Aortic Valve Stenosis
Conditions
Keywords
Aortic Valve Stenosis, Aortic Valve Insufficiency
Brief summary
To evaluate the performance, efficacy and safety of the percutaneous implantation of the CoreValve® prosthetic aortic valve in patients with severe symptomatic native aortic valve stenosis that have an elevated surgical risk
Detailed description
Prospective, non-randomized, single-arm multi-center trial conducted under a common protocol at 10 centers in Australia and New Zealand.
Interventions
DEVICEMedtronic CoreValve® System
The Medtronic CoreValve® System device is designed to replace the native aortic valve without the requirement for open heart surgery and without concomitant surgical removal of the failed native valve in patients with symptomatic severe aortic stenosis who have an elevated surgical risk
Sponsors
Medtronic Australasia
Medtronic Cardiovascular
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented severe aortic valve stenosis 2. Access vessel diameter \>6 mm as defined pre procedure via angiographic measure 3. Aortic valve annulus diameter ≥ 20 mm and \< 29 mm as defined pre procedure by echocardiographic measure 4. Ascending aorta diameter ≤ 43 mm at the sino-tubular junction 5. Native aortic valve disease, defined as valve stenosis with an aortic valve area\<1cm2 (\<0.6cm2 /m2) as defined pre procedure by echocardiographic measure AND (Assessment of Surgical Risk) Age ≥ 80 years AND/OR Surgical risk calculated with logistic EuroSCORE ≥ 20%, AND/OR Age ≥ 65 years with one or two (but not more than 2) of the following criteria: * Cirrhosis of the liver (Child class A or B) * Pulmonary insufficiency : VMS \< 1 liter * Previous cardiac surgery (CABG, valvular surgery) * Porcelain aorta * Pulmonary hypertension \> 60 mmHg and high probability of cardiac surgery for other than valve replacement * Recurrent pulmonary embolus * Right ventricular insufficiency * Thoracic burning sequelae contraindicating open chest surgery * History of mediastinum radiotherapy * Severe connective tissue disease resulting in a contraindication to surgery * Cachexia (clinical impression) 6. Study subjects must be willing and able to attend all follow-up visits within specified visit windows, and agree to undergo all protocol evaluations at each visit
Exclusion criteria
1. Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, clopidogrel, nitinol, porcine products, or contrast media which cannot be adequately pre-medicated 2. Any sepsis, including active endocarditis. 3. Recent myocardial infarction (\<30 days) 4. Any left ventricular or atrial thrombus as determined pre procedure by echocardiography 5. Uncontrolled atrial fibrillation 6. Mitral or tricuspid valvular insufficiency (\> grade II) 7. Previous aortic valve replacement (mechanical valve or stented bioprosthetic valve) 8. Evolutive or recent CVA (cerebrovascular accident), (\<3 months) 9. Femoral, iliac or aortic vascular condition (e.g. stenosis, tortuosity), that make impossible insertion and endovascular access to the aortic valve 10. Symptomatic carotid or vertebral arteries narrowing (\> 70%) disease 11. Abdominal or thoracic aortic aneurysm 12. Bleeding diathesis or coagulopathy, or patient will refuse blood transfusion 13. Evolutive disease with life expectancy less than one year 14. Creatinine clearance \< 20 ml/min 15. Active gastritis or known peptic ulcer disease 16. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) Rate | 30 days | Defined as a composite of all cause death, myocardial infarction(MI) (Q-wave & non-Q-wave), stroke, and re-intervention (defined as any emergent cardiac surgery or percutaneous re-intervention catheter procedure that repairs, otherwise alters or adjusts or replaces a previously implanted valve) |
| Percentage of Participants With Overall Device Success | 24-48 hours after the procedure or before the discharge | * Vascular access, delivery and deployment of the device, and retrieval of the delivery system * Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function) * Intended performance of the prosthetic valve (aortic valve area \> 1.2 cm2 (by echocardiography using the continuity equation) and mean aortic valve gradient \< 20 mmHg, without moderate or severe prosthetic valve aortic regurgitation) * Only one valve implanted * No occurrence of in-hospital MACCE |
