Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial

The PORTICO pivotal IDE trial will include a randomized cohort of 750 subjects enrolled at up to 70 investigational sites in the United States and Australia. Patients will be randomized (1:1) to receive the SJM Portico Transcatheter Heart Valve and Delivery Systems (Portico) or any FDA-approved, commercially-available Transcatheter Aortic Valve Replacement (TAVR) System. The randomized cohort will be tested for two co-primary endpoints at 30 days (primary safety endpoint) and 1 year (primary effectiveness endpoint). At the time of the primary randomized cohort analysis, the risk cohorts will be combined and analysis will be conducted on the intention-to-treat (n=750) population.

The FlexNav Delivery System study will be conducted as a separate arm of the PORTICO IDE trial and will include up to 200 high or extreme risk subjects; including a minimum of 100 analysis subjects. The study will characterize the safety of the next-generation Portico Delivery System ("FlexNav™ Delivery System"). The primary analysis cohort will include FlexNav analysis subjects.

The IDE Valve-in-Valve registry will enroll up to 100 high or extreme risk subjects with a failed surgical bioprosthesis who are eligible to receive a Portico Transcatheter Heart Valve.

All subjects enrolled in the PORTICO pivotal IDE trial will undergo follow-up at baseline, peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, 12-months and then annually through 5-years.

Inclusion criteria

• Subjects must have co-morbidities such that the surgeon and cardiologist Co-Investigators concur that the predicted risk of operative mortality is ≥15% or a minimum Society of Thoracic Surgeons (STS) score of 8%. A candidate who does not meet the STS score criteria of ≥ 8% can be included in the study if a peer review by at least two surgeons concludes and documents that the patient's predicted risk of operative mortality is ≥15%. The surgeon's assessment of operative comorbidities not captured by the STS score must be documented in the study case report form as well as in the patient medical record.
• Subject is 21 years of age or older at the time of consent.
• Subject has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient >40 mmHg or jet velocity greater than 4.0 m/s or Doppler Velocity Index <0.25 and an initial aortic valve area (AVA) of ≤ 1.0 cm2 (indexed effective orifice area (EOA) ≤ 0.6 cm2/m2). (Qualifying AVA baseline measurement must be within 60 days prior to informed consent).
• Subject has symptomatic aortic stenosis as demonstrated by New York Heart Association (NYHA) Functional Classification of II, III, or IV.
• The subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
• The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
• Subject's aortic annulus is 19-27mm diameter as measured by computerized tomography (CT) conducted within 12 months prior to informed consent. Note: if CT is contraindicated and/or not possible to be obtained for certain subjects, a 3D echo and non-contrast CT of chest and abdomen/pelvis may be accepted if approved by the subject selection committee.

For a subject to be considered an Extreme Risk candidate they must meet # 2, 3, 4, 5, 6, 7 of the above criteria, and

• The subject, after formal consults by a cardiologist and two cardiovascular surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the probability of death or serious, irreversible morbidity should exceed 50%. The surgeons' consult notes shall specify the medical or anatomic factors leading to that conclusion and include a printout of the calculation of the STS score to additionally identify the risks in these patients.

Exclusion criteria

• Evidence of an acute myocardial infarction (defined as: ST Segment Elevation as evidenced on 12 Lead ECG) within 30 days prior to index procedure.
• Aortic valve is a congenital unicuspid or congenital bicuspid valve or is non-calcified as verified by echocardiography.
• Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation 3-4+).
• Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to index procedure.
• Pre-existing prosthetic heart valve or other implant in any valve position, prosthetic ring, severe circumferential mitral annular calcification (MAC) which is continuous with calcium in the left ventricular outflow tract (LVOT), severe (greater than 3+) mitral insufficiency, or severe mitral stenosis with pulmonary compromise. Subjects with pre-existing surgical bioprosthetic aortic heart valve should be considered for the Valve-in-Valve registry.
• Blood dyscrasias as defined: leukopenia (WBC<3000 mm3), acute anemia (Hb < 9 g/dL), thrombocytopenia (platelet count <50,000 cells/mm³).
• History of bleeding diathesis or coagulopathy.
• Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
• Untreated clinically significant coronary artery disease requiring revascularization.
• Hemodynamic instability requiring inotropic support or mechanical heart assistance.
• Need for emergency surgery for any reason.
• Hypertrophic cardiomyopathy with or without obstruction (HOCM).
• Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram.
• Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
• Active peptic ulcer or upper gastrointestinal (GI) bleeding within 3 months prior to index procedure.
• A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine (Ticlid), or clopidogrel (Plavix), or sensitivity to contrast media which cannot be adequately premedicated.
• Recent (within 6 months prior to index procedure date) cerebrovascular accident (CVA) or a transient ischemic attack (TIA).
• Renal insufficiency (creatinine > 3.0 mg/dL) and/or end stage renal disease requiring chronic dialysis.
• Life expectancy < 12 months from the time of informed consent due to non-cardiac co-morbid conditions.
• Significant aortic disease, including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5cm or greater; marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick [> 5 mm], protruding or ulcerated) or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe "unfolding" and tortuosity of the thoracic aorta (applicable for transfemoral patients only).
• Native aortic annulus size < 19 mm or > 27 mm per the baseline diagnostic imaging.
• Aortic root angulation > 70° (applicable for transfemoral patients only).
• Currently participating in an investigational drug or device study.
• Active bacterial endocarditis within 6 months prior to the index procedure.
• Bulky calcified aortic valve leaflets in close proximity to coronary ostia.
• Non-calcified aortic annulus
• Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath such as severe obstructive calcification, or severe tortuosity (applicable for transfemoral patients only).

Additional Exclusion Criteria (Transcatheter Access Related)

For selection of an appropriate alternative access delivery method, subjects were screened using the following access specific exclusion criteria:

Transaortic (TAo) Subject Cohort Specific Exclusion Criteria

• Subject has pre-existing patent RIMA graft that would preclude access.
• Subject has a hostile chest or other condition that complicates transaortic access.
• Subject has a porcelain aorta, defined as an extensive circumferential calcification of the ascending aorta that would complicate TAo access.

Additional exclusion criteria for transaortic access using the FlexNav™ Delivery System:

• Subject has a distance between the annular plane and the aortic access site <7 cm (2.8")
• Subject has a distance between the annular plane and the separate introducer sheath distal tip <6 cm (2.4")

Subclavian/Axillary Subject Cohort Specific Exclusion Criteria

• Subject's access vessel (subclavian/axillary) diameter will not allow for introduction of the applicable 18 Fr or 19 Fr delivery system.
• Subject's subclavian/axillary arteries have severe calcification and/or tortuosity.
• Subject's aortic root angulation is:

• Left Subclavian/Left Axillary: >70◦
• Right Subclavian/Right Axillary: >30◦
• Subject has a history of patent LIMA/RIMA graft that would preclude access

Additional exclusion criteria for subclavian/axillary access using the FlexNav™ Delivery System:

• Subject's access vessel (subclavian/axillary) has a distance between the annular plane and the integrated sheath distal tip <17 cm (6.7")
• Subject's access vessel requires the delivery system to be advanced through a separate introducer sheath