Search for Noninvasive Markers of "Graft Injury" in Pediatric and Adult Patients With Congenital Heart Disease Undergoing Cardiac Transplantation

Overview

This clinical tissue-based, drug-free, single-center, longitudinal study aims to validate a new diagnostic method, namely, to evaluate whether plasma levels of circulating donor free DNA in the recipient's blood (Dd-cfDNA: donor-derived cell free DNA), in patients undergoing orthotopic heart transplantation, can be predictive of the presence of acute myocardial rejection with the same sensitivity as immunohistochemical analysis on endomyocardial biopsy specimen, the current gold standard for the diagnosis of acute cell-mediated myocardial rejection, in a population consisting of pediatric patients and adult patients with congenital heart disease undergoing orthotopic heart transplantation.

Detailed description

To achieve the study objective, approximately 20 patients of all ages, both pediatric and adult with congenital heart disease and undergoing orthotopic heart transplantation, followed at our center will be enrolled. Whenever a patient enrolled in the study undergoes endomyocardial biopsy, either as part of surveillance of acute myocardial rejection or for clinical suspicion of rejection, concomitantly a blood sample will be taken and analyzed for the presence of dd-cfDNA. In patients with biopsy evidence of acute rejection, a new dd-cfDNA sampling will be performed approximately three months after treatment at the next clinical follow-up. The data collected for each patient will be both baseline anthropometric data and imaging and laboratory variables collected in the normal follow-up provided by clinical practice, as well as data related to the endomyocardial biopsy result and those related to blood sampling for donor DNA.

Interventions

• Genetic Evaluation of circulating donor free DNA in the recipient's blood (Dd-cfDNA: donor-derived cell free DNA)
  From the blood samples taken, 2 mL of plasma separated from blood will be stored in EDTA frozen at -80°C. This material will later be processed by NGS run using of CareDX kits. The result will be provided by dedicated software as percentage of donor DNA in relation to recipient DNA.

Primary outcome measures

• Determination of plasma levels of circulating dd-cfDNA in the recipient's blood [Time frame: 1 day]

Eligibility criteria

Inclusion criteria

• Adult patients with congenital heart disease undergoing cardiac transplantation at our center or other centers, followed in follow-up at our center (Unit of Pediatric Cardiology and Developmental Age, IRCCS Azienda Ospedaliero-Universitaria di Bologna)
• Pediatric patients undergoing cardiac transplantation at our center or other centers but followed in follow-up at our center
• Obtaining informed consent from the adult patient or parent/guardian in case of minor

Exclusion criteria

• Failure to obtain informed consent from the adult patient or parent/guardian in case of minor

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna

Identifiers

NCT: NCT06784440 · PED-TRANSPLANT-DNA · RC2022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