Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection (FreeDNA-CAR)

Donor-derived Cell Free DNA as a Potential New Biomarker in Cardiac Transplantation: Role in Acute Rejection

FreeDNA-CAR is a prospective, observational multicenter study, that will include a total of 200 adult heart transplant (HT) patients from 14 centers in Spain. Our main objective is to test donor-derived Cell-Free DNA (dd-cfDNA) against endomyocardial biopsy (EMB) for the diagnosis of acute cellular rejection.

Study Overview

• Status: Recruiting
• Conditions: Heart Transplant Rejection
• Intervention / Treatment: Diagnostic test: Donor-derived cell Free DNA

Detailed Description

All patients will be enrolled immediately after HT, and will undergo undergo routine surveillance EMB at 15 days, 1 month, 2, 3, 4, 6 and 12 months after HT. Simultaneously with each EMB, dd-cfDNA will be measured in plasma.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Marta B Jimenez-Blanco Bravo, MD; Phone Number: 0034 637747916; Email: martajbb@gmail.com
• Study Contact Backup: Name: Javier Segovia Cubero, MD PhD; Email: jsecu@telefonica.net

Study Locations

• Spain
  • A Coruña, Spain
    • Recruiting
    • Hospital Universitario A Coruña
  • Barcelona, Spain
    • Recruiting
    • Hospital Clínic de Barcelona
  • Barcelona, Spain
    • Recruiting
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain
    • Recruiting
    • Hospital Bellvitge
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Gregorio Marañón
  • Madrid, Spain
    • Recruiting
    • Hospital 12 Octubre
  • Murcia, Spain
    • Recruiting
    • Hospital Virgen de la Arrixaca
  • Sevilla, Spain
    • Recruiting
    • Hospital Virgen del Rocio
  • Valencia, Spain
    • Recruiting
    • Hospital La Fe
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Recruiting
      • Hospital Universitario Central de Asturias
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • University Hospital Puerta de Hierro
      • Contact: Marta Jimenez-Blanco Bravo, MD; Phone Number: 0034637747916; Email: martajbb@gmail.com
      • Contact: Javier Segovia Cubero, MD PhD
  • Navarra
    • Pamplona, Navarra, Spain
      • Recruiting
      • Clinica Universitaria de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Heart transplant recipients aged 18 and over

Description

Inclusion Criteria:

• Patients > 18 years old who undergo heart transplant during the recruiting period

Exclusion Criteria:

• Patients with moderate or severe Primary Graft Dysfunction
• Patients on invasive mechanical ventilation 15 days after heart transplant
• Patients on renal replacement therapy, continuous or periodic, 15 days after heart transplant
• Heart Transplant due to a cardiomyopathy that could potentially recur on the graft (cardiac amyloidosis, Chagas disease or sarcoidosis, amongst others)
• Multiorgan transplant

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between dd-cfDNA levels and the presence of acute cellular rejection	Association between dd-cfDNA levels above a certain cut-point and the presence of treatable acute cellular rejection as determined by endomyocardial biopsy (graded by International Society of Heart and Lung Transplantation 2010 classification, grade > 1R).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under curve for dd-cfDNA	To define a cutt-off point of dd-cfDNA level with a high negative predictive value that could obviate the need to perform surveillance endomyocardial biopsies	1 year
Correlation between dd-cfDNA and antibody mediated rejection (AMR)	Correlation between dd-cfDNA and antibody mediated rejection (AMR)	1 year
Association between dd-cfDNA and immunosuppressive (IS) treatment	Subanalysis of association between dd-cfDNA and rejection stratified by IS regimen (type and dose of drug).	1 year
Association between dd-cfDNA (%) and left ventricular ejection fraction	Association between dd-cfDNA and left ventricular ejection fraction (LVEF). All echocardiograms will be performed on the same day of EMB.	1 year
Determine the biomarker's kinetics at 15 days post-transplant	Determine dd-cfDNA levels at 15 days post-transplant in absence of rejection	15 days
Association between dd-cfDNA levels and cytomegalovirus (CMV) infection	Association between dd-cfDNA levels and CMV infection as determined by CMV polymerase chain reaction (number of copies per ml)	1 year
Determine a cut-off point of dd-cfDNA that allows to differentiate between acute cellular rejection (ACR) and antibody mediated rejection (AMR)	Determine a cut-off point of dd-cfDNA that allows to differentiate between acute cellular rejection (ACR) and antibody mediated rejection (AMR)	1 year

Collaborators and Investigators

• Sponsor: Puerta de Hierro University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Acute cellular rejection; Donor-derived cell Free DNA
• Other Study ID Numbers: FreeDNA-CAR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No