An observational study in Heart Transplantation, sponsored by University of Aarhus. Enrolling by invitation at 3 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by University of Aarhus · Observational
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 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.
5,803 studies on the registry are indexed under Heart Failure; 1,222 are open to participants now.
This study's planned enrollment of 100 is below the median of 200 across 1,719 observational studies indexed under Heart Failure.
Browse Heart Failure studies →University of Aarhus is the lead sponsor of 1,299 studies on the registry; 189 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients undergoing heart transplantation at Rigshospitalet Copenhagen, Denmark, Rikshospitalet Oslo, Norway, or Aarhus University Hospital, Denmark
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Diagnostic Test: Donor-derived cell free DNA
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.
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)
Time frame: From baseline to one year follow up
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)
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline to 6 weeks afters transplantation
Correlation between dd-cfDNA level, clinical findings (GLS, biopsy results, etc.) and patient characteristics
Time frame: Baseline to 1, 3, 5, and 10 year follow up
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
Time frame: 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
Time frame: 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
Time frame: Baseline to 10 year follow up
The frequency of patients developing HLA antibodies over the 10-year project and the correlation to overall mortality stratified by type of donor-specific HLA antibodies and strengths
Time frame: Baseline to 1, 3, 5, and 10 year follow up
Correlation between HLA antibodies (type and strength), dd-cfDNA level and overall mortality
Time frame: Baseline to 1, 3, 5, and 10 year follow up
Patient survival 10 years after heart transplantation
Time frame: Baseline to 5 and 10 year follow up
Plan to share: Undecided — Due to restrictions imposed by Danish and Norwegian data protection legislation, individual participant-level data cannot be made publicly available or shared with third party. Project data may be made available upon reasonable request and subject to appropriate collaboration agreements, in accordance with applicable Danish and Norwegian data protection legislation.
No publications or documents are linked to this record.
Started Sep 2026 (actual). Primary completion is estimated for Aug 2029, 35 months after the start.
Of 665 non-industry observational studies under Heart Failure, half reached primary completion within 44 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 89. This study's planned 35 months is below that.
Counting every sponsor, half of 825 studies reached it within 40 months; a quarter within 21 and three quarters within 80.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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