Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection

Heart Transplant Rejection Clinical Trial

— FreeDNA-CAR  

Official title:

Donor-derived Cell Free DNA as a Potential New Biomarker in Cardiac Transplantation: Role in Acute Rejection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04973943
• Other study ID #: FreeDNA-CAR
• Status: Recruiting
• Start date: March 19, 2019
• Est. completion date: April 2022

Study information

• Verified date: July 2021
• Source: Puerta de Hierro University Hospital
• Contact: Marta B Jimenez-Blanco Bravo, MD
• Phone: 0034 637747916
• Email: martajbb[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients > 18 years old who undergo heart transplant during the recruiting period

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Heart Transplant Rejection

Intervention

Diagnostic Test:
• Donor-derived cell Free DNA
Measurement of dd-cfDNA and comparison against grade of rejection as determined by endomyocardial biopsy, taken simultaneously

Locations

Country	Name	City	State
Spain	Hospital Universitario A Coruña	A Coruña
Spain	Hospital Bellvitge	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital 12 octubre	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	University Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Puerta de Hierro University Hospital

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	1 year
Secondary	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	1 year
Secondary	Correlation between dd-cfDNA and antibody mediated rejection (AMR)	Correlation between dd-cfDNA and antibody mediated rejection (AMR)	1 year
Secondary	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).	1 year
Secondary	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.	1 year
Secondary	Determine the biomarker's kinetics at 15 days post-transplant	Determine dd-cfDNA levels at 15 days post-transplant in absence of rejection	15 days
Secondary	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)	1 year
Secondary	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)	1 year