Heart Transplant Rejection
Conditions
Keywords
Donor-derived cell Free DNA, Acute cellular rejection
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTDonor-derived cell Free DNA
Measurement of dd-cfDNA and comparison against grade of rejection as determined by endomyocardial biopsy, taken simultaneously
Sponsors
Puerta de Hierro University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Association between dd-cfDNA levels and the presence of acute cellular rejection | 1 year | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between dd-cfDNA and antibody mediated rejection (AMR) | 1 year | Correlation between dd-cfDNA and antibody mediated rejection (AMR) |
| Association between dd-cfDNA and immunosuppressive (IS) treatment | 1 year | Subanalysis of association between dd-cfDNA and rejection stratified by IS regimen (type and dose of drug). |
| Association between dd-cfDNA (%) and left ventricular ejection fraction | 1 year | Association between dd-cfDNA and left ventricular ejection fraction (LVEF). All echocardiograms will be performed on the same day of EMB. |
| Area under curve for dd-cfDNA | 1 year | 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 |
| Association between dd-cfDNA levels and cytomegalovirus (CMV) infection | 1 year | Association between dd-cfDNA levels and CMV infection as determined by CMV polymerase chain reaction (number of copies per ml) |
| Determine a cut-off point of dd-cfDNA that allows to differentiate between acute cellular rejection (ACR) and antibody mediated rejection (AMR) | 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 the biomarker's kinetics at 15 days post-transplant | 15 days | Determine dd-cfDNA levels at 15 days post-transplant in absence of rejection |
Countries
Spain
Contacts
Primary ContactMarta B Jimenez-Blanco Bravo, MD
Backup ContactJavier Segovia Cubero, MD PhD
Outcome results
None listed