal ViMAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>110 MAC patients treated with transseptal Valve-in-MAC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Registry of untreated patients</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>100 MAC patients not eligible for transseptal ViMAC, treated with conservative management including medications.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transseptal ViMAC</intervention_name>
    <description>Transseptal TMVR using balloon-expandable aortic transcatheter valves.</description>
    <arm_group_label>Transseptal ViMAC</arm_group_label>
    <other_name>ViMAC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All Candidates must meet the following criteria:&#xD;
&#xD;
          1. - 18 years of age or older&#xD;
&#xD;
          2. -Severe mitral annular calcification with severe mitral stenosis defined as mitral&#xD;
             valve area (MVA) of ≤1.5 cm2, or moderate to severe or severe mitral regurgitation.&#xD;
&#xD;
          3. - NYHA Functional Class ≥II.&#xD;
&#xD;
          4. The heart team agrees that valve implantation will likely benefit the patient.&#xD;
&#xD;
          5. High or prohibitive risk for standard mitral valve surgery as determined by the heart&#xD;
             team (at least one site cardiac surgeon must personally examine the subject to&#xD;
             determine operative risk).&#xD;
&#xD;
          6. The study patient has been informed of the nature of the study, agrees to its&#xD;
             provisions and has provided written informed consent as approved by the Institutional&#xD;
             Review Board (IRB) of the respective clinical site.&#xD;
&#xD;
          7. The study patient agrees to comply with all required post-procedure follow-up visits&#xD;
             including annual visits through 5 years and analysis close date visits, which will be&#xD;
             conducted as a phone follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. - The heart team considers the patient is a surgical candidate.&#xD;
&#xD;
          2. - Mitral annulus is not calcified.&#xD;
&#xD;
          3. - Myocardial infarction requiring revascularization within 30 days from procedure.&#xD;
&#xD;
          4. - Clinically significant untreated coronary artery disease requiring&#xD;
             revascularization.&#xD;
&#xD;
          5. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is&#xD;
             performed within 30 days of the index procedure (unless part of planned strategy for&#xD;
             treatment of concomitant coronary artery disease). Implantation of a permanent&#xD;
             pacemaker is not excluded.&#xD;
&#xD;
          6. Any patient with a balloon valvuloplasty (BMV) within 30 days of the procedure (unless&#xD;
             BMV is a bridge to procedure after a qualifying Echo).&#xD;
&#xD;
          7. Severe symptomatic tricuspid regurgitation (hepatic dysfunction, ascites, edema not&#xD;
             controlled with diuretics) requiring surgery.&#xD;
&#xD;
          8. Leukopenia (WBC &lt; 3000 cell/mL), acute anemia (Hgb &lt; 9 g/dL), Thrombocytopenia&#xD;
             (Platelets &lt; 50,000 cell/mL), history of coagulopathy or hypercoagulable state.&#xD;
&#xD;
          9. Hypertrophic obstructive cardiomyopathy (HOCM) with mean LVOT gradient of ≥20 mm Hg at&#xD;
             rest or ≥50 mmHg with Valsalva.&#xD;
&#xD;
         10. Hemodynamic or respiratory instability requiring inotropic support, mechanical&#xD;
             ventilation or mechanical heart assistance within 30 days of screening evaluation.&#xD;
&#xD;
         11. Need for emergency surgery for any reason.&#xD;
&#xD;
         12. Severe left ventricular dysfunction with LVEF &lt; 20%.&#xD;
&#xD;
         13. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.&#xD;
&#xD;
         14. Active upper GI bleeding within 90 days prior to procedure.&#xD;
&#xD;
         15. A known contraindication or hypersensitivity to all anticoagulation regimens, or&#xD;
             inability to be anticoagulated for the study procedure.&#xD;
&#xD;
         16. Cardiac anatomy that would preclude appropriate delivery and deployment of a SAPIEN 3&#xD;
             or SAPIEN 3 Ultra valve in MAC via transseptal access, including but not limited to:&#xD;
&#xD;
               -  Native neo mitral annulus size &lt; 275 mm2 or &gt; 810 mm2 as measured by CT scan.&#xD;
&#xD;
               -  Significant risk of LVOT obstruction or valve embolization as assessed by CT core&#xD;
