About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adults (≥18 years) who undergo orthotopic HTx.
Disqualifiers
Pregnancy,
Multi-organ transplantation
Solid organ
Hematopoietic stem cell transplantation.
Trial population
This study will include adult HTx recipients from Skåne University Hospital (Lund), Sahlgrenska University Hospital (Gothenburg), and Karolinska University Hospital (Stockholm). 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.
Trial design
Cohort
Prospective
Treatments tested in this trial
dd-cfDNA
Diagnostic testAnalysis of correlation between analyzed dd-cfDNA fraction levels and biopsy-proven rejection,
Treatment groups
Trial outcomes
Primary outcomes
Correlation between dd-cfDNA fraction levels and biopsy-proven rejection
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.
Other outcomes
Incidence of graft dysfunction and cardiac allograft vasculopathy (CAV) + association between ddcf-DNA and biomarkers
A. The primary outcome is the correlation between dd-cfDNA levels and biopsy-proven rejection (per ISHLT criteria). Longitudinal changes in dd-cfDNA and DSA, will be analyzed. B. Incidence of graft dysfunction and CAV during 5 year follow up will be studied and the association between DSA, dd-cfDNA and outcome will be analyzed. C. Association between dd-cfDNA and circulating biomarkers of graft injury or inflammation will be anlayzed. 1\. Rejection is defined as pAMR1(H+) pAMR1(I+) pAMR2 pAMR3 ACR grade 2R ACR 3R Non-rejection: pAMR0 2. dd-cfDNA is measured as * Fractional Abundance (%): ≥0.2% specific for biopsy-proven acute rejection 3. DSA is measured as Mean Fluorescence Intensity (MFI). * An MFI threshold \>5000 is used to define positivity. 4. Graft dysfunction is measured as LVEF \<40%. 5. CAV is measured as * CAV 0 (none) * CAV 1 (mild) * CAV 2 (moderate) * CAV 3 (severe) 4. B. It is not known today which biomarkers of graft injury or inflammation will be analyzed.
Sponsors and contacts
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Karolinska Institutet
Lead sponsor
Region Stockholm
Collaborator