CoreValve® System Australia/New Zealand Clinical Study

Study Overview
=================
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.

Official Title
-----------------
CoreValve® System Australia/New Zealand Clinical Study

Conditions
-----------------
Aortic Valve Stenosis

Intervention / Treatment
-----------------
* Device: Medtronic CoreValve® System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Documented severe aortic valve stenosis Access vessel diameter >6 mm as defined pre procedure via angiographic measure Aortic valve annulus diameter ≥ 20 mm and < 29 mm as defined pre procedure by echocardiographic measure Ascending aorta diameter ≤ 43 mm at the sino-tubular junction 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) 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: Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, clopidogrel, nitinol, porcine products, or contrast media which cannot be adequately pre-medicated Any sepsis, including active endocarditis. Recent myocardial infarction (<30 days) Any left ventricular or atrial thrombus as determined pre procedure by echocardiography Uncontrolled atrial fibrillation Mitral or tricuspid valvular insufficiency (> grade II) Previous aortic valve replacement (mechanical valve or stented bioprosthetic valve) Evolutive or recent CVA (cerebrovascular accident), (<3 months) Femoral, iliac or aortic vascular condition (e.g. stenosis, tortuosity), that make impossible insertion and endovascular access to the aortic valve Symptomatic carotid or vertebral arteries narrowing (> 70%) disease Abdominal or thoracic aortic aneurysm Bleeding diathesis or coagulopathy, or patient will refuse blood transfusion Evolutive disease with life expectancy less than one year Creatinine clearance < 20 ml/min Active gastritis or known peptic ulcer disease Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medtronic CoreValve® System Implantation<br>Patients with symptomatic severe aortic stenosis who have an elevated surgical risk | Device: Medtronic CoreValve® System<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 30 days | 
| 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 | 24-48 hours after the procedure or before the discharge | 
| 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). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality | is defined per Valve Academic Research Consortium-1 consensus document (VARC-1), including Cardiovascular and non-cardiovascular mortality. | 30 days | 
| Myocardial Infarction | Included Q-wave and non-Q-wave. | 30 days | 
| Stroke | Is a neurological deficit lasting more than 24 hours, or lasting 24 hours or less with a brain imaging study showing infarction. | 30 days | 
| Re-intervention | Any emergent surgical or percutaneous interventional catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve. | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aortic Valve Stenosis, Aortic Valve Insufficiency