                  lab&#xD;
&#xD;
         17. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic&#xD;
             attack (TIA) within 90 days of the procedure.&#xD;
&#xD;
         18. Estimated life expectancy &lt;12 months due to non-cardiac conditions.&#xD;
&#xD;
         19. Expectation that patient will not improve despite treatment of mitral valve&#xD;
             dysfunction.&#xD;
&#xD;
         20. Active bacterial endocarditis within 180 days of procedure.&#xD;
&#xD;
         21. - Severe right ventricular dysfunction as assessed by Echo core lab&#xD;
&#xD;
         22. - Active infection requiring antibiotic therapy (subject may be a candidate after 2&#xD;
             weeks of antibiotic discontinuation.&#xD;
&#xD;
         23. - Female who is pregnant or lactating.&#xD;
&#xD;
         24. - Participating in another investigational device study.&#xD;
&#xD;
         25. - Aortic valve disease requiring intervention.&#xD;
&#xD;
         26. - Severe fixed pulmonary hypertension (PASP ≥70 mmHg).&#xD;
&#xD;
         27. - Severe chronic obstructive pulmonary disease requiring continuous home oxygen.&#xD;
&#xD;
         28. - The patient refuses mitral valve intervention&#xD;
&#xD;
         29. - Recent symptomatic COVID-19 infection with residual symptoms that may affect the&#xD;
             outcomes of this trial.&#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>Mayra Guerrero, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tatiana Kaptzan, Ph. D.</last_name>
    <phone>507-284-1610</phone>
    <email>kaptzan.tatiana@mayo.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Banner - University Medicine Cardiology Clinic</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Marvin Eng, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Pima Heart &amp; Vascular</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Thomas E Waggoner, DO</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sutter Health</name>
      <address>
        <city>Burlingame</city>
        <state>California</state>
        <zip>94010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Milena Ferreira</last_name>
      <phone>415-600-5707</phone>
      <email>ferreiml@sutterhealth.org</email>
    </contact>
    <contact_backup>
      <last_name>Andrea Davila</last_name>
      <email>Davilaa2@sutterhealth.org</email>
    </contact_backup>
    <investigator>
      <last_name>David Daniels, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Raj Makkar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Uchealth Heart &amp; Vascular Clinic Harmony Campus</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80528</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Bradley Oldemeyer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Medstar Washington Hospital Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>200100</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Lowell Satler, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Piedmont Healthcare</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Pradeep Kumar Yadav, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northwestern University Medical School</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Chris Malaisrie, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ignacio Inglessis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pinak Shah, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Roger Laham, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>William O'Neill, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Craig Konwinski</last_name>
      <phone>507-255-9525</phone>
      <email>Konwinski.craig@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Mackram Eleid, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center/NYPH</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Treena Willimas</last_name>
      <email>taw2112@cumc.columbia.edu</email>
    </contact>
    <investigator>
      <last_name>Susheel Kodali, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oklahoma Heart Institute Utica Office</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Kamran I Muhammad, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Firars Zahr, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White - The Heart Hospital - Plano</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75093</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Molly Szerlip, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brenda Carroll</last_name>
