Assessment of the St Jude Medical Portico Resheathable Aortic Valve System-Alternative Access

Study Overview
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Brief Summary
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Expand the indication of the Portico TF Delivery System and obtain approval of the Alternative Access Delivery System

Detailed Description
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Expand the indication of the Portico TF Delivery System and obtain approval of the Alternative Access Delivery System to place a Portico transcatheter aortic valve through an alternative access site, specifically subclavian/axillary or transaortic (TAo) in subjects with symptomatic severe native aortic stenosis who are considered high surgical risk

Official Title
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Assessment of the St Jude Medical Portico Resheathable Aortic Valve System-Alternative Access

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Transaortic TAVR Implant
* Device: Subclavian /Axillary TAVR implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided written informed consent prior to uploading CT scan to core lab. Subject is ≥ 18 years of age or legal age in host country. Subject's aortic annulus diameter meets the range indicated in the Instructions for Use as measured by multislice CT conducted within 180 days prior to the index procedure. Subject has senile degenerative aortic stenosis seen by echocardiography within 90 days of index procedure as measured by: mean gradient >40 mmHg Peak velocity ≥ 4.0 m/s Doppler Velocity Index <0.25 Aortic valve area (AVA) of ≤ 1.0 cm2 or indexed EOA ≤ 0.6 cm2/m2). Subject has symptomatic aortic stenosis as demonstrated by NYHA Functional Classification of Class II, or greater or other symptoms of aortic stenosis (e.g. syncope). Subject is deemed high operable risk and preferred TAVI delivery route is alternate access (subclavian/axillary or direct aortic) per the medical opinion of the center's heart team and confirmed by SSC. High risk is defined as an STS mortality > 8% or documented heart team agreement ≥ high risk for SAVR due to frailty or co-morbidities Exclusion Criteria: Subject is unwilling or unable to comply with all study-required follow-up evaluations. Subject has a documented history of a cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6 months (less than or equal to 180 days) prior to the index procedure. Subject has carotid artery disease requiring intervention. Subject has evidence of a myocardial infarction (MI) within 30 days prior to patient index procedure. Subject has a native aortic valve that is congenitally unicuspid, bicuspid, quadricuspid or non-calcified as seen by echocardiography. Subject has severe mitral valvular regurgitation. Subject has severe mitral stenosis. Subject has a pre-existing prosthetic cardiac device, valve, or prosthetic ring in any position. Subject refuses any blood product transfusion. Subject has resting left ventricular ejection fraction (LVEF) less than 20%. Subject has documented, untreated symptomatic coronary artery disease (CAD) requiring revascularization. Subject has had a percutaneous interventional or other invasive cardiovascular or peripheral vascular procedure less than or equal to 14 days prior to index procedure. Subject has severe basal septal hypertrophy that would interfere with transcatheter aortic valve placement. Subject has a history of, or is currently diagnosed with, endocarditis. There is imaging evidence of intracardiac mass, thrombus, or vegetation. Subject is considered hemodynamically unstable (requiring inotropic support or mechanical heart assistance). Subject is in acute pulmonary edema or requiring intravenous diuretic therapy to stabilize heart failure. Subject with severe pulmonary disease as determined by STS score. Subject is on chronic oral steroid therapy. Subject has a documented hypersensitivity or contraindication to anticoagulant or antiplatelet medication. Subject has renal insufficiency as evidenced by a serum creatinine greater than 3.0 mg/dL (265.5 µmol/L) or end-stage renal disease requiring chronic dialysis. Subject has morbid obesity defined as a BMI greater than or equal to 40. Subject has ongoing infection or sepsis. Subject has uncontrolled blood dyscrasias as defined: leukopenia (WBC<3000 mm3), acute anemia (Hb<9 mg/dL), thrombocytopenia (platelet count <50,000 cells/mm3,). Anatomy falling outside the recommended values in the IFU, unless specifically approved by the Subject Selection Committee. Subject has an active peptic ulcer or has had gastrointestinal (GI) bleeding within 90 days prior to the index procedure. Subject is currently participating in another investigational drug or device study, unless approved by the Sponsor. Subject has/had emergency surgery for any reason within 30 days of the index procedure. Subject has a life expectancy less than 1 year. Subject has other medical, social or psychological conditions that, in the opinion of the Principal Investigator or the Subject Selection Committee, preclude the subject from study participation. Subject is diagnosed with a state of dementia which would fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits. Subject has a documented allergy to contrast media that cannot adequately be treated, nitinol alloys, porcine tissue, or bovine tissue. Significant aortic disease including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5cm or greater Subjects with severe pulmonary hypertension and severe RV dysfunction Subjects with hypertrophic cardiomyopathy Transaortic Subject Cohort Specific Exclusion Criteria Subjects are not eligible for participation in the TAo access arm if they meet any of the following exclusion criteria: Subject has a chest condition (anatomical or otherwise) that prevents TAo access. Subject has pre-existing patent RIMA graft that would preclude access. Subject has a porcelain aorta, defined as an extensive circumferential calcification of the ascending aorta that would complicate TAo access. Subclavian/Axillary Subject Cohort Specific Exclusion Criteria Subjects are not eligible for participation in the subclavian/axillary access arm if they meet any of the following exclusion criteria: Subject's access vessel (subclavian/axillary) diameter will not allow for introduction of the 18/19 Fr delivery system. Subject's subclavian/axillary arteries have severe calcification and/or tortuosity. Subject has a history of LIMA/RIMA graft that would preclude access

