Aortic Valve Stenosis
Conditions
Brief summary
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.
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.
Interventions
DEVICECoreValve Evolut 34R TAVR system
The CoreValve Evolut 34R System is a transcatheter aortic valve implantation system comprised of the following three components: 1. Evolut 34R Transcatheter Aortic Valve (TAV) 2. EnVeo R Delivery Catheter System (DCS) with EnVeo R InLine Sheath 3. EnVeo R Loading System (LS)
Sponsors
Medtronic Cardiovascular
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With All-cause Mortality | 30 Days | Percentage of participants with all-cause mortality at 30 days |
| Percentage of Participants With Stroke (Disabling) | 30 Days | Percentage of participants with disabling stroke (VARC-II definitions) at 30 days |
| Device Success Rate | 24 hours to 7 days post implantation | 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 |
| The Percentage of Subjects With no More Than Mild Prosthetic Regurgitation at Early Post Procedure Echocardiogram | 24 hours to 7 days post implantation | The percentage of subjects with no more than mild prosthetic regurgitation at early post procedure echocardiogram as assessed by echo core laboratory |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Coronary Artery Obstruction | 30 days | Percentage of participants with coronary artery obstruction - see VARC-2 definitions for additional details |
| Percentage of Subjects With Valve-related Dysfunction Requiring Repeat Procedure | 30 days | Percentage of subjects with valve-related dysfunction requiring repeat procedure - see VARC-2 definitions for additional details |
| Percentage of Subjects With Permanent Pacemaker Implant at 30 Days | 30 days | Percentage of subjects with new permanent pacemaker implant at 30 days. |
| Percentage of Participants With VARC II Combined Safety Endpoint Event at 30 Days | 30 days post-implantation | 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) |
| Hemodynamic Performance Metrics - Mean Gradient | 30 days | Mean gradient (mmHg) as measured by transthoracic echocardiogram and assessed by echo core laboratory |
| Hemodynamic Performance Metrics- Aortic Valve Area | 30 Days | Aortic valve area as measured by transthoracic echocardiogram and assessed by echo core laboratory |
| Hemodynamic Performance Metrics - Total Prosthetic Regurgitation Graded as None/Trace | 30 days | Total prosthetic regurgitation (none/trace) as measured by transthoracic echocardiogram and assessed by echo core laboratory |
| Percentage of Resheath and Recapture Success | Implant procedure | 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. |
| Percentage of Participants With Life Threatening or Disabling Bleeding | 30 days post-implantation | Percentage of participants with life threatening or disabling bleeding - see VARC-2 definitions for classification details |
| Percentage of Participants With Major Vascular Complication | 30 days | Percentage of participants with Major vascular complication - see VARC-2 definitions for additional details |
| Percentage of Participants With Acute Kidney Injury: Stage 2 or 3 | 30 days | Percentage of participants with Acute Kidney Injury: Stage 2 or 3 - see VARC-2 definitions for additional details |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CoreValve Evolut 34R TAVR System Treatment of Aortic Stenosis with Medtronic CoreValve Evolut R 34R TAVR System.\>
\> CoreValve Evolut 34R TAVR system: The CoreValve Evolut 34R System is a transcatheter aortic valve implantation system comprised of the following three components:\>
1. Evolut 34R Transcatheter Aortic Valve (TAV)\>
2. EnVeo R Delivery Catheter System (DCS) with EnVeo R InLine Sheath\>
3. EnVeo R Loading System (LS) | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 12-Month | Death | 3 |
| 12-Month | Withdrawal by Subject | 2 |
| 1-Month | Death | 5 |
| 24-Month | Death | 1 |
| 24-Month | Withdrawal by Subject | 1 |
| 36-Month | Death | 8 |
| 36-Month | Withdrawal by Subject | 1 |
| 48-Month | Death | 7 |
| 48-Month | Withdrawal by Subject | 1 |
| 60-Month | Death | 1 |
| 60-Month | Lost to Follow-up | 2 |
| 6-Month | Death | 2 |
| 6-Month | Withdrawal by Subject | 1 |
| Enrollment | Expected Enrollment Met | 2 |
| Enrollment | Inclusion Exclusion not met | 9 |
| Enrollment | Withdrawal by Subject | 1 |
| Procedure | Death | 1 |
Baseline characteristics
| Characteristic | CoreValve Evolut 34R TAVR System | — |
|---|---|---|
| Age, Continuous | 81.8 years STANDARD_DEVIATION 8.2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 60 Participants | — |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 58 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 28 / 60 |