      <email>Brenda.Carroll@imail.org</email>
    </contact>
    <investigator>
      <last_name>Brian Whisenant, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Sentara Heart Valve and Structural Disease Center</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tina Calayo</last_name>
      <email>CACALAYO@sentara.com</email>
    </contact>
    <investigator>
      <last_name>Paul Mahoney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <reference>
    <citation>Russell HM, Guerrero ME, Salinger MH, Manzuk MA, Pursnani AK, Wang D, Nemeh H, Sakhuja R, Melnitchouk S, Pershad A, Fang HK, Said SM, Kauten J, Tang GHL, Aldea G, Feldman TE, Bapat VN, George IM. Open Atrial Transcatheter Mitral Valve Replacement in Patients With Mitral Annular Calcification. J Am Coll Cardiol. 2018 Sep 25;72(13):1437-1448. doi: 10.1016/j.jacc.2018.07.033.</citation>
    <PMID>30236304</PMID>
  </reference>
  <reference>
    <citation>Guerrero M, Wang DD, Himbert D, Urena M, Pursnani A, Kaddissi G, Iyer V, Salinger M, Chakravarty T, Greenbaum A, Makkar R, Vahanian A, Feldman T, O'Neill W. Short-term results of alcohol septal ablation as a bail-out strategy to treat severe left ventricular outflow tract obstruction after transcatheter mitral valve replacement in patients with severe mitral annular calcification. Catheter Cardiovasc Interv. 2017 Dec 1;90(7):1220-1226. doi: 10.1002/ccd.26975. Epub 2017 Mar 7.</citation>
    <PMID>28266162</PMID>
  </reference>
  <reference>
    <citation>Guerrero M, Wang DD, O'Neill W. Percutaneous alcohol septal ablation to acutely reduce left ventricular outflow tract obstruction induced by transcatheter mitral valve replacement. Catheter Cardiovasc Interv. 2016 Nov 15;88(6):E191-E197. doi: 10.1002/ccd.26649. Epub 2016 Jul 5.</citation>
    <PMID>27377756</PMID>
  </reference>
  <reference>
    <citation>Guerrero M, Urena M, Pursnani A, Wang DD, Vahanian A, O'Neill W, Feldman T, Himbert D. Balloon expandable transcatheter heart valves for native mitral valve disease with severe mitral annular calcification. J Cardiovasc Surg (Torino). 2016 Jun;57(3):401-9.</citation>
    <PMID>27094423</PMID>
  </reference>
  <reference>
    <citation>Guerrero M, Greenbaum A, O'Neill W. First in human percutaneous implantation of a balloon expandable transcatheter heart valve in a severely stenosed native mitral valve. Catheter Cardiovasc Interv. 2014 Jun 1;83(7):E287-91. doi: 10.1002/ccd.25441. Epub 2014 Mar 14.</citation>
    <PMID>24532349</PMID>
  </reference>
  <results_reference>
    <citation>Guerrero M, Urena M, Himbert D, Wang DD, Eleid M, Kodali S, George I, Chakravarty T, Mathur M, Holzhey D, Pershad A, Fang HK, O'Hair D, Jones N, Mahadevan VS, Dumonteil N, Rodes-Cabau J, Piazza N, Ferrari E, Ciaburri D, Nejjari M, DeLago A, Sorajja P, Zahr F, Rajagopal V, Whisenant B, Shah PB, Sinning JM, Witkowski A, Eltchaninoff H, Dvir D, Martin B, Attizzani GF, Gaia D, Nunes NSV, Fassa AA, Kerendi F, Pavlides G, Iyer V, Kaddissi G, Witzke C, Wudel J, Mishkel G, Raybuck B, Wang C, Waksman R, Palacios I, Cribier A, Webb J, Bapat V, Reisman M, Makkar R, Leon M, Rihal C, Vahanian A, O'Neill W, Feldman T. 1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification. J Am Coll Cardiol. 2018 May 1;71(17):1841-1853. doi: 10.1016/j.jacc.2018.02.054.</citation>
    <PMID>29699609</PMID>
  </results_reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>March 27, 2023</last_update_submitted>
  <last_update_submitted_qc>March 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Mayra Guerrero</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Transcatheter Mitral Valve Replacement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitral Valve Insufficiency</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
    <mesh_term>Mitral Valve Stenosis</mesh_term>
    <mesh_term>Calcinosis</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/NCT04408430
org study id: 20-002438
nct id: NCT04408430
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
A prospective multicenter study enrolling high surgical risk patients with severe mitral
      annular calcification (MAC) and symptomatic mitral valve disease. There are 2 arms in this
      study: Transseptal Valve-in-MAC (ViMAC) and a control arm of patients treated with medical
      treatment only which will include patients who can't be treated due to the presence of
      anatomical exclusion criteria or other exclusion criteria.
