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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Nantes University Hospital
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT02023970
First received: December 5, 2013
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention
Patients Receiving Animal-derived Bioprosthetic Heart Valves.
Device: Patients receiving animal-derived bioprosthetic heart valves.
Other: Echocardiography (1)
Other: Echocardiography (2)
Other: Echocardiography (3)
Biological: Blood sample (1)
Biological: Blood sample (2)
Biological: Blood sample (3)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: TRANSLINK: A Prospective, Multi-center, Multi-national, Non Randomized, Open, Study to Defining the Role of Xeno-directed and Immune Events (SVD) in Patients Receiving Animal-derived Bioprosthetic Heart Valves.

Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Echocardiography data to assess the structural valve deterioration [ Time Frame: 5 years ] [ Designated as safety issue: No ]

    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:
  • Process of valve degeneration according to the type of BHV [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 biocollection [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 correlations [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To analyse clinic-biological correlations prospectively following BHV.


Estimated Enrollment: 2925
Study Start Date: October 2013
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Phase A: Diagnostic Study
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.
Device: Patients receiving animal-derived bioprosthetic heart valves. Other: Echocardiography (1)
Other Name: Echocardiography at the baseline (inclusion visit)
Biological: Blood sample (1)
Other Name: Blood sample will be collected at the time of SVD diagnosis in SVD patients and non -SVD control patients.
Phase B1 (Prospective Study): Cohort of prevalent patients
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:
Device: Patients receiving animal-derived bioprosthetic heart valves. Other: Echocardiography (2)
Other Name: Echocardiography will be performed at visits before surgery, 6, 24 and 42 months at inclusion site.
Biological: Blood sample (2)
Other Name: Blood samples will be harvested the day before the surgery and then at 1, 6, 12, 24 and 42 months, representing 6 samples per patient.
Phase B2 (Prospective Study): Cohort of incident patients
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.
Device: Patients receiving animal-derived bioprosthetic heart valves. Other: Echocardiography (3)
Other Names:
  • At inclusion visit and:
  • - If normal echocardiographic parameters (without SVD signs): echocardiography at 42 months.
  • - If subnormal echocardiographic parameters (SVD signs): echocardiographic follow-up will be performed on site at 1 year and 42 months.
Biological: Blood sample (3)
Other Names:
  • At inclusion visit and:
  • - If normal echocardiographic parameters (without SVD signs): blood samples at 2 year and 42 months
  • - If subnormal echocardiographic parameters (SVD signs): blood samples at 1 year and 42 months.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

Phase A: Diagnostic Study

Inclusion criteria for SVD-patients:

  • Patient age: 18 to 85 years old at the time of surgery
  • Echographic signs of SVD (Mean trans-valvular gradient ≥ 30 mm Hg AND Effective Orifice Area ≤ 1 cm2 worsen over time OR Aortic Insufficiency > grade 2/4)
  • Single aortic valve replacement +/- associated to CABG
  • No immunosuppression regimen
  • No use of bovine pericardium
  • Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
  • Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site

Inclusion criteria for Non-SVD patients (control-patients):

  • Patients will be defined as patients operated on with an aortic BHV without echographic signs of SVD and matched for: Age at surgery (±2 years), , , type of BHV and follow-up time (± 6 months).
  • Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
  • Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site

To increase the statistical power (which cannot be calculated according to the novelty of the project), two controls will be matches with each SVD-Case.

Phase B: Prospective Study

B1: Cohort of prevalent patients

  • Patient age: 18 - 85 years old at the time of surgery
  • Patient scheduled for aortic valve replacement with a BHV (surgical or percutaneous valve) +/- associated to CABG
  • No immunosuppressive regimen prior and after surgery
  • No use of bovine pericardium.
  • Patient is affiliated to the Social Security or equivalent system
  • Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
  • Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site Eight of the most frequently implanted BHV worldwide will be assessed: 1 surgical porcine valve: Mosaic (Medtronic); 4 surgical bovine pericardium valves: Perimount-Carpentier (Edwards), Magna ease (Edwards), Trifecta (St. Jude Medical) and the Mitroflow PRT valve (Sorin); 1 surgical equine valve: 3F-valve or Enable (Medtronic) and 2 percutaneous pericardium valves (TAVI): Corevalve (porcine pericardium - Medtronic) and Sapien valve (bovine pericardium - Edwards).

