An observational study in Heart Transplant Rejection, sponsored by University of Alberta. Recruiting at 12 sites in 7 countries. Per ClinicalTrials.gov, last updated 2026-10-06.
Sponsored by University of Alberta · Observational
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.
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 718 biopsies, 709 cfDNA samples and 706 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
University of Alberta is the lead sponsor of 800 studies on the registry; 168 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications or surveillance (protocol) biopsy.
Exclusion Criteria:
The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications as standard of care, or protocol biopsies of heart in high-risk patients, or follow-up after treatment.
Diagnostic Test: MMDx diagnostic test · Diagnostic Test: Prospera · Diagnostic Test: HLA antibody
Microarray test of gene expression in heart biopsies
Donor derived cell-free DNA in patient blood
Centralized measurement of HLA antibodies in patient blood
Calibration of Prospera test for T cell-mediated rejection
Set DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx. Calibration of DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.
Time frame: 18 months
Calibration of Prospera test for antibody-mediated rejection
Set DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.
Time frame: 18 months
Calibration of Prospera test for heart injury
Set DD-cfDNA test cut-off values against the probability of acute and chronic heart injury in the biopsy as reported by MMDx.
Time frame: 18 month
Report calibrated Prospera test results for rejection
Obtain clinicians feedback
Time frame: 6 months
Report calibrated Prospera test results for heart injury
Obtain clinicians feedback
Time frame: 6 month
Determine if Prospera blood test can replace heart biopsy test
Obtain clinicians feedback
Time frame: 6 month
Determine if Prospera blood test can replace follow up heart biopsy
Determine whether resolution of DD-cfDNA after treatment can monitor response to therapy and avoid follow-up biopsies
Time frame: 6 month
Assessment of donor-specific antibody status
Report and compare the DSA status based on centralized and local HLA antibody measurement.
Time frame: 6 months
Plan to share: No — Only IPD data will be shared within a participating center.
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 ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Alberta