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TRANSLINK: Defining the Role of Xeno-directed and Immune Events (SVD) in Patients Receiving Animal-derived Bioprosthetic Heart Valves

Not Applicable
Completed
Conditions
Patients Receiving Animal-derived Bioprosthetic Heart Valves
Interventions
Device: Patients receiving animal-derived bioprosthetic heart valves.
Other: Echocardiography (3)
Other: Echocardiography (1)
Other: Echocardiography (2)
Biological: Blood sample (3)
Biological: Blood sample (1)
Biological: Blood sample (2)
Registration Number
NCT02023970
Lead Sponsor
Nantes University Hospital
Brief Summary

Cardiac valve disorders are widely spread in the general population and represents the third most frequent cardiovascular illness after coronary disease and arterial hypertension. In this context, aortic valve stenosis (the central pathology in this project) is the most common form of valve disease. Cardiac valve replacement is in the vast majority of cases the first line therapy for degenerative heart-valve diseases. These are represented by mechanical and bioprosthetic valve (BHV). In the vast majority of cases, BHV are derived from animals and from a biological standpoint are classified as xenografts. BHV are severely penalised by a premature structural damage, with ultimate valve failure occurring around 10 years after surgery in 5 to 30% of cases, depending on the type of BHV used. Several factors \[including dyslipidaemia, gender, valve position\] may contribute to the ultimate failure of the BHV and there has been increasing evidence recently of a substantial immune reaction elicited by the implanted BHV. This immune response is still poorly understood. It may lead to adverse immune reactions and this will be thoroughly investigated by the TRANSLINK team. In this light, the TRANSLINK project aims to provide the necessary data to demonstrate beyond any reasonable doubt the central role of the anti-BHV immune response in the premature failure of BHV and to provide efficient strategies to enable safe implantation of BHV valves in currently unsuitable candidates

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1668
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Phase B2 (Prospective Study): Cohort of incident patientsEchocardiography (3)Due to the low incidence of SVD during the first 4 post-operative years, a second cohort will be constituted by patients undergone biological aortic valve replacement at least 5 years before. The objective of this second cohort is to cover a period of time where risk of SVD occurrence is potentially high.
Phase A: Diagnostic StudyEchocardiography (1)Objective: to assess the differential immune response in patients with or without SVD (given the low rate of SVD) a matched cases-controls study allows a powerful statistical analysis avoiding main confounding factors for a first discovery of a SVD-specific immune response. Results will be validated in prospective Phase B.
Phase B2 (Prospective Study): Cohort of incident patientsPatients receiving animal-derived bioprosthetic heart valves.Due to the low incidence of SVD during the first 4 post-operative years, a second cohort will be constituted by patients undergone biological aortic valve replacement at least 5 years before. The objective of this second cohort is to cover a period of time where risk of SVD occurrence is potentially high.
Phase B1 (Prospective Study): Cohort of prevalent patientsPatients receiving animal-derived bioprosthetic heart valves.This cohort is specifically designed to study the kinetics of the immune response before and after implantation of an aortic BHV. Eight of the most frequently implanted BHV worldwide will be assessed:
Phase A: Diagnostic StudyPatients receiving animal-derived bioprosthetic heart valves.Objective: to assess the differential immune response in patients with or without SVD (given the low rate of SVD) a matched cases-controls study allows a powerful statistical analysis avoiding main confounding factors for a first discovery of a SVD-specific immune response. Results will be validated in prospective Phase B.
Phase B2 (Prospective Study): Cohort of incident patientsBlood sample (3)Due to the low incidence of SVD during the first 4 post-operative years, a second cohort will be constituted by patients undergone biological aortic valve replacement at least 5 years before. The objective of this second cohort is to cover a period of time where risk of SVD occurrence is potentially high.
Phase A: Diagnostic StudyBlood sample (1)Objective: to assess the differential immune response in patients with or without SVD (given the low rate of SVD) a matched cases-controls study allows a powerful statistical analysis avoiding main confounding factors for a first discovery of a SVD-specific immune response. Results will be validated in prospective Phase B.
Phase B1 (Prospective Study): Cohort of prevalent patientsEchocardiography (2)This cohort is specifically designed to study the kinetics of the immune response before and after implantation of an aortic BHV. Eight of the most frequently implanted BHV worldwide will be assessed:
Phase B1 (Prospective Study): Cohort of prevalent patientsBlood sample (2)This cohort is specifically designed to study the kinetics of the immune response before and after implantation of an aortic BHV. Eight of the most frequently implanted BHV worldwide will be assessed:
Primary Outcome Measures
NameTimeMethod
Echocardiography data to assess the structural valve deterioration5 years

The primary endpoint to be analyzed in the study is assessment by echocardiography of structural valve deterioration after implantation of pig valve or bovine pericardium valve or equine pericardium valve.

TRANSLINK project aims primarily at establishing the possible role of recipient immune response against biological prosthetic heart valves as a major cause to mid-long-term structural valve deterioration and clinical dysfunction.

Secondary Outcome Measures
NameTimeMethod
Process of valve degeneration according to the type of BHV5 years

To study the process of valve degeneration according to the type of BHV (porcine, bovine or equine BHV or type of industrial process) and BHV clinical outcome.

Large international and prospective patient's cohort and clinical database with a biocollection5 years

To implement a large international and prospective patient's cohort and clinical database with a biocollection (biobank) of patients receiving an aortic BHV to identify immune biomarkers following aortic valve replacement.

Clinic-biological correlations5 years

To analyse clinic-biological correlations prospectively following BHV.

Trial Locations

Locations (5)

University of Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

Nantes University Hospital

🇫🇷

Nantes, France

University of Padova Medical School, Italy

🇮🇹

Padova, Italy

University Hospital Vall d'Hebron, Barcelona, Spain

🇪🇸

Barcelona, Spain

University Hospital of Bellvitge, Barcelona, Spain

🇪🇸

Barcelona, Spain

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