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NCT Number: NCT06784440

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

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.

Recruiting

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Key information

Age range

Up to 44 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location status: Recruiting

Location contact

Luca Ragni, MD

CONTACT

[email protected]

0512149024

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Evaluation of circulating donor free DNA in the recipient's blood (Dd-cfDNA: donor-derived cell free DNA)

Genetic

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 outcomes

  1. Determination of plasma levels of circulating dd-cfDNA in the recipient's blood

    Time frame: 1 day

    The primary aim of this study is to determine whether plasma levels of circulating dd-cfDNA in the recipient's blood can be predictive of the presence of acute myocardial rejection with the same sensitivity as the gold standard represented by immunohistochemical analysis on biopsy specimen. The presence of acute myocardial rejection is defined in accordance with the 2004 ISHLT guidelines as a finding at endomyocardial biopsy of cellulomediated rejection (grade 2R or 3R) and/or humoral rejection (pAMR grade 1,2 or 3), while dd-cfDNA levels, expressed as a percentage relative to the recipient's DNA, will be assessed as pathological both based on the indications in the literature for other forms of rejection (>1%), and as a continuous scale to determine a possible specific cutoff value for our population.

Study contacts

Contact information is provided by the study sponsor or research team.

Luca Ragni, MD

CONTACT

[email protected]

0512149024

Sponsors and collaborators

Lead sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Other

Registry information

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
Jan 20, 2025
Registry last updated
Jan 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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