STUDY OBJECTIVE

      The purpose of this study is to establish the safety and effectiveness of the Edwards SAPIEN
      3 and SAPIEN 3 Ultra valves with Commander delivery system in patients with severe
      symptomatic calcific mitral valve disease with severe mitral annular calcification who are
      not candidates for standard mitral valve surgery.

      STUDY DESIGN

      A prospective multicenter study enrolling high surgical risk patients with severe mitral
      annular calcification (MAC) and symptomatic mitral valve disease. There are 2 arms in this
      study: Transseptal Valve-in-MAC (ViMAC) and a control arm of patients treated with medical
      treatment only which will include patients who can't be treated due to the presence of
      anatomical exclusion criteria or other exclusion criteria.

      Enrollment Enrollment will consist of 110 patients in the treatment arm (transseptal ViMAC)
      and up to 100 in the medically treated arm).
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: 210 subjects: 110 in treatment arm and 100 in registry of medical treatment for patients who are not eligible for treatment.
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Safety Endpoint: All Cause Morality and Hospitalization for Heart Failure
time frame: 1 year.
description: A non-hierarchical composite of all-cause mortality and hospitalization for heart failure.
measure: Secondary Effectiveness Endpoint
time frame: 1 year
description: • Stroke at 30 days and 1 year.
measure: Secondary Effectiveness Endpoint
time frame: 1 year.
description: • Change from baseline in New York Heart Association Class at 1 year.
measure: Secondary Effectiveness Endpoint
time frame: 1 year.
description: • Change from baseline in distance walked measure by the 6 Minute Walk Test at 1 year.
measure: Secondary Effectiveness Endpoint
time frame: 1 year.
description: • Change from baseline in quality of life measure by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 1 year.
measure: Secondary Effectiveness Endpoint
time frame: 1 year.
description: • Echocardiographic assessment of degree of mitral regurgitation (central and paravalvular) at 1 year.
measure: Secondary Effectiveness Endpoint
time frame: 1 year.
description: • Significant mitral stenosis defined as mean mitral valve gradient by echo > 10 mmHg at 1 year.
measure: Additional Endpoint: Technical Success
time frame: Immediately after the intervention procedure.
description: • Technical success at exit from the cath lab.
Defined as:
Successful vascular access, delivery and retrieval of the transcatheter valve delivery system.
Deployment of a single valve.
Correct position of transcatheter valve in the mitral annulus.
Adequate performance of the prosthetic heart valve (MVA > 1.5 cm2) without residual mitral regurgitation grade ≥2 (+).
No need for additional surgery or re-intervention (includes drainage of pericardial effusion).
The patient leaves the cath lab alive.
measure: Additional Endpoint: Procedural Success
time frame: 30 days
description: • Procedural Success at 30 days.
Defined as:
Device success at 30 days.
No device/procedure related SAE's including: death, stroke, MI or coronary ischemia requiring PCI or CABG, stage 2 or 3 AKI including dialysis, life threatening bleeding, major vascular or access complications (arterial, venous, or TA - any event requiring additional unplanned surgical or transcatheter intervention), pericardial effusion or tamponade requiring drainage, severe hypotension, heart failure or respiratory failure requiring intravenous pressors or invasive or mechanical treatments such as ultrafiltration or hemodynamic assist devices including intra-aortic balloon pump or left ventricular assist device, or prolonged intubation for ≥48 hrs, or any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention.
measure: Additional Endpoint: Device Success
time frame: 30 days.
description: Device success is defined as:
Stroke free survival with original valve in place.