| other Total, other adverse events | 48 / 60 |
| serious Total, serious adverse events | 34 / 60 |
Outcome results
Primary
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
Time frame: 24 hours to 7 days post implantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Device Success Rate | 79.2 percentage of participants |
Primary
Percentage of Participants With All-cause Mortality
Percentage of participants with all-cause mortality at 30 days
Time frame: 30 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With All-cause Mortality | 1.7 percentage of participants |
Primary
Percentage of Participants With Stroke (Disabling)
Percentage of participants with disabling stroke (VARC-II definitions) at 30 days
Time frame: 30 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With Stroke (Disabling) | 0.0 percentage of participants |
Primary
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
Time frame: 24 hours to 7 days post implantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | The Percentage of Subjects With no More Than Mild Prosthetic Regurgitation at Early Post Procedure Echocardiogram | 100.0 percentage of participants |
Secondary
Hemodynamic Performance Metrics- Aortic Valve Area
Aortic valve area as measured by transthoracic echocardiogram and assessed by echo core laboratory
Time frame: 30 Days
Population: Only participants with echo could be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CoreValve Evolut 34R TAVR System | Hemodynamic Performance Metrics- Aortic Valve Area | 2.6 cm2 | Standard Deviation 0.7 |
Secondary
Hemodynamic Performance Metrics - Mean Gradient
Mean gradient (mmHg) as measured by transthoracic echocardiogram and assessed by echo core laboratory
Time frame: 30 days
Population: Only participants with echo could be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CoreValve Evolut 34R TAVR System | Hemodynamic Performance Metrics - Mean Gradient | 6.4 mmHg | Standard Deviation 3.2 |
Secondary
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
Time frame: 30 days
Population: Only participants with echo could be analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Hemodynamic Performance Metrics - Total Prosthetic Regurgitation Graded as None/Trace | 60.3 percentage of participants |
Secondary
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
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With Acute Kidney Injury: Stage 2 or 3 | 0.0 percentage of participants |
Secondary
Percentage of Participants With Coronary Artery Obstruction
Percentage of participants with coronary artery obstruction - see VARC-2 definitions for additional details
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With Coronary Artery Obstruction | 0.0 percentage of participants |
Secondary
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
Time frame: 30 days post-implantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With Life Threatening or Disabling Bleeding | 1.7 percentage of participants |
Secondary
Percentage of Participants With Major Vascular Complication
Percentage of participants with Major vascular complication - see VARC-2 definitions for additional details
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With Major Vascular Complication | 1.7 percentage of participants |
Secondary
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)
Time frame: 30 days post-implantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Participants With VARC II Combined Safety Endpoint Event at 30 Days | 5.0 percentage of participants |
Secondary
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.
Time frame: Implant procedure
Population: Success could only be analyzed in subjects where the resheath/recapture feature was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Resheath and Recapture Success | 100.0 percentage of participants |
Secondary
Percentage of Subjects With Permanent Pacemaker Implant at 30 Days
Percentage of subjects with new permanent pacemaker implant at 30 days.
Time frame: 30 days
Population: Subjects with pre-existing pacemaker or internal cardiac defibrillator were excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Subjects With Permanent Pacemaker Implant at 30 Days | 20.8 percentage of participants |
Secondary
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
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CoreValve Evolut 34R TAVR System | Percentage of Subjects With Valve-related Dysfunction Requiring Repeat Procedure | 0.0 percentage of participants |