Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Heart Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Donor-derived cell Free DNA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Donor-derived cell Free DNA|Measurement of dd-cfDNA and comparison against grade of rejection as determined by endomyocardial biopsy, taken simultaneously|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donor-derived cell Free DNA, Acute cellular rejection