HAART 200 Aortic Valve Annuloplasty Trial

Study Overview
=================
Brief Summary
-----------------
The HAART 200 Aortic Annuloplasty during Bicuspid Aortic Valve Reconstruction Trial is a prospective, non-randomized, multi-center trial to evaluate the safety and effectiveness of the HAART 200 bicuspid annuloplasty ring when used to surgically stabilize the aortic valve annulus in patients undergoing repair of bicuspid aortic valves (BAV) for predominant aortic insufficiency (AI).

Detailed Description
-----------------
Aortic valve disease is the most common valvular heart disease with approximately 200,000 patients per year undergoing conventional aortic valve replacement in North America and Europe. Around 60% of valves have Aortic Stenosis (AS) and 40% of have Aortic Insufficiency, which is the failure of the aortic valve to close completely during diastole, causing blood to flow from the aorta back into the left ventricle. Bicuspid valve morphology is present in a fourth to a third of patients coming to surgical intervention, and constitutes a very important subset. Several conditions are associated with bicuspid disease, including ascending aortic or root aneurysms in up to a third. Traditional management of aortic valve and root disease has been with aortic valve replacement, with or without root replacement (Bentall Procedure). However, as has been observed in patients with mitral valve repair, the option of maintaining one's reconstructed native valve versus a replacement, either bioprosthetic or mechanical, can have multiple benefits. The advantages of repair include: the avoidance of prosthetic valve related complications and structural degeneration with bioprosthetic valves over 10-15 years and elimination of the need for anticoagulation and related problems with mechanical valves in younger patients. The significantly lower rate of endocarditis after repair is a major impetus to increasing performance of BAV reconstruction. Thus, aortic valve repair currently is established as an excellent option for patients with BAV. However, with connective tissue disorders being an inherent feature of BAV, outcomes have been less stable long-term than for trileaflet repair, primarily because of late annular redilatation in BAV disease. Therefore, this study is designed to evaluate the safety and effectiveness of annular stabilization with a bicuspid annuloplasty ring in patients undergoing repair of a bicuspid aortic valve for predominant aortic insufficiency.

Official Title
-----------------
HAART 200 Aortic Valve Annuloplasty During Bicuspid Aortic Valve Reconstruction Trial

Conditions
-----------------
Aortic Insufficiency

Intervention / Treatment
-----------------
* Device: HAART 200 Aortic Valve Annuloplasty Device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is 18 years of age or older The subject has bi-leaflet aortic valve morphology The subject has documented aortic valve disease which may or may not include: Aortic valve insufficiency Ascending aortic or aortic root pathology Other pathology of the ascending aorta that requires elective aortic replacement Associated stable one or two vessel coronary disease requiring concomitant coronary bypass Patients with recurrent severe AI (Grade 3 or 4) after prior bicuspid repair who are undergoing re-repair because of annular re-dilatation All bicuspid annular and leaflet configurations will be included The subject needs: correction of BAV annular dilatation in patients with chronic AI and dilated annulus restoration of a circular annular shape in patients with bicuspid valve and expansion of sinus to sinus dimensions stabilization of annular geometry long-term in rare bicuspid valve patients with severe AI and minimal annular dilatation The is willing to comply with specified follow-up evaluations, including transesophageal echocardiography (TEE) if there are inadequate images by transthoracic echocardiography (TTE) to assess the aortic valve The subject has reviewed and signed the written informed consent form The subject agrees to return for all follow-up evaluations for the duration of the study (i.e. geographically stable) Exclusion Criteria: All patients will be excluded who require emergency surgery for any reason. All the patients who have had a prior heart valve replacement The subject's aortic valve morphology is not bicuspid. The subject has active endocarditis The subject has mixed stenosis and regurgitation of the aortic valve with predominant stenosis Heavily calcified BAV valves, calcified aortic roots, or porcelain aortas Leukopenia with a White Blood Cell (WBC) of less than 3000 Acute anemia with a Hgb less than 9mg% Platelet count less than 100,000 cells/mm3 History of a defined bleeding diathesis or coagulopathy or the subject refuses blood transfusions Active infection requiring antibiotic therapy (if temporary illness, subjects may enroll 2-4 weeks after discontinuation of antibiotics) Subjects in whom transesophageal echocardiography (TEE) is contraindicated Low Ejection Fraction (EF) < 35% Life expectancy < 1 year, or severe comorbidities, such as dialysis or severe Chronic Obstructive Pulmonary Disease (COPD) The subject is or will be participating in a concomitant research study of an investigational product or has participated in such a study within the 30 days prior to screening The subject is a minor, an illicit drug user, alcohol abuser, prisoner, institutionalized, or is unable to give informed consent The subject is pregnant or lactating Recent (within 6 months) cerebrovascular accident (CVA) or a transient ischemic attack (TIA) Myocardial Infarction (MI) within one month of trial inclusion The subject has a known intolerance to titanium or polyester The subject has documented unstable or > 2 vessel coronary disease The subject requires additional valve replacement or valve repair

