Safety and Effectiveness Study of Perceval S Valve for Extended CE Mark

Perceval S Valve Clinical Trial for Extended CE Mark

The primary objective of this clinical investigation is to assess the safety and effectiveness of the Perceval S valve at 12 months after implantation when used to replace a diseased or dysfunctional aortic valve or aortic valve prosthesis.

Primary Endpoints

The primary endpoint of the clinical investigation is the evaluation of the safety and effectiveness of the Perceval S valve at 12 months after implant.

The safety of Perceval valve will be assessed in terms of percentage incidence of mortality and morbidity at 12 months after implant.

The effectiveness of the Perceval s valve will be assessed in terms of:

• Improvement of clinical status by mean of New York Heart Association (NYHA) functional class at 12 months after implant
• Haemodynamic performance through echocardiography parameters as mean gradient and peak gradient, effective orifice area (EOA), effective orifice area indexed (EOAI), performance index, cardiac output, cardiac index and degree of regurgitation at 12 months after implant

In order to determine mortality and morbidity, the following specific device related and procedure related adverse event categories will be assessed:

- valvular thrombosis, thromboembolism, hemorrhage (whether or not related to anti coagulant/ antiplatelet drug therapy) [all and major], paravalvular leak (all and major), endocarditis, hemolysis, structural valve deterioration, non structural dysfunction, reoperation (all and valve related), explant, death (all and valve related), device dislodgement and device migration

In order to assess the Haemodynamic performance the following echocardiography parameters will be measured:

- mean gradient and peak gradient, effective orifice area (EOA), effective orifice area indexed (EOAI), performance index, cardiac output, cardiac index and degree of regurgitation

Secondary Endpoints

The secondary endpoints of the clinical investigation are:

• Assessment of mortality and morbidity rates at discharge (or 30 days if the patient is still hospitalized) and at 3-6 months after implant
• Evaluation of the effectiveness of Perceval S valve in terms of improvement of clinical status assessed by means of NYHA functional class at discharge (or 30 days if the patient is still hospitalized), 3-6 months after surgery
• Evaluation of the effectiveness of Perceval S valve in terms of haemodynamic performance through echocardiography at discharge (or 30 days if the patient is still hospitalized) and 3-6 months after surgery
• Mortality and morbidity as well as haemodynamic parameters will be assessed

The Protocol has been amended (CAVALIER TPS001 Rev 4.0 Nov 17, 2017) to continue the follow up of a selection of implanted patients annually up to 10 years to evaluate long term device performance in the top enroller investigational sites.

The following secondary endpoints have been added:

• Assessment of mortality and morbidity rates annually until 10 years follow up. In order to determine mortality and morbidity, the following specific device related and procedure related adverse event categories will be assessed: valvular thrombosis, thromboembolism, hemorrhage (whether or not related to anti coagulant/ antiplatelet drug therapy) [all and major], paravalvular leak, endocarditis, hemolysis, structural valve deterioration, non structural dysfunction, reoperation, explant, death (all and valve related), device dislodgement and device migration.
• Evaluation of the effectiveness of Perceval valve in terms of improvement of clinical status assessed by NYHA change from baseline versus each follow-up up to 10 years.
• Evaluation of the effectiveness of Perceval valve in terms of haemodynamic performance through echocardiography at each follow up until 10 years. In order to assess the haemodynamic performance the following echocardiography parameters will be measured: mean gradient and peak gradient, effective orifice area (EOA), effective orifice area indexed (EOAI), performance index, cardiac output, cardiac index and degree of regurgitation.

Inclusion Criteria:

1. Subjects of age > 65 years;
2. Subjects with aortic valve stenosis or steno-insufficiency;
3. Subjects in which preoperative evaluation indicated the need for native or prosthetic aortic valve replacement with a biological prosthesis;
4. Subjects willing to sign the informed consent;
5. Subjects willing to undergo all medical follow-up, echocardiography examinations and laboratory tests planned for the Study

Exclusion Criteria:

1. Subjects involved in any other clinical study for drugs or devices;
2. Subjects with a previously implanted Perceval S prosthesis, within the clinical study, that requires replacement
3. Subjects with previous implantation of valve prostheses or annuloplasty ring not being replaced by the study valve
4. Subjects requiring simultaneous cardiac procedures, apart from septal myectomy and/or coronary by-pass
5. Subjects who require double or multiple valve replacement or repair in whom the mitral, tricuspid, or pulmonic valve would be replaced with a non-Perceval S valve or repaired
6. Subjects with aneurysmal dilation or dissection of the ascending aortic wall
7. Subjects needing non elective intervention
8. Subjects with active endocarditis
9. Subjects with active myocarditis
10. Subjects with congenital bicuspid aortic valve
11. Subjects with aortic root enlargement, where the ratio between the diameter of the sino-tubular junction and the annulus diameter, assessed by TTE, is > 1.3 (see Attachment 1 for reference)
12. Subjects with aortic root height (measured from aortic annulus to sino-tubular junction) ≥ 21 mm for size 21, ≥ 22.5 mm for size 23 and ≥ 24 mm for size 25, and ≥ 25 mm for size XL/27
13. Subjects with myocardial infarction < 90 days before the planned valve implant surgery
14. Subjects with known hypersensitivity to nickel alloys
15. The subject has a documented history of substance (drug or alcohol) abuse
16. The subject is a prison inmate, institutionalized, or is unable to give informed consent;
17. The subject has a major or progressive non-cardiac disease that, in the investigator's experience, results in a life expectancy shorter than 1 year, or the implant of the device produces an unacceptable increased risk to the patient
18. The subject is undergoing renal dialysis for chronic renal failure or has hyperparathyroidism
19. The subject has had an acute preoperative neurological deficit, myocardial infarction, or cardiac event that has not returned to baseline or stabilized ≥ 30 days prior to the planned valve implant surgery