A National Swedish Study Evaluating Dd-cfDNA for as a Diagnostic Biomarker for Rejection Surveillence in Heart Transplantation

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorKarolinska Institutet

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 volunteers

Qualifiers

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

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • dd-cfDNA

    Diagnostic test

    Analysis of correlation between analyzed dd-cfDNA fraction levels and biopsy-proven rejection,

Treatment groups

120 Participants
are divided into 1 treatment group
Group A: Heart transplant patients1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
through study completion, an average of 1 year

Secondary outcomes

Other outcomes

1

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.

Time frame
From enrolment up to five years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Karolinska Institutet

Lead sponsor

Region Stockholm

Collaborator