Medtronic CoreValve Evolut R U.S. Clinical Study (Evolut 34R Addendum)

Medtronic CoreValve Evolut R United States Clinical Study (Evolut 34R Addendum)

The study objectives are to assess the safety and efficacy of the CoreValve Evolut 34R transcatheter aortic valve replacement (TAVR) system in patients with severe symptomatic aortic stenosis who are considered at high or extreme risk for surgical aortic valve replacement.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: CoreValve Evolut 34R TAVR system

Detailed Description

This objective will be accomplished by a prospective, single arm, historical controlled, multi-site study involving up to 60 implanted subjects at up to 15 study sites in the United States. Procedural and 30 day safety and efficacy results from this study will be compared to appropriate historical control data for the Medtronic CoreValve System. Subjects will be followed up to 5 years following implantation.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale New Haven Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Systems
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospitals
  • New York
    • New York, New York, United States, 10016
      • New York Langone Medical Center
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17104
      • Pinnacle Health/Moffitt Heart and Vascular Institute
  • Texas
    • Dallas, Texas, United States, 75225
      • Baylor Heart and Vascular Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care/St Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Severe aortic stenosis, defined as aortic valve area of < 1.0 cm2 (or aortic valve area index of < 0.6 cm2/m2) by the continuity equation, AND mean gradient > 40 mmHg or maximal aortic valve velocity > 4.0 m/sec by resting echocardiogram.

   Subjects with low-flow/low gradient severe aortic stenosis can be included, provided low-dose dobutamine or exercise stress echocardiography demonstrates a mean gradient of > 40 mmHg or a maximal aortic valve velocity of > 4.0 m/sec, AND aortic valve area of < 1.0 cm2 (or aortic valve area index of < 0.6 cm2/m2).

2. Society of Thoracic Surgeons (STS) score of ≥ 8 OR documented heart team agreement of ≥ high risk for aortic valve replacement due to frailty or co-morbidities.
3. Symptoms of aortic stenosis, AND New York Heart Association (NYHA) Functional Class II or greater.

4. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

   Exclusion Criteria:

5. Any condition considered a contraindication for placement of a bioprosthetic valve (e.g. subject is indicated for mechanical prosthetic valve).

6. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

   • aspirin or heparin (HIT/HITTS) and bivalirudin
   • ticlopidine and clopidogrel
   • Nitinol (titanium or nickel)
   • contrast media
7. Blood dyscrasias as defined: leukopenia (WBC < 1000 mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
8. Untreated clinically significant coronary artery disease requiring revascularization.
9. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% by echocardiography, contrast ventriculography, or radionuclide ventriculography.
10. End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min.
11. Ongoing sepsis, including active endocarditis.
12. Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug eluting stent performed within 30 days prior to study procedure.
13. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.
14. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
15. Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
16. Gastrointestinal (GI) bleeding that would preclude anticoagulation.
17. Subject refuses a blood transfusion.
18. Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
19. Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid conditions.
20. Other medical, social, or psychological conditions that in the opinion of the investigator precludes the subject from appropriate consent or adherence to the protocol required follow-ups exams.
21. Currently participating in an investigational drug or another device study (excluding registries).
22. Evidence of an acute myocardial infarction ≤ 30 days before the study procedure.
23. Need for emergency surgery for any reason.
24. Liver failure (Child-Pugh class C).

25. Subject is pregnant or breast feeding.

    Anatomical exclusion criteria:

26. Pre-existing prosthetic heart valve in any position.
27. Mixed aortic valve disease (aortic stenosis with severe aortic regurgitation).
28. Severe mitral regurgitation.
29. Severe tricuspid regurgitation.
30. Moderate or severe mitral stenosis.
31. Hypertrophic obstructive cardiomyopathy.
32. Echocardiographic or Multi-Slice Computed Tomography (MSCT) evidence of intracardiac mass, thrombus, or vegetation.