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Portico TF and ALT Delivery System
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subclavian/axillary<br>Subclavian/axillary access route | Device: Subclavian /Axillary TAVR implant<br>* Subclavian /Axillary TAVR implant<br>|
| Experimental: Transaortic<br>Transaortic access route | Device: Transaortic TAVR Implant<br>* Transaortic TAVR implant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major Vascular Complications | Major Vascular complication is defined as Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, or new apical aneurysm/pseudo-aneurysm or Access site or access-related vascular injury leading to death, life-threatening or major bleeding, visceral ischaemia or neurological impairment or Distal embolization from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage or The use of unplanned endovascular or surgical intervention associated with death, major bleeding, visceral ischaemia or neurological impairment or Any new ipsilateral lower extremity ischemia documented by patient symptoms, physical exam, and/or decreased or absent blood flow on lower extremity angiogram or Surgery for access site-related nerve injury or Permanent access site-related nerve injury | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of All- Cause Mortality |  | 30 Days | 
| Number of All- Cause Mortality |  | 1 Year | 
| Cardiovascular Mortality | Any 1 of the following criteria: Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac tamponade, worsening heart failure) Death caused by non-coronary vascular conditions such as neurological events, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular disease. All procedure-related deaths, including those related to a complication of the procedure or treatment for a complication of the procedure All valve-related deaths including structural or nonstructural valve dysfunction or other valve-related adverse events Sudden or unwitnessed death Death of unknown cause | 30 Days | 
| Cardiovascular Mortality | Any 1 of the following criteria: Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac tamponade, worsening heart failure) Death caused by non-coronary vascular conditions such as neurological events, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular disease. All procedure-related deaths, including those related to a complication of the procedure or treatment for a complication of the procedure All valve-related deaths including structural or nonstructural valve dysfunction or other valve-related adverse events Sudden or unwitnessed death Death of unknown cause | 1 year | 
| Number of Participants With Disabling Stroke | Disabling stroke is an mRS score of 2 or more at 90 days and an increase of at least 1 mRS category from an individual's prestroke baseline | 30 Days | 
| Number of Participants With Disabling Stroke | Disabling stroke is an mRS score of 2 or more at 90 days and an increase of at least 1 mRS category from an individual's prestroke baseline | 1 Year | 
| Number of Participants With Non-disabling Strokes | Non-disabling is an mRS score of <2 at 90 days or 1 that does not result in an increase of at least 1 mRS category from an individual's prestroke baseline | 30 Days | 
| Number of Participants With Non-disabling Strokes | Non-disabling is an mRS score of <2 at 90 days or 1 that does not result in an increase of at least 1 mRS category from an individual's prestroke baseline | 1 Year | 
| Number of Participants With Life Threatening Bleeding Requiring Transfusion | Life threatening bleeding requiring transfusion Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0 g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing hospitalization or permanent injury, or requiring surgery AND Does not meet criteria of life-threatening or disabling bleeding | 30 Days | 
| Number of Participants With Life Threatening Bleeding Requiring Transfusion | Life threatening bleeding requiring transfusion Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0 g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing hospitalization or permanent injury, or requiring surgery AND Does not meet criteria of life-threatening or disabling bleeding | 1 Year | 
