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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Donor-derived cell Free DNA | Diagnostic Test | Measurement of dd-cfDNA and comparison against grade of rejection as determined by endomyocardial biopsy, taken simultaneously |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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Heart transplant recipients aged 18 and over
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marta B Jimenez-Blanco Bravo, MD | Contact | 0034 637747916 | martajbb@gmail.com | |
| Javier Segovia Cubero, MD PhD | Contact | jsecu@telefonica.net |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Puerta de Hierro | Recruiting | Majadahonda | Madrid | 28222 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39577511 | Derived | Jimenez-Blanco M, Crespo-Leiro MG, Garcia-Cosio Carmena MD, Gomez Bueno M, Lopez-Vilella R, Ortiz-Bautista C, Farrero-Torres M, Zegri-Reiriz I, Diaz-Molina B, Garcia-Romero E, Rangel-Sousa D, Salterain N, Garrido Bravo I, Segovia-Cubero J. Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR). J Heart Lung Transplant. 2025 Apr;44(4):560-569. doi: 10.1016/j.healun.2024.11.009. Epub 2024 Nov 20. |
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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 |
| Clinica Universitaria de Navarra | Recruiting | Pamplona | Navarre | Spain |
| Hospital Universitario Central de Asturias | Recruiting | Oviedo | Principality of Asturias | 33011 | Spain |
| Hospital Universitario A Coruña | Recruiting | A Coruña | Spain |
| Hospital Bellvitge | Recruiting | Barcelona | Spain |
| Hospital Clinic de Barcelona | Recruiting | Barcelona | Spain |
| Hospital Santa Creu i Sant Pau | Recruiting | Barcelona | Spain |
| Hospital 12 octubre | Recruiting | Madrid | Spain |
| Hospital Universitario Gregorio Marañón | Recruiting | Madrid | Spain |
| Hospital Virgen de la Arrixaca | Recruiting | Murcia | Spain |
| Hospital Virgen del Rocio | Recruiting | Seville | Spain |
| Hospital La Fe | Recruiting | Valencia | Spain |