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

NCT06784440 | Recruiting

• 2 other identifiers: PED-TRANSPLANT-DNARC2022
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Heart Disease (CHD); Heart Transplant Patients; Adult Congenital Heart Disease; Pediatric Congenital Heart Disease

Outcome Measures

Primary Outcomes (1)

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

  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.

  1 day

Study Arms (1)

Endomyocardial biopsy and analysis for the presence of dd-cfDNA

OTHER

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

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

Interventions

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.

Endomyocardial biopsy and analysis for the presence of dd-cfDNA

Eligibility Criteria

• Age: Up to 44 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

RECRUITING

MeSH Terms

Conditions

Heart Defects, Congenital

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Luca Ragni, MD

  IRCCS Azienda Ospedaliero-Universitaria di Bologna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luca Ragni, MD

CONTACT

0512149024; luca.ragni@aosp.bo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: January 20, 2025
• Study Start: March 8, 2023
• Primary Completion: November 8, 2025
• Study Completion: March 7, 2026
• Last Updated: January 20, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)