Donor Derived Cell Free DNA (Dd-cfDNA) as a Biomarker for Allograft Rejection in Heart Transplant Recipients

NCT07886489 | Enrolling By Invitation

• 1 other identifier: 1-10-72-67-25
• Study Type: observational
• Target: 100
• Locations: 2 countries
• Sites: 3

Brief Summary

Following heart transplantation (HTx), lifelong immunosuppressive treatment is required to prevent the immune system from attacking, damaging, and rejecting the donor hear (allograft). Currently, diagnosis of allograft rejection is based on evaluation of endomyocardial biopsies (EMB), which remains the gold standard for rejection diagnostics. However, previous research have highlighted limitations of EMBs, including interrater variation, sampling error and risks of complications. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising post-transplant biomarker of allograft rejection. Nevertheless, evidence suggests that dd-cfDNA demonstrates greater diagnostic performance for antibody-mediated rejection (AMR) than for cellular rejection (TCR) and that the specificity exceeds its sensitivity in predicting rejection, highlighting limitations in its clinical application. The primary objective of this observational project are to investigate if measurement of dd-cfDNA can be utilized as a biomarker for acute rejection in the management of heart transplant recipients during the first year after transplantation in a Danish-Norwegian patient cohort. Secondary objectives include:

• to correlate dd-cfDNA levels with markers of allograft dysfunction and rejection, i.e., EMBs, ejection fraction, left ventricular global longitudinal strain, troponin T, natriuretic peptide test (proBNP) and score of cardiac allograft vasculopathy (CAV)
• to examine post-transplant dd-cfDNA kinetics during the first 6 six weeks after HTx
• to explore clinical meaningful change in dd-cfDNA associated with acute allograft rejection
• to investigate the association between dd-cfDNA, chronic allograft rejection, allograft dysfunction and patients' long-term survival To study the objectives, this project will include 100 HTx patients prior to transplantation over a 2-3 year period and conduct a long-time follow up 10 years after transplantation. Patients entering the waiting list for HTx at Rigshospitalet Copenhagen, Denmark, Oslo University Hospital, Rikshospitalet Oslo, Norway, or Aarhus University Hospital, Denmark, are invited to participate in the project. Patients are invited to participate in the current project if fulfilling the pre-defined inclusion criteria and no exclusion criteria. A comprehensive collection of clinical, pathological and immunological data is conducted from up to 15 visits during the first year after transplantation. Thereafter, from all annual visits and upon admission if allograft rejection is suspected.

Conditions

Heart Transplantation

Keywords

Heart transplantation; Heart Failure; Donor-derived cell free DNA

Outcome Measures

Primary Outcomes (1)

• Association between dd-cfDNA level and acute allograft rejection (TCR and AMR) in the first year after transplantation, which will be evaluated using a linear mixed model and reported as the model estimate for the fixed effect (allograft rejection)

  From baseline to one year follow up

Secondary Outcomes (6)

• Association between dd-cfDNA level and acute allograft rejection in the 3rd, 5th and 10th year after transplantation implementing linear mixed models and reported as the model estimate for the fixed effect (allograft rejection)

  From baseline to 10 year follow up

• The area under the ROC curve (AUROC) depicting the performance of dd-cfDNA to distinguish between acute allograft rejection or no rejection in the 1st, 3rd, 5th and 10th year after transplantation.

  From baseline to 10 ten year follow up

• The sensitivity and positive predictive value (PPV) of dd-cfDNA as a biomarker of allograft rejection, i.e., the proportion of positive results (increased dd-cfDNA) that are true positive (developed rejection) after 1, 3, 5 and 10 years

  Baseline to 10 year follow up

• The specificity and negative predictive value (NPV) of dd-cfDNA as a biomarker of acute allograft rejection, i.e., the proportion of negative results (decreased/no change in dd-cfDNA) that are true negative (no rejection) after 1, 3, 5 and 10 years

  Baseline to 10 year follow up

• Change in the fraction of dd-cfDNA (dd-cfDNA kinetics) in patients without allograft rejection in the first six weeks after transplantation

  Baseline to 6 weeks afters transplantation

Other Outcomes (6)

• AUROC depicting the performance of current available biomarkers, including TnT to distinguish between acute allograft rejection or no rejection, and compare with AUROC statistics of dd-cfDNA

  Baseline to 1, 3, 5, and 10 year follow up

• Allograft dysfunction, i.e., frequency of patients developing moderate to severe CAV (CAV score ≥2) after year 1, 2, 5 and 10 of transplantation stratified by the number and type of rejection

  Baseline to 1, 3, 5, and 10 year follow up

• Correlation between dd-cfDNA levels, CAV progression and overall mortality during the 10-year project period

  Baseline to 10 year follow up

Study Arms (1)

Heart transplant recipients

Diagnostic Test: Donor-derived cell free DNA

Interventions

Donor-derived cell free DNA DIAGNOSTIC_TEST

Blood samples from months 1, 3, 6 and 12, and upon suspected allograft rejection, will be analysed to quantify dd-cfDNA studying the primary objective. To study additional objectives dd-cfDNA is further analyzed yearly after year 1 in all included patients. In a subgroup of patients without allograft rejection, dd-cfDNA will be analyed weekly within the first 6 weeks after transplantation to study normal dd-cfDNA kinetics after transplantation.

Heart transplant recipients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing heart transplantation at Rigshospitalet Copenhagen, Denmark, Rikshospitalet Oslo, Norway, or Aarhus University Hospital, Denmark

You may qualify if:

• Patients entering the waiting list for their first heart transplantation (HTX1) at Rigshospitalet Copenhagen, Denmark, Rikshospitalet Oslo, Norway, or Aarhus University Hospital, Denmark
• Patients ≥18 years old
• Patients signing informed consent

You may not qualify if:

• Patients who are withdrawn from the heart transplant waiting list after informed consent has been provided
• Patients who have previously received a solid organ transplantation
• Patients unable to receive and understand the oral and written project information

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Copenhagen University Hospital, Rigshospitalet: collaborator
• Oslo University Hospital: collaborator

Study Sites (3)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet Copenhagen

Copenhagen, 2100, Denmark

Location

Oslo University Hospital

Oslo, Norway

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, including EDTA-treated blood, Li-heparin-treated blood, serum and Streck plasma

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2026
• First Posted: October 21, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2038
• Last Updated: October 21, 2026

Record last verified: 2026-10

Locations

NO (1); DK (2)