| Cardiac-related Death | 30 days | Defined as all death resulting from a cardiac cause or complications of a cardiac procedure and / or death of an unknown cause; this category includes valve-related deaths and non-valve-related cardiac deaths (e.g. congestive heart failure, acute myocardial infarction, documented fatal arrhythmias). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality | 30 days | is defined per Valve Academic Research Consortium-1 consensus document (VARC-1), including Cardiovascular and non-cardiovascular mortality. |
| Re-intervention | 30 days | Any emergent surgical or percutaneous interventional catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve. |
| Myocardial Infarction | 30 days | Included Q-wave and non-Q-wave. |
| Stroke | 30 days | Is a neurological deficit lasting more than 24 hours, or lasting 24 hours or less with a brain imaging study showing infarction. |
Countries
Australia, New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Medtronic CoreValve® System Implantation Patients with symptomatic severe aortic stenosis who have an elevated surgical risk
Medtronic CoreValve® System: The Medtronic CoreValve® System device is designed to replace the native aortic valve without the requirement for open heart surgery and without concomitant surgical removal of the failed native valve in patients with symptomatic severe aortic stenosis who have an elevated surgical risk | 634 |
| Total | 634 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 113 |
| Overall Study | Withdrawal by Subject | 40 |
Baseline characteristics
| Characteristic | Medtronic CoreValve® System Implantation |
|---|---|
| Age, Continuous | 84.1 years STANDARD_DEVIATION 5.6 |
| Region of Enrollment Australia | 523 participants |
| Region of Enrollment New Zealand | 111 participants |
| Sex: Female, Male Female | 281 Participants |
| Sex: Female, Male Male | 353 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 583 / 634 |
| serious Total, serious adverse events | 534 / 634 |
Outcome results
Primary
Cardiac-related Death
Defined as all death resulting from a cardiac cause or complications of a cardiac procedure and / or death of an unknown cause; this category includes valve-related deaths and non-valve-related cardiac deaths (e.g. congestive heart failure, acute myocardial infarction, documented fatal arrhythmias).
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | Cardiac-related Death | 0.035 probability of events at 30 days |
Primary
Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) Rate
Defined as a composite of all cause death, myocardial infarction(MI) (Q-wave & non-Q-wave), stroke, and re-intervention (defined as any emergent cardiac surgery or percutaneous re-intervention catheter procedure that repairs, otherwise alters or adjusts or replaces a previously implanted valve)
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) Rate | 0.099 probability of events at 30 days |
Primary
Percentage of Participants With Overall Device Success
* Vascular access, delivery and deployment of the device, and retrieval of the delivery system * Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function) * Intended performance of the prosthetic valve (aortic valve area \> 1.2 cm2 (by echocardiography using the continuity equation) and mean aortic valve gradient \< 20 mmHg, without moderate or severe prosthetic valve aortic regurgitation) * Only one valve implanted * No occurrence of in-hospital MACCE
Time frame: 24-48 hours after the procedure or before the discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | Percentage of Participants With Overall Device Success | 52.6 % of participants with device success |
Secondary
All-Cause Mortality
is defined per Valve Academic Research Consortium-1 consensus document (VARC-1), including Cardiovascular and non-cardiovascular mortality.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | All-Cause Mortality | 0.038 probability of events at 30 days |
Secondary
Myocardial Infarction
Included Q-wave and non-Q-wave.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | Myocardial Infarction | 0.021 probability of events at 30 days |
Secondary
Re-intervention
Any emergent surgical or percutaneous interventional catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | Re-intervention | 0.019 probability of events at 30 days |
Secondary
Stroke
Is a neurological deficit lasting more than 24 hours, or lasting 24 hours or less with a brain imaging study showing infarction.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtronic CoreValve® System Implantation | Stroke | 0.043 probability of events at 30 days |