| Number of Participants With Acute Kidney Injury Requiring Dialysis | Increase in serum creatinine to greater than or equal to 300% (3 X increase compared with baseline) or serum creatinine of ≥ 4.0 mg/dL (354 mmol/L) with an acute increase of at least 0.5 mg/dL (44 mmol/L)or Urine output <0.3 mL/kg per hour for ≥24 hours or anuria for ≥12 hours. Patients receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria | 30 Days | 
| Number of Participants With Acute Kidney Injury Requiring Dialysis | Increase in serum creatinine to greater than or equal to 300% (3 X increase compared with baseline) or serum creatinine of ≥ 4.0 mg/dL (354 mmol/L) with an acute increase of at least 0.5 mg/dL (44 mmol/L)or Urine output <0.3 mL/kg per hour for ≥24 hours or anuria for ≥12 hours. Patients receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria | 1 Year | 
| Number of Participants With Composite of Periprocedural Encephalopathy, All Stroke and All TIA | Stroke is an acute symptomatic episode of neurological dysfunction attributed to a vascular cause. Transient Ischemic Attack (TIA) is a transient (less than 24 hrs) episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. No evidence of infarction if imaging performed. Encephalopathy is defined as altered mental state (e.g., seizures, delirium, confusion, hallucinations, dementia, coma, psychiatric episode). | 30 Days | 
| Number of Participants With Composite of Periprocedural Encephalopathy, All Stroke and All TIA | Stroke is an acute symptomatic episode of neurological dysfunction attributed to a vascular cause. Transient Ischemic Attack (TIA) is a transient (less than 24 hrs) episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. No evidence of infarction if imaging performed. Encephalopathy is defined as altered mental state (e.g., seizures, delirium, confusion, hallucinations, dementia, coma, psychiatric episode). | 1 Year | 
| Number of Participants With Moderate and Severe Aortic Regurgitation |  | 1 year | 
| Change in NYHA Class From Baseline to 30 Days | New York Heart Association (NYHA) functional classification provides a way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina pain. Class I. Patients with cardiac disease but without resulting limitation of physical activity. Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. | Baseline to 30 days | 
| Change in Six Minute Walk Test From Baseline as Compared to 30 Days | The Six Minute Walk Test (6MWT)measures the distance that a patient can walk in a period of 6 minutes. The distance walked is measured in meters. This test measures the patients' functional status. The more meters a patient can walk over baseline indicates improvement in functional status. | Baseline to 30 days | 
| Change in Effective Orifice Area From Baseline as Compared to 30 Days | Effective Orifice Area of the prosthetic valve measured via echocardiography to determine physiological area of blood flow through the valve. | Baseline to 30 days. | 
| Number of Participants With Overall Acute Device Success | Acute device success is defined as a subject who achieves a) successful vascular access, delivery and deployment of the device and successful retrieval of the delivery system, b) correct position of the device in the proper anatomical location, c) intended performance of the prosthetic heart valve, and d) only 1 valve implanted in the proper anatomical location. Device success is a 'technical' composite endpoint meant to characterize the acute device and procedural factors which underlie vascular access, delivery, and performance of the TAVI system. Echocardiography should be routinely utilized as the standard for measuring prosthetic valve stenosis and regurgitation immediately after TAVI, and should always be performed in a resting state, either within 24-48 h after the index procedure or before hospital discharge. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAVI, Valvular heart disease, Transcatheter aortic valve implantation