Fifty patients per type of BHV will be included. When 50 patients were included in one of the eight groups, we will stop the inclusions in this group.

Additionally, a control group of heart operated patients without biological valve will be included in the study (patients operated on with a mechanical valve (n=50) or for CABG without BHV (n=50).

Control group (CABG or aortic mechanical valve)

  • Patient age: >65 years old for CABG and 18-85 years old for mechanical valve replacement
  • Patient operated on coronary artery bypass (for CABG group)
  • Patient with valve aortic replacement following aortic valve stenosis (for mechanical valve group)
  • No immunosuppressive regimen prior and after surgery
  • No use of bovine pericardium.

B2: Cohort of incident patients

  • Patient age: 18 to 85 years old who underwent a single isolated aortic valve replacement with a BHV (with or without coronary graft bypass) more than 5 years ago.
  • No immunosuppressive regimen prior and after surgery
  • Patient is affiliated to the Social Security or equivalent system
  • Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
  • Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site

As control, patients who underwent isolated CABG (n=50) or aortic mechanical valve replacement more than 5 years ago (n=50) will be enrolled.

Control group (CABG or aortic mechanical valve)

  • Patient age: > 65 years old for CABG and 18-85 years old for mechanical valve replacement
  • Patient operated on coronary artery bypass (for CABG group)
  • Patient with valve aortic replacement following aortic valve stenosis (for mechanical valve group)
  • No immunosuppressive regimen prior and after surgery
  • No use of bovine pericardium.

EXCLUSION CRITERIA

  • Female of child bearing potential
  • Severe renal insufficiency: GFR <=30 ml/min/
  • Severe dyslipidemia: total cholesterol >350 mg/dl, triglycerides >750 mg/dl
  • Ongoing infection (patient may be evaluated for enrolment after resolution)
  • HIV infection
  • Patient with immunosuppression regimen
  • Presence of any condition (psychological, social, or geographical), actual or anticipated, that the Investigator feels would restrict or limit the patient's successful participation for the duration of the study
  • Presence of any severe medical condition such that the patient is not expected to survive for the planned study follow-up period.
  • Patient is not able to give informed consent
  • Patient under trusteeship or under guardianship
  • Patient with no affiliation to a social security or equivalent system
  • Patient is currently participating in an investigational drug or device study that clinically interferes with the current study endpoints
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02023970

Contacts
Contact: Jean-Christian ROUSSEL, Professor +33 2 40 16 50 84 jean-christian.roussel@chu-nantes.fr

Locations
France
Nantes University Hospital Recruiting
Nantes, France
Italy
University of Padova Medical School, Italy Not yet recruiting
Padova, Italy
Spain
University Hospital of Bellvitge, Barcelona, Spain Not yet recruiting
Barcelona, Spain
University Hospital Vall d'Hebron, Barcelona, Spain Not yet recruiting
Barcelona, Spain
Sponsors and Collaborators
Nantes University Hospital
Investigators
Study Chair: Jean-christian ROUSSEL, Professor Nantes University Hospital
Principal Investigator: Gino GEROSA, Professor University of Padova Medical School, Italy
Principal Investigator: Rafael MAÑEZ, Professor University Hospital of Bellvitge, Barcelona, Spain
Principal Investigator: Manuel GALIÑANES, Professor University Hospital Vall d'Hebron, Barcelona, Spain
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02023970     History of Changes
Other Study ID Numbers: RC13_0241
Study First Received: December 5, 2013
Last Updated: December 23, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Nantes University Hospital:
Bioprosthetic heart valves, immune response, structural valve deterioration, valvular disease.

ClinicalTrials.gov processed this record on August 27, 2014