Clinical trial NCT06740578: Evaluation of the Added Clinical Value of Donor-derived Cell-free DNA for the Monitoring of Cardiac Allograft Rejection.
Official title: Evaluation of the Added Clinical Value of Donor-derived Cell-free DNA for the Monitoring of Cardiac Allograft Rejection: an Observational Prospective Longitudinal Multicenter Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Transplantation
Rejection Heart Transplant
Keywords: heart transplantation
donor-derived cell-free DNA
non-invasive biomarker
allograft rejection
risk stratification
Lead sponsor: Paris Translational Research Center for Organ Transplantation
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Prospective cohort of heart transplant recipients (\> 30 days post-transplant)

Brief summary: The goal of this observational study is to assess the clinical added value of donor-derived cell-free DNA (dd-cfDNA) to monitor cardiac allograft rejection. The main question it aims to answer is whether dd-cfDNA is independently associated with rejection and if it allows a significant improvement in individual risk stratification of rejection on top of a robust predictive model based on standard clinical and biological predictive variables.

Detailed description: Despite major advances in immunosuppression, allograft rejection remains an important complication after heart transplantation. International guidelines recommend performing routine endomyocardial biopsies (EMB) to detect allograft rejection with the goal of identifying rejection at a subclinical state. However, this invasive strategy suffers from major limitations, making an improvement in individual risk stratification of rejection highly needed. Major advances in the field of non-invasive biomarkers of cardiac rejection have been made. Strong associations between donor-derived cell-free DNA (dd-cfDNA) and cardiac rejection have been reported, including in properly designed prospective observational studies with a longitudinal follow-up. However, the independent nature of this association and the improvement in individual risk stratification with dd-cfDNA on top of routine parameters have not yet been demonstrated. The aim of our study is to challenge, in a large observational prospective cohort, the clinical added value of dd-cfDNA with a previously published robust rejection predictive model including the following variables: time post-transplant, pre-transplant sensitizing event, circulating anti-HLA donor-specific antibodies (DSA) with mean fluorescence intensity ≥ 3,000, acute graft dysfunction and prior history of rejection.

Eligibility criteria: Inclusion Criteria:

* heart transplant recipients,
* heart transplantation performed for more than 30 days,
* clinical indication of an endomyocardial biopsy, either protocol or for cause,
* informed consent

Exclusion Criteria:

* multiorgan transplantation
* refusal to participate

Primary outcomes:
measure: Number of patients with biopsy proven rejection and / or acute allograft dysfunction
timeFrame: 12 months
Secondary outcomes:
measure: Independent association between donor-derived cell-free DNA and allograft ejection
timeFrame: 12 months
measure: Individual risk stratification
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
city: Paris
country: France
facility: Georges Pompidou European Hospital
Study officials:
References:
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