No need for additional surgery or re-intervention related to the procedure, access or to the replacement valve.
Proper placement and intended function of the replacement valve, including
No migration, fracture, thrombosis, hemolysis or endocarditis.
No replacement valve stenosis (MV gradient < 10 mmHg).
Replacement valve regurgitation < 2 + (including central and paravalvular leak) and without associated hemolysis.
No increase in AI from baseline (more than 1 grade) and LVOT gradient < 20 mmHg increase from baseline.
measure: Additional Efficacy Endpoint - NYHA Class at 30 days.
time frame: 30 days.
description: • Change from baseline in NYHA Class at 30 days.
measure: Additional Efficacy Endpoint - Distance walked in 6 MWT at 30 days
time frame: 30 days.
description: • Change from baseline in distance walked measure by the 6 MWT at 30 days.
measure: Additional Efficacy Endpoint - KCCQ at 30 days
time frame: 30 days.
description: • Change from baseline in KCCQ at 30 days.
measure: Additional Efficacy Endpoint - MR severity at 30 days
time frame: 30 days
description: • Degree of mitral regurgitation (central and paravalvular) at 30 days.
measure: Additional Safety Endpoint - Stroke at 30 days and 1 year.
time frame: 30 days and 1 year.
description: • Stroke at 30 days and 1 year.
measure: Additional Safety Endpoint - Need for ASD Closure
time frame: 30 days.
description: • Iatrogenic ASD causing RV failure or hypoxemia or need for ASD closure at discharge and 30 days.
measure: Additional Safety Endpoint - New LVOT Gradient
time frame: 30 days and 1 year.
description: • New mean LVOT gradient ≥ 20 mmHg, or ≥ 20 mmHg increase from baseline LVOT gradient at 30 days and 1 year.
measure: Additional Efficacy Endpoint - Mitral Valve Reintervention
time frame: 30 days and 1 year.
description: • Mitral Valve reintervention at 30 days and 1 year.
measure: Additional Safety Endpoint - Hospitalizations at 1 year
time frame: 1 year.
description: • Number of hospitalizations at 1 year.
measure: Additional Efficacy Endpoint - Days Alive Out of the Hospital
time frame: 1 year.
description: • Days alive out of hospital at 1 year from index procedure (ViMAC arm) or from enrollment day (medical treatment arm).
measure: Additional Safety Endpoint - Hemolysis
time frame: 30 days and 1 year.
description: • Hemolysis at 30 days and 1 year.
measure: Additional Safety Endpoint - Endocarditis
time frame: 30 days and 1 year.
description: • Endocarditis at 30 days and 1 year.
measure: Additional Safety Endpoint - Blood Transfusion
time frame: 30 days and 1 year.
description: • Blood transfusion at 30 days and 1 year.
measure: Additional Safety Endpoint - New Pacemaker Requirement
time frame: 30 days and 1 year.
description: • New pacemaker requirement at 30 days and 1 year.
measure: Additional Safety Endpoint - New Aortic Valve Insufficiency
time frame: 30 days and 1 year.
description: • New aortic valve insufficiency at 30 days and 1 year.
measure: Additional Safety Endpoint - Acute Kidney Injury
time frame: 30 days and 1 year.
description: • Acute kidney injury (MVARC) at 30 days and 1 year.
arm group label: Transseptal ViMAC
arm group type: Experimental
description: 110 MAC patients treated with transseptal Valve-in-MAC.
arm group label: Registry of untreated patients
arm group type: No Intervention
description: 100 MAC patients not eligible for transseptal ViMAC, treated with conservative management including medications.
intervention type: Device
intervention name: Transseptal ViMAC
description: Transseptal TMVR using balloon-expandable aortic transcatheter valves.
arm group label: Transseptal ViMAC
other name: ViMAC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mayra Guerrero, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Tatiana Kaptzan, Ph. D.
