PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - XT Intermediate and High Risk

Study Overview
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Brief Summary
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The purpose of this trial is to determine the safety and effectiveness of the Edwards SAPIEN XT transcatheter heart valve and delivery systems which are intended for use in patients with symptomatic, calcific, severe aortic stenosis.

Detailed Description
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The PIIA cohort is a prospective multi-center trial undergoing aortic valve replacement for severe aortic stenosis. Patients randomized to the treatment arm will receive an Edwards SAPIEN XT THV with either transfemoral, transapical or transaortic delivery access. Patients in the control arm will receive a surgical bioprosthetic heart valve via aortic valve replacement surgery. To assure that patients with an STS score ≥ 4% have been selected.

Official Title
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Edwards SAPIEN XT Transcatheter Heart Valve Therapy for Intermediate and High Risk Patients

Conditions
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Symptomatic Severe Aortic Stenosis

Intervention / Treatment
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* Device: TAVR Implantation with SAPIEN XT
* Device: SAVR Implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient >40 mmHg or jet velocity greater than 4.0 m/s and an initial aortic valve area (AVA) of ≤0.8 cm2 or indexed EOA < 0.5 cm2/m2 Qualifying echo must be within 60 days of the date of the procedure. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater. The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient. The study patient or the study patient's legal representative 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 study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up. Study patient agrees to undergo surgical aortic valve replacement (SAVR) - if randomized to control treatment. Exclusion Criteria Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)]. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+). Preexisting mechanical or bioprosthetic valve in any position (except NR3). Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease). Implantation of a permanent pacemaker or ICD (S3 Cohort only) is not excluded. Heart team assessment of inoperability (including examining cardiac surgeon).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PIIA - SAPIEN XT<br>PIIA is operable group | Device: TAVR Implantation with SAPIEN XT<br>* Operable Group with SAPIEN XT<br>|
| Active Comparator: Control: SAVR<br>SAVR (surgical aortic valve replacement) is the control arm | Device: SAVR Implantation<br>* Control Group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Death or Disabling Stroke to Two Years | All-cause Death or Disabling Stroke (Edwards SAPIEN XT THV vs SAVR) | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Days Alive and Out of Hospital (DAOH) to Two Years | The number of days the patients are alive and out of the hospital. | 2 years | 
| Total Aortic Regurgitation (AR) at 2 Years | Total aortic regurgitation was assessed by the core lab as Grade 0 = None, Grade 1+ = Trace, Grade 2+ = Mild, Grade 3+ = Moderate and Grade 4+ = Severe. Total regurgitation at two year was analyzed in the valve implant population. | 2 years | 
| 6MWT Change From Baseline | Six Minute Walk Test change from baseline to 2 years | Baseline and 2 years | 
| NYHA Classification at 2 Years | New York Heart Association (NYHA), functional classification of heart failure based on how much a patient is limited during physical activity. The rating ranges from I - IV, with the lowest as no limitations and the highest unable to carry on any physical activity without discomfort. | 2 years | 
| Effective Orifice Area (EOA) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SAPIEN XT, Transfemoral, Transapical, Transaortic, NovaFlex, TAVI, Aortic Stenosis, THV, Aortic Valve, Transcatheter Heart Valve, TAVR