Trifecta-Heart cfDNA-MMDx Study

Status Recruiting

Clinical Trial 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.

Clinical Trial 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 258 biopsies and 216 corresponding cfDNA samples. Due to a considerable interest from participation centers, this study aims to collect 400 biopsies and corresponding blood samples. This study is an extension of the INTERHEART ClinicalTrials.gov Identifier: NCT02670408 ;

Study Design

Related Conditions & MeSH terms

Heart Transplant Rejection

Clinical Trial Details

NCT number	NCT04707872
Study type	Observational
Source	University of Alberta
Contact	Konrad Famulski, PhD
Phone	1 780 782 9463
Email	konrad@ualberta.ca
Status	Recruiting
Phase
Start date	June 1, 2021
Completion date	July 2025

View Details

See also
Status	Clinical Trial	Phase
Active, not recruiting	`NCT05205551` - Prospera Test Evaluation in Cardiac Transplant (ProTECT)
Completed	`NCT06436027` - Molecular Diagnosis of Heart Allograft Rejection Using Intra-Graft Targeted Gene Expression Profiling.
Not yet recruiting	`NCT05732779` - Mobile Video Directly Observed Therapy (DOT) for Immunosuppression Medication Adherence in Adolescent Heart Transplant Recipients	N/A
Active, not recruiting	`NCT05064462` - TTV Viral Load in Heart Transplant Recipients
Recruiting	`NCT04973943` - Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection
Completed	`NCT03477383` - A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
Not yet recruiting	`NCT05772442` - Cardiac Transplant Metabolomics With and Without Rejection
Recruiting	`NCT06064123` - Biomarkers for Diagnosis, Prognosis, and Targeted Therapy After Heart Transplantation
Active, not recruiting	`NCT04921774` - Research on Patients With Heart Transplantation
Recruiting	`NCT04226521` - Extracorporeal Photopheresis and Early Cardiac Graft Vasculopathy	N/A
Completed	`NCT03393793` - HEart trAnsplantation Registry of piTie-Salpetriere University Hospital
Completed	`NCT01136135` - Cardiac Magnetic Resonance Imaging (CMRI) for Detection of Cardiac Transplant Rejection	N/A
Completed	`NCT03833050` - The TOGETHER Project - Heart
Active, not recruiting	`NCT03373227` - Phase II Study Evaluating the Efficacy of Tacrolimus Extended Release Tablets to Twice Daily Tacrolimus Dosing Regimen	Phase 2
Active, not recruiting	`NCT03695601` - Surveillance HeartCare® Outcomes Registry
Active, not recruiting	`NCT01397812` - Heartsbreath Test for Heart Transplant Rejection	N/A
Active, not recruiting	`NCT05184426` - MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.