Aortic Stenosis, Aortic Valve Disease
Conditions
Keywords
Sutureless valve
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.
Interventions
DEVICEPerceval valve
Sutureless Aortic Biological Valve
DEVICEother stented biological valve
Any biological stented valves available on the market (Edwards, Medtronic, St.Jude, LivaNova, Labcor)
Sponsors
Corcym S.r.l
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject has an indication for treatment by valve replacement with a bioprosthesis according to the IFU, through either full sternotomy or mini-sternotomy. 2. The subject has aortic valve disease that can be treated with a commercially available Perceval valve size, based on preoperative CT-scan. 3. The subject has: 1. 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 2. 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; 4. The subject is symptomatic due to aortic stenosis with functional class of New York Heart Association (NYHA) II or higher. 5. The subject has signed the informed consent. 6. The subject is of legal minimum age. 7. The subject will be available for postoperative follow-up beyond one year.
Exclusion criteria
1. The subject has a contraindication for treatment by the Perceval valve or by a bioprosthetic aortic valve as stated in the IFU. 2. The subject has aneurismal dilation or dissection of the ascending aortic wall. 3. The subject is scheduled for concomitant procedures other than Coronary Aortic Bypass Graft (CABG), myectomy with or without aortic annulus enlargement 4. The subject has congenital bicuspid (i.e. Sievers type 0) or unicuspid aortic valve. 5. 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. 6. The subject has a prosthetic heart valve in any position, including mitral valve repair. 7. The subject has a stroke or myocardial infarction (STEMI and NSTEMI) within 30 days prior to the planned valve implant surgery. 8. The subject has active endocarditis, myocarditis, or sepsis. 9. The subject is in cardiogenic shock manifested by low cardiac output and needing hemodynamic support. 10. The subject is allergic to nickel alloys. 11. The subject is already included in another clinical trial that could confound the results of this clinical investigation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Freedom From Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 1 year post-operatively | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgical Times | Intra-operative | 1. Cross clamp time during index procedure 2. 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 |
Countries
Austria, Belgium, Canada, Chile, France, Germany, Israel, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 914 patients were enrolled in the PERSIST-AVR trial. Among the 914 patients enrolled, 910 underwent randomization
Pre-assignment details
A total of 914 patients were enrolled in the PERSIST-AVR trial. Among the 914 patients enrolled, 910 underwent randomization. 4 patients were not randomized due to consent withdrawal (2 cases) and physician decision (2 cases)
Participants by arm
| Arm | Count |
|---|---|
| Perceval 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.
Perceval valve: Sutureless Aortic Biological Valve | 407 |
| Other Stented Biological Valves 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.
other stented biological valve: Any biological stented valves available on the market (Edwards, Medtronic, St.Jude, LivaNova, Labcor) | 412 |
| Total | 819 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Change subj medical status | 1 | 2 |
| Overall Study | Death | 32 | 24 |
| Overall Study | Explant | 10 | 5 |
| Overall Study | Lost to Follow-up | 5 | 2 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Sponsor Decision to stop follow up | 391 | 416 |
| Overall Study | Withdrawal by Subject | 10 | 7 |
Baseline characteristics
| Characteristic | Perceval | Other Stented Biological Valves | Total |
|---|---|---|---|
| Age, Continuous | 75.4 years STANDARD_DEVIATION 5.6 | 75.0 years STANDARD_DEVIATION 6.1 | 75.2 years STANDARD_DEVIATION 5.9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 204 Participants | 185 Participants | 389 Participants |
| Sex: Female, Male Male | 203 Participants | 227 Participants | 430 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 450 | 24 / 446 |
| other Total, other adverse events | 0 / 450 | 0 / 446 |
| serious Total, serious adverse events | 390 / 450 | 342 / 446 |
Outcome results
Primary
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.
Time frame: 1 year post-operatively
Population: Per Protocol Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Perceval | Proportion of Participants With Freedom From Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 0.917 Proportion of participants |
| Other Stented Biological Valves | Proportion of Participants With Freedom From Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 0.920 Proportion of participants |
Comparison: A the primary analysis will compare Perceval valve (Treatment arm) vs. standard sutured stented valve (Control arm) on the Per Protocol population.~A one-sided non-inferiority test, using the non-inferiority margin Δ=0.05, will be performed to compare the two arms on the proportion of subjects that are event-free at one year (primary analysis).p-value: 0.9914Bayesian
Secondary
Surgical Times
1. Cross clamp time during index procedure 2. 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
Time frame: Intra-operative
Population: Safety population (actual treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Perceval | Surgical Times | Cardiopulmonary bypass time | 71.0 Minutes | Standard Deviation 34.1 |
| Perceval | Surgical Times | Cross clamp time | 48.5 Minutes | Standard Deviation 24.7 |
| Other Stented Biological Valves | Surgical Times | Cardiopulmonary bypass time | 87.8 Minutes | Standard Deviation 33.9 |
| Other Stented Biological Valves | Surgical Times | Cross clamp time | 65.2 Minutes | Standard Deviation 23.6 |