Official Title
Trifecta-Heart cfDNA-MMDX Study: Comparing the DD-cfDNA Test to MMDx Microarray Test and Central HLA Antibody Test
Brief Title
Trifecta-Heart cfDNA-MMDx Study
Protocol ID
NCT04707872
Lead Sponsor
University of Alberta
Brief Summary
Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood
transplant recipient and the Molecular Microscope® (MMDx) Diagnostic System results in
indication and protocol biopsies from heart transplants.
Detailed Description
The current standard for assessment of rejection in heart transplants is an
endomyocardial biopsy (EMB) interpreted by histology according to ISHLT guidelines. This
has considerable error rates, many due to the high disagreement among pathologists in
assessing lesions and diagnoses. To address the unmet need for precision and accuracy,
the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has
developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx),
which uses microarrays to define the global gene expression features of rejection and
injury. Now a new screening test is being introduced: the monitoring of donor-derived
cell-free DNA (DD-cfDNA) released in the blood by the heart during rejection. The Natera
Inc DD-cfDNA Prospera® test is based on the massively multiplex polymerase chain reaction
that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified
by Next Generation Sequencing. The Prospera® test has been done on kidney transplant
recipients and detected "active rejection" and differentiated it from borderline
rejection and no rejection. However, Prospera® test was not examined (the DD-cfDNA
results) in heart transplant recipients. DD-cf-DNA test for heart transplants must now be
calibrated against MMDx that is based on global gene expression, the new standard for
biopsy interpretation. The present study will calibrate centrally measured (Natera Inc)
DD-cfDNA levels obtained at the time of an indication or protocol biopsy against the MMDx
measurements of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR) and
early and late tissue injury. The present study will compare DD-cfDNA and MMDx in 300
prospectively collected biopsies for clinical indications and protocol, and accompanying
600 blood samples, to calibrate the DD-cfDNA (Natera Inc.) levels against the MMDx biopsy
diagnoses of TCMR, ABMR (and its stages), and acute (early) and chronic (late) injury, ,
as well as central assessment of HLA antibody (One Lambda) in 300 blood samples,
interpreted centrally as donor specific antibody (DSA) based on the tissue typing
results. Trifecta-Heart collected 680 biopsies, 669 cfDNA samples and 656 One Lambda
samples so far. Due to a considerable interest from participation centers, this study
aims to collect 300 more biopsies and corresponding blood samples. This study is an
extension of the INTERHEART ClinicalTrials.gov Identifier: NCT02670408
Study Period
Enrollment Count
300 participants
Eligibility Criteria
Inclusion Criteria:
- All heart transplant recipients undergoing a biopsy for clinical indications and
protocol biopsies, as determined by their physician or surgeon, will be eligible to
enroll in the study.
- Patients are enrolled based on standard of care biopsies, including surveillance
biopsies in high-risk patients, with informed consent.
Exclusion Criteria:
- Patients will be excluded from the study if they decline participation
- Are unable to give informed consent.
- Recipients of multiple organs.
Filters
Heart Transplant Rejection
RECRUITING
CHILD
ADULT
OLDER_ADULT