33. Congenital bicuspid or unicuspid valve verified by echocardiography.

    For transfemoral or transaxillary (subclavian) access:

34. Access vessel diameter < 5.5 mm or <6.0 mm for patent left internal mammary artery (LIMA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CoreValve Evolut 34R TAVR system; Treatment of Aortic Stenosis with Medtronic CoreValve Evolut R 34R TAVR System.	Device: CoreValve Evolut 34R TAVR system; The CoreValve Evolut 34R System is a transcatheter aortic valve implantation system comprised of the following three components: Evolut 34R Transcatheter Aortic Valve (TAV); EnVeo R Delivery Catheter System (DCS) with EnVeo R InLine Sheath; EnVeo R Loading System (LS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With All-cause Mortality	Percentage of participants with all-cause mortality at 30 days	30 Days
Percentage of Participants With Stroke (Disabling)	Percentage of participants with disabling stroke (VARC-II definitions) at 30 days	30 Days
Device Success Rate	Device Success defined as: Absence of procedural mortality, AND; Correct positioning of a single prosthetic heart valve into the proper anatomical location, AND; Intended performance of the prosthetic heart valve, defined as the absence of patient prosthesis-mismatch and mean gradient < 20 mmHg (or peak velocity < 3 m/sec), AND; Absence of moderate or severe prosthetic valve regurgitation	24 hours to 7 days post implantation
The Percentage of Subjects With no More Than Mild Prosthetic Regurgitation at Early Post Procedure Echocardiogram	The percentage of subjects with no more than mild prosthetic regurgitation at early post procedure echocardiogram as assessed by echo core laboratory	24 hours to 7 days post implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With VARC II Combined Safety Endpoint Event at 30 Days	VARC II composite safety endpoint includes the following components: All-cause mortality; All stroke (disabling and non-disabling); Life-threatening bleeding; Acute kidney injury: stage 2 or 3 (including renal replacement therapy).; Coronary artery obstruction requiring intervention.; Major vascular complication.; Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR)	30 days post-implantation
Percentage of Participants With Life Threatening or Disabling Bleeding	Percentage of participants with life threatening or disabling bleeding - see VARC-2 definitions for classification details	30 days post-implantation
Percentage of Participants With Major Vascular Complication	Percentage of participants with Major vascular complication - see VARC-2 definitions for additional details	30 days
Percentage of Participants With Acute Kidney Injury: Stage 2 or 3	Percentage of participants with Acute Kidney Injury: Stage 2 or 3 - see VARC-2 definitions for additional details	30 days
Percentage of Participants With Coronary Artery Obstruction	Percentage of participants with coronary artery obstruction - see VARC-2 definitions for additional details	30 days
Percentage of Subjects With Valve-related Dysfunction Requiring Repeat Procedure	Percentage of subjects with valve-related dysfunction requiring repeat procedure - see VARC-2 definitions for additional details	30 days
Percentage of Subjects With Permanent Pacemaker Implant at 30 Days	Percentage of subjects with new permanent pacemaker implant at 30 days.	30 days
Percentage of Resheath and Recapture Success	Successful resheathing is defined as Evolut R TAV (including frame) was resheathed into the capsule of the delivery cathether to the desired amount intended, as verified by fluoroscopy. Successful recapture is defined as the entire Evolut R TAV (including frame) is resheathed into the capsule of the delivery catheter until there is no gap between the capsule and the tip, as verified by fluoroscopy.	Implant procedure
Hemodynamic Performance Metrics - Mean Gradient	Mean gradient (mmHg) as measured by transthoracic echocardiogram and assessed by echo core laboratory	30 days
Hemodynamic Performance Metrics- Aortic Valve Area	Aortic valve area as measured by transthoracic echocardiogram and assessed by echo core laboratory	30 Days
Hemodynamic Performance Metrics - Total Prosthetic Regurgitation Graded as None/Trace	Total prosthetic regurgitation (none/trace) as measured by transthoracic echocardiogram and assessed by echo core laboratory	30 days

Collaborators and Investigators

• Sponsor: Medtronic Cardiovascular
• Investigators: Principal Investigator: Mathew R Williams, MD, NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: April 18, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 21, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: 10211838DOC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED