Perceval Sutureless Implant Versus Standard-Aortic Valve Replacement

Study Overview
=================
Brief Summary
-----------------
Prospective, randomized, stratified non blinded multi-center, international, post market trial assessed in a non-inferiority study. The trial has a flexible sample size that will be determined adaptively. The trial will enroll up to 1234 subjects, but accrual may stop earlier at approximately 900 or 1050 subjects These subjects will be enrolled at approximately 60 worldwide investigational sites where the device is commercially available The primary objective of this trial is to test the safety and efficacy of Perceval versus standard sutured stented bioprosthetic aortic valves among the intended trial population.

Detailed Description
-----------------
PERSIST-AVR is designed to collect data on sutureless valve (Perceval sutureless aortic heart valve), a new type of biological aortic valve, comparing data with standard biological aortic valve, considered the gold standard for aortic valve replacement. This prospective, randomized international multicenter study is planned to demonstrate, as primary endpoint, the non inferiority of Major Adverse Cardiac and Cerebrovascular (MACCE) events at one year while showing superiority in resource consumptions at hospital discharge in patients treated with Perceval valve when compared to standard aortic valve replacement. The study is planned to cover the lack of prospective, randomized comparison data between sutureless valve and standard aortic biological sutured valve. The trial has a flexible sample size that will be determined adaptively. The trial will enroll up to 1234 subjects, but accrual may stop earlier at approximately 900 or 1050 subjects. These subjects will be enrolled at approximately 60 worldwide investigational sites where the device is commercially available. The primary endpoint will be reached at 1 year FU and, consequently, the planned primary analysis will be performed 12 months following the end of accrual. The be part of the trial, investigational sites should have demonstrated experience with the implantation of the Perceval and able to implement the requirements of the study protocol.. All subjects with severe symptomatic aortic stenosis or steno-insufficiency who are candidates for surgical replacement of their native aortic valve according to established guidelines in current medical practice and as specified in the Perceval valve Instruction for Use (IFU) are the intended population for inclusion in this randomized trial.

Official Title
-----------------
Perceval Sutureless Implant Versus Standard-Aortic Valve Replacement A Controlled Randomized Trial in the Surgical Treatment of Aortic Valve Disease

Conditions
-----------------
Aortic Valve Disease, Aortic Stenosis

Intervention / Treatment
-----------------
* Device: Perceval valve
* Device: other stented biological valve


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject has an indication for treatment by valve replacement with a bioprosthesis according to the IFU, through either full sternotomy or mini-sternotomy. The subject has aortic valve disease that can be treated with a commercially available Perceval valve size, based on preoperative CT-scan. The subject has: critical aortic valve area defined as an initial aortic valve area of ≤1.0 cm2 or aortic valve area index < 0.6 cm2/m2 AND Mean gradient > 40 mmHg or Vmax > 4 m/sec by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization [or with dobutamine stress, if subject has a left ventricular ejection fraction (LVEF) <55%] or velocity ratio < 0.25; The subject is symptomatic due to aortic stenosis with functional class of New York Heart Association (NYHA) II or higher. The subject has signed the informed consent. The subject is of legal minimum age. The subject will be available for postoperative follow-up beyond one year. Exclusion Criteria: The subject has a contraindication for treatment by the Perceval valve or by a bioprosthetic aortic valve as stated in the IFU. The subject has aneurismal dilation or dissection of the ascending aortic wall. The subject is scheduled for concomitant procedures other than Coronary Aortic Bypass Graft (CABG), myectomy with or without aortic annulus enlargement The subject has congenital bicuspid (i.e. Sievers type 0) or unicuspid aortic valve. Anatomical structures not suitable for Perceval valve such as: aortic root enlargement, where the ratio between the diameter of the sino-tubular junction and the annulus diameter is > 1.3. The subject has a prosthetic heart valve in any position, including mitral valve repair. The subject has a stroke or myocardial infarction (STEMI and NSTEMI) within 30 days prior to the planned valve implant surgery. The subject has active endocarditis, myocarditis, or sepsis. The subject is in cardiogenic shock manifested by low cardiac output and needing hemodynamic support. The subject is allergic to nickel alloys. The subject is already included in another clinical trial that could confound the results of this clinical investigation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perceval<br>The Perceval sutureless aortic heart valve (Perceval valve) is a bioprosthesis manufactured with bovine pericardium and assembled on a Nitinol stent. The Perceval valve is designed to offer an alternative to surgically implanted flexible prostheses (stented and stentless biological valves). A special feature of the device is that it is self-anchoring and does not require sutures to be fixed to the implant site. | Device: Perceval valve<br>* Sutureless Aortic Biological Valve<br>|
| Active Comparator: other Stented biological valves<br>The comparator will be other commercially approved standard biological sutured stented valves, both bovine and porcine. The choice of the comparator tissue valve will be at the discretion of the participating investigators. | Device: other stented biological valve<br>* Any biological stented valves available on the market (Edwards, Medtronic, St.Jude, LivaNova, Labcor)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Freedom From Major Adverse Cardiac and Cerebrovascular Events (MACCE) | The primary endpoint is freedom from MACCE (composite endpoint of all cause death, myocardial infarction, stroke, and valve re-intervention) at one year based on Clinical Event Committee (CEC) adjudication. | 1 year post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical Times | Cross clamp time during index procedure Cardiopulmonary bypass time during index procedure Start time and finish time were collected for operative room time procedure and calculated for each subject. Mean was calculated and reported in the results sections | Intra-operative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sutureless valve