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aortic Valve Repair<br>Implantation of HAART 200 Aortic Valve Annuloplasty Device for bicuspid aortic valve reconstruction | Device: HAART 200 Aortic Valve Annuloplasty Device<br>* Surgical repair of bicuspid aortic valve using the HAART 200 Aortic Valve Annuloplasty Device .<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Outcome Measure: Survival Defined as Survival Free From All Cause Death at 6 Months Postprocedure. |  | 6 months postprocedure | 
| Primary Efficacy Outcome Measure: Aortic Insufficiency (AI) at 6 Months | Aortic insufficiency assessed by transthoracic echocardiography and graded as None/Trace (0), Mild (1+), Moderate (2+), Moderately Severe (3+), or Severe (4+) | 6 months postprocedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implant Procedure Success | Success is defined as the absence of specified adverse events evaluated through discharge following the procedure: - Aortic annular dissection, rupture, or leaflet damage - Mitral valve impingement due to implant - implant dehiscence/migration into aorta - implant dehiscence/migration into left ventricle - Hemodynamics requiring intervention - Other adverse event resulting in reoperation, explantation, or permanent disability. | discharge or 14 days postprocedure, whichever comes first | 
| Actuarial Freedom From Clinical Cardiovascular Events | Freedom from specified clinical cardiovascular events 6 months postprocedure: - Device-related mortality - Complete heart block - Structural device failure - Endocarditis - Periprosthetic leak or dehiscence - Thromboembolism - Bleeding Event - Native Valve Deterioration - Valve Thrombosis - Hemolysis - Reoperation and explant at 6 months | 6 months postprocedure | 
| Actuarial Freedom From Clinical Cardiovascular Events | Freedom from specified clinical cardiovascular events 6 months postprocedure: - Device-related mortality - Complete heart block - Structural device failure - Endocarditis - Periprosthetic leak or dehiscence - Thromboembolism - Bleeding Event - Native Valve Deterioration - Valve Thrombosis - Hemolysis - Reoperation and explant at 6 months | 2 years postprocedure | 
| Survival Defined as Survival Free From All Cause Death at 2 Years Postprocedure. |  | 2 years | 
| Aortic Insufficiency (AI) at 2 Years | Aortic insufficiency assessed by transthoracic echocardiography and graded as None/Trace (0), Mild (1+), Moderate (2+), Moderate-to-Severe (3+), or Severe (4+) | Baseline and 2 years | 
| New York Heart Association (NYHA) Functional Capacity Classification | Four classes describing the effect of cardiac disease on physical activity: Class I - disease does not limit activity; Class II - slight limitation; Class III - marked limitation; Class IV - inability to carry out any physical activity without discomfort | 6 months postprocedure | 
| NYHA Functional Capacity Classification | Four classes describing the effect of cardiac disease on physical activity: Class I - disease does not limit activity; Class II - slight limitation; Class III - marked limitation; Class IV - inability to carry out any physical activity without discomfort | 2 years postprocedure | 
| Peak Gradient - Change From Baseline | Transthoracic echocardiography parameter | Baseline and 6 months | 
| Peak Gradient - Change From Baseline | Transthoracic echocardiography parameter | Baseline and 2 years | 
| Mean Gradient - Change From Baseline | Transthoracic echocardiography parameter | Baseline and 6 months | 
| Mean Gradient - Change From Baseline | Transthoracic echocardiography parameter | Baseline and 2 years | 
| Left Ventricular (LV) Mass - Change From Baseline | Left ventricular mass. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| LV Mass - Change From Baseline | Left ventricular mass. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| Left Ventricular Internal Dimension (LVID) Diastole - Change From Baseline | Left ventricular internal dimension. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| LVID Diastole - Change From Baseline | Left ventricular internal dimension. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| LVID Systole - Change From Baseline | Left ventricular internal dimension. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| LVID Systole - Change From Baseline | Left ventricular internal dimension. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| LV Diastolic Volume - Change From Baseline | Left ventricular diastolic volume. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| LV Diastolic Volume - Change From Baseline | Left ventricular diastolic volume. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| LV Systolic Volume - Change From Baseline | Left ventricular systolic volume. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| LV Systolic Volume - Change From Baseline | Left ventricular systolic volume. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| Left Ventricular Ejection Fraction (LVEF) - Change From Baseline | Left ventricular ejection fraction. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| Left Ventricular Ejection Fraction (LVEF) - Change From Baseline | Left ventricular ejection fraction. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| Cardiac Output - Change From Baseline | Stroke volume x heart rate. Transthoracic echocardiography parameter. | Baseline and 6 months | 
| Cardiac Output - Change From Baseline | Stroke volume x heart rate. Transthoracic echocardiography parameter. | Baseline and 2 years | 
| Cardiac Index - Change From Baseline | Hemodynamic parameter computed as cardiac output divided by body surface area | Baseline and 6 months | 
| Cardiac Index - Change From Baseline | Hemodynamic parameter computed as cardiac output divided by body surface area | Baseline and 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aortic Insufficiency, Aortic Regurgitation