Heart Transplant RejectionFreeDNA-CARNCT04973943
Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection
An observational study of Heart Transplant Rejection, run by Puerta de Hierro University Hospital at 12 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplant Rejection
- What is being tested?
- Donor-derived cell Free DNA
- How many people
- 200 participants
- Where
- 12 sitesSpain
- Study dates
- 19 Mar 2019to Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Heart transplant recipients aged 18 and over
Who may be able to join
- Patients > 18 years old who undergo heart transplant during the recruiting period
Who cannot join
- 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
Trial locations and contacts
12 sites in 1 country.
Javier Segovia Cubero, MD PhD contact
12 sites in 1 country
Spain12 sites, 12 recruiting
- Recruiting
Hospital Universitario A Coruña
A Coruña
- Recruiting
Hospital Bellvitge
Barcelona
- Recruiting
Hospital Clinic de Barcelona
Barcelona
- Recruiting
Hospital Santa Creu i Sant Pau
Barcelona
- Recruiting
Hospital 12 octubre
Madrid
- Recruiting
Hospital Universitario Gregorio Marañón
Madrid
- Recruiting
University Hospital Puerta de Hierro
Majadahonda, Madrid, 28222
Marta Jimenez-Blanco Bravo, MD, 0034637747916, martajbb@gmail.com
Javier Segovia Cubero, MD PhD
- Recruiting
Hospital Virgen de la Arrixaca
Murcia
- Recruiting
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
- Recruiting
Clinica Universitaria de Navarra
Pamplona, Navarre
- Recruiting
Hospital Virgen del Rocio
Seville
- Recruiting
Hospital La Fe
Valencia
About this study
Official title: Donor-derived Cell Free DNA as a Potential New Biomarker in Cardiac Transplantation: Role in Acute Rejection
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.
Read the detailed description
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.
- Conditions
- Heart Transplant Rejection
- Being tested
- Donor-derived cell Free DNA
- Keywords
- Donor-derived cell Free DNA, Acute cellular rejection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor-derived cell Free DNADiagnostic test
Measurement of dd-cfDNA and comparison against grade of rejection as determined by endomyocardial biopsy, taken simultaneously
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 year
Secondary outcomes (7)
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
Measured: 1 year
Correlation between dd-cfDNA and antibody mediated rejection (AMR)
Correlation between dd-cfDNA and antibody mediated rejection (AMR)
Measured: 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).
Measured: 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.
Measured: 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
Measured: 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)
Measured: 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)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2021
- Study start19 Mar 2019
- Primary completionApr 2022 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Puerta de Hierro University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Javier Segovia Cubero, Puerta de Hierro University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04973943
- Sponsor's protocol ID
- FreeDNA-CAR
- Acronym
- FreeDNA-CAR
- Status last verified
- Jul 2021
- First submitted
- 15 Mar 2021
- Last updated
- 22 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Jimenez-Blanco M, Crespo-Leiro MG, Garcia-Cosio Carmena MD, Gomez Bueno M, Lopez-Vilella R, Ortiz-Bautista C, Farrero-Torres M, Zegri-Reiriz I, Diaz-Molina B, Garcia-Romero E, Rangel-Sousa D, Salterain N, Garrido Bravo I, Segovia-Cubero J. Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR). J Heart Lung Transplant. 2025 Apr;44(4):560-569. doi: 10.1016/j.healun.2024.11.009. Epub 2024 Nov 20.
PubMed 39577511
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donor-derived Cell Free DNA as a Potential New Biomarker in Cardiac Transplantation: Role in Acute Rejection
- ClinicalTrials.gov ID
- NCT04973943
- Acronym / sponsor ID
- FreeDNA-CAR / FreeDNA-CAR
- Conditions
- Heart Transplant Rejection
- Keywords
- Donor-derived cell Free DNA, Acute cellular rejection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Puerta de Hierro University HospitalUniversity, hospital or other
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 22 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Heart transplant recipients aged 18 and over
Key inclusion criteria (1 listed)
- Patients > 18 years old who undergo heart transplant during the recruiting period
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Donor-derived cell Free DNAMeasurement of dd-cfDNA and comparison against grade of rejection as determined by endomyocardial biopsy, taken simultaneously | Diagnostic test | – |
Primary outcome
Association between dd-cfDNA levels and the presence of acute cellular rejection
Time frame: 1 year
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).
7 secondary outcomes
Area under curve for dd-cfDNA
Time frame: 1 year
Correlation between dd-cfDNA and antibody mediated rejection (AMR)
Time frame: 1 year
Association between dd-cfDNA and immunosuppressive (IS) treatment
Time frame: 1 year
Association between dd-cfDNA (%) and left ventricular ejection fraction
Time frame: 1 year
Determine the biomarker's kinetics at 15 days post-transplant
Time frame: 15 days
Association between dd-cfDNA levels and cytomegalovirus (CMV) infection
Time frame: 1 year
Determine a cut-off point of dd-cfDNA that allows to differentiate between acute cellular rejection (ACR) and antibody mediated rejection (AMR)
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2021.
- Derived from this study: PubMed 39577511Jimenez-Blanco M, Crespo-Leiro MG, Garcia-Cosio Carmena MD, Gomez Bueno M, Lopez-Vilella R, Ortiz-Bautista C, Farrero-Torres M, Zegri-Reiriz I, Diaz-Molina B, Garcia-Romero E, Rangel-Sousa D, Salterain N, Garrido Bravo I, Segovia-Cubero J. Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR). J Heart Lung Transplant. 2025 Apr;44(4):560-569. doi: 10.1016/j.healun.2024.11.009. Epub 2024 Nov 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javier Segovia Cubero, MD PhD contact
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplant Rejection, run by Puerta de Hierro University Hospital at 12 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marta B Jimenez-Blanco Bravo, MD (0034 637747916, martajbb@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between dd-cfDNA levels and the presence of acute cellular rejection (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04973943, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2021.