A National Swedish Study Evaluating Donor-derived Cell-free DNA as a Diagnostic Biomarker in Heart Transplantation (SweD-HTx)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Karolinska Institutet
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Correlation between dd-cfDNA fraction levels and biopsy-proven rejection
Study Overview
Brief Summary
The SweD-HTx-study is an observational, multicenter cohort study including adult HTx recipients from Skåne University Hospital (Lund), Sahlgrenska University Hospital (Gothenburg), and Karolinska University Hospital (Stockholm). The aim of the study is to establish a robust, nationwide protocol for dd-cfDNA-based rejection monitoring in Swedish HTx recipients and to enhance our understanding of rejection mechanisms and immune activation. All participants undergo endomyocardial biopsies as part of routine post-transplant surveillance. Heart transplantations are performed at Skåne University Hospital or Sahlgrenska University Hospital, with post-transplant follow-up conducted at the outpatient transplant clinics at the participating centers.
Eligible participants are adults (≥18 years) who undergo orthotopic HTx. Exclusion criteria include pregnancy, multi-organ transplantation, or a history of other solid organ or hematopoietic stem cell transplantation.
Peripheral blood samples are collected according to standardized operating procedures and transported at ambient temperature to the immunology laboratory for processing. A subset of samples is immediately cryopreserved upon collection. Clinical and demographic data are extracted from the electronic medical record (EMR) using standardized data collection forms. The main outcome is the correlation between analyzed dd-cfDNA fraction levels and biopsy-proven rejection, defined by International Society of Heart and Lung Transplantation (ISHLT)'s histopathological criteria. The longitudinal changes in dd-cfDNA fraction and DSA will be analyzed as well as the association between DSA and dd-cfDNA fraction.
Detailed Description
Introduction:
Heart transplantation (HTx) and left ventricular assist device (LVAD) therapy are the primary treatment options for advanced heart failure. While HTx improves survival, it presents both short- and long-term risks, including immune-mediated injury and adverse effects from immunosuppressants. Cardiac allograft rejection affects 15-20% of recipients and often necessitates increased immunosuppression. Early detection is crucial, and serial endomyocardial biopsies (EMBs) remain the standard surveillance method.
Recently, biomarkers such as donor-derived cell-free DNA (dd-cfDNA) have emerged for detecting inflammation and cellular damage. Dd-cfDNA reflects apoptosis and necrosis in the transplanted organ and can be measured as a fraction of total cell-free DNA via PCR-based assays. It is a sensitive marker of early antibody-mediated rejection (AMR) and acute cellular rejection (ACR), often rising before histopathological changes are seen. In the US, dd-cfDNA assays are common post-transplant, but in Europe, their use is limited by cost and access.
In Sweden, 60-70 heart transplants are performed each year, with national protocols guiding post-transplant care. Frequent EMBs are performed in the first year. There is a need for non-invasive monitoring to reduce patient discomfort and improve diagnostics. This study aims to establish a national dd-cfDNA testing protocol using next-generation sequencing and to advance understanding of rejection and immune activation.
Materials and Methods:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults (≥18 years) who undergo orthotopic HTx.
Exclusion Criteria
- •Pregnancy,
- •Multi-organ transplantation
- •Solid organ
- •Hematopoietic stem cell transplantation.
Arms & Interventions
Heart transplant patients
Intervention: dd-cfDNA (Diagnostic Test)
Outcomes
Primary Outcomes
Correlation between dd-cfDNA fraction levels and biopsy-proven rejection
Time Frame: through study completion, an average of 1 year
The main outcome is the correlation between analyzed dd-cfDNA fraction levels and biopsy-proven rejection, defined by International Society of Heart and Lung Transplantation (ISHLT)'s histopathological criteria. The longitudinell changes in dd-cfDNA fraction and DSA will be analyzed as well as the the association between DSA and dd-cfDNA fraction.
Secondary Outcomes
No secondary outcomes reported
Investigators
Michael Melin, MD
Senior consultant
Karolinska Institutet