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

NCT02023970 | Completed

• 1 other identifier: RC13_0241
• Study Type: interventional
• Target: 1,668
• Locations: 4 countries
• Sites: 5

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

Conditions

Patients Receiving Animal-derived Bioprosthetic Heart Valves

Keywords

Bioprosthetic heart valves, immune response, structural valve deterioration, valvular disease

Outcome Measures

Primary Outcomes (1)

• Echocardiography data to assess the structural valve deterioration

  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.

  5 years

Secondary Outcomes (3)

• Process of valve degeneration according to the type of BHV

  5 years

• Large international and prospective patient's cohort and clinical database with a biocollection

  5 years

• Clinic-biological correlations

  5 years

Study Arms (3)

Phase A: Diagnostic Study

OTHER

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); Biological: Blood sample (1)

Phase B1 (Prospective Study): Cohort of prevalent patients

OTHER

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); Biological: Blood sample (2)

Phase B2 (Prospective Study): Cohort of incident patients

OTHER

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); Biological: Blood sample (3)

Interventions

Patients receiving animal-derived bioprosthetic heart valves. DEVICE

Phase A: Diagnostic Study; Phase B1 (Prospective Study): Cohort of prevalent patients; Phase B2 (Prospective Study): Cohort of incident patients

Echocardiography (1) OTHER

Also known as: Echocardiography at the baseline (inclusion visit)

Phase A: Diagnostic Study

Echocardiography (2) OTHER

Also known as: Echocardiography will be performed at visits before surgery, 6, 24 and 42 months at inclusion site.

Phase B1 (Prospective Study): Cohort of prevalent patients

Echocardiography (3) OTHER

Also known as: 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.

Phase B2 (Prospective Study): Cohort of incident patients

Blood sample (1) BIOLOGICAL

Also known as: Blood sample will be collected at the time of SVD diagnosis in SVD patients and non -SVD control patients.

Phase A: Diagnostic Study

Blood sample (2) BIOLOGICAL

Also known as: 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 B1 (Prospective Study): Cohort of prevalent patients

Blood sample (3) BIOLOGICAL

Also known as: 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.

Phase B2 (Prospective Study): Cohort of incident patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be enrolled, the following criteria have to be fulfilled:
• \*Phase A: Diagnostic Study
• 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, Bental, Mitral or Tricuspid repair, aortic surgery, Radiofrequency.
• First cardiac surgery (no multiple cardiac surgeries)
• No immunosuppressive regimen any time within the 6 months prior surgery.
• \- No use of other allo or xenogenic tissue than aortic valve prosthesis during cardiac surgery
• 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
• 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.

You may not qualify if:

• 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
• Active autoimmune disease
• Multiple cardiac surgeries
• Patient with immunosuppression regimen
• 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
• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (5)

University of Manitoba

Winnipeg, Manitoba, Canada

Location

Nantes University Hospital

Nantes, France

Location

University of Padova Medical School, Italy

Padua, Italy

Location

University Hospital of Bellvitge, Barcelona, Spain

Barcelona, Spain

Location

University Hospital Vall d'Hebron, Barcelona, Spain

Barcelona, Spain

Location

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jean-christian ROUSSEL, Professor

  Nantes University Hospital

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 30, 2013
• Study Start: January 6, 2014
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: November 2, 2020

Record last verified: 2020-10

Locations

IT (1); CA (1); FR (1); ES (2)