phone: 507-284-1610
email: kaptzan.tatiana@mayo.edu
facility: 
status: Not yet recruiting
investigator: 
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status: Not yet recruiting
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facility: 
status: Recruiting
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status: Not yet recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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contact: 
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country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
citation: Russell HM, Guerrero ME, Salinger MH, Manzuk MA, Pursnani AK, Wang D, Nemeh H, Sakhuja R, Melnitchouk S, Pershad A, Fang HK, Said SM, Kauten J, Tang GHL, Aldea G, Feldman TE, Bapat VN, George IM. Open Atrial Transcatheter Mitral Valve Replacement in Patients With Mitral Annular Calcification. J Am Coll Cardiol. 2018 Sep 25;72(13):1437-1448. doi: 10.1016/j.jacc.2018.07.033.
PMID: 30236304
citation: Guerrero M, Wang DD, Himbert D, Urena M, Pursnani A, Kaddissi G, Iyer V, Salinger M, Chakravarty T, Greenbaum A, Makkar R, Vahanian A, Feldman T, O'Neill W. Short-term results of alcohol septal ablation as a bail-out strategy to treat severe left ventricular outflow tract obstruction after transcatheter mitral valve replacement in patients with severe mitral annular calcification. Catheter Cardiovasc Interv. 2017 Dec 1;90(7):1220-1226. doi: 10.1002/ccd.26975. Epub 2017 Mar 7.
PMID: 28266162
citation: Guerrero M, Wang DD, O'Neill W. Percutaneous alcohol septal ablation to acutely reduce left ventricular outflow tract obstruction induced by transcatheter mitral valve replacement. Catheter Cardiovasc Interv. 2016 Nov 15;88(6):E191-E197. doi: 10.1002/ccd.26649. Epub 2016 Jul 5.
PMID: 27377756
citation: Guerrero M, Urena M, Pursnani A, Wang DD, Vahanian A, O'Neill W, Feldman T, Himbert D. Balloon expandable transcatheter heart valves for native mitral valve disease with severe mitral annular calcification. J Cardiovasc Surg (Torino). 2016 Jun;57(3):401-9.
PMID: 27094423
citation: Guerrero M, Greenbaum A, O'Neill W. First in human percutaneous implantation of a balloon expandable transcatheter heart valve in a severely stenosed native mitral valve. Catheter Cardiovasc Interv. 2014 Jun 1;83(7):E287-91. doi: 10.1002/ccd.25441. Epub 2014 Mar 14.
PMID: 24532349
citation: Guerrero M, Urena M, Himbert D, Wang DD, Eleid M, Kodali S, George I, Chakravarty T, Mathur M, Holzhey D, Pershad A, Fang HK, O'Hair D, Jones N, Mahadevan VS, Dumonteil N, Rodes-Cabau J, Piazza N, Ferrari E, Ciaburri D, Nejjari M, DeLago A, Sorajja P, Zahr F, Rajagopal V, Whisenant B, Shah PB, Sinning JM, Witkowski A, Eltchaninoff H, Dvir D, Martin B, Attizzani GF, Gaia D, Nunes NSV, Fassa AA, Kerendi F, Pavlides G, Iyer V, Kaddissi G, Witzke C, Wudel J, Mishkel G, Raybuck B, Wang C, Waksman R, Palacios I, Cribier A, Webb J, Bapat V, Reisman M, Makkar R, Leon M, Rihal C, Vahanian A, O'Neill W, Feldman T. 1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification. J Am Coll Cardiol. 2018 May 1;71(17):1841-1853. doi: 10.1016/j.jacc.2018.02.054.
PMID: 29699609
responsible party type: Sponsor-Investigator
investigator affiliation: Mayo Clinic
investigator full name: Mayra Guerrero
investigator title: Principal Investigator
mesh term: Mitral Valve Insufficiency
mesh term: Heart Valve Diseases
mesh term: Mitral Valve Stenosis
mesh term: Calcinosis
sharing ipd: No