Trifecta-Heart cfDNA-MMDx Study

April 2, 2024 updated by: University of Alberta

Trifecta-Heart cfDNA-MMDX Study: Comparing the DD-cfDNA Test to MMDx Microarray Test and Central HLA Antibody Test

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 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 Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Darlinghurst, Australia, NSW 2010
        • Not yet recruiting
        • Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute
        • Principal Investigator:
          • Peter MacDonald, MD
        • Contact:
  • Austria
      • Vienna, Austria, A-1090
        • Not yet recruiting
        • Department of Cardiac Surgery, Medical University of Vienna
        • Principal Investigator:
          • Andreas Zuckerman, MD
        • Contact:
        • Sub-Investigator:
          • Johannes Gokler, MD
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2R7
        • Recruiting
        • Division of Cardiology, University of Alberta
        • Principal Investigator:
          • Daniel Kim, MD
        • Contact:
  • Czechia
      • Prague, Czechia, 140 21
        • Recruiting
        • Institute for Clinical and Experimental Medicine - IKEM Videnska 1958/9
        • Contact:
        • Principal Investigator:
          • Vojtech Melenovsky, MD PhD
  • Italy
      • Bologna, Italy, 40138
        • Not yet recruiting
        • Heart Failure and Heart Transplant Unit, University of Bologna
        • Principal Investigator:
          • Luciano Potena, MD
        • Contact:
  • Poland
      • Zabrze, Poland, 41-800
        • Recruiting
        • Silesian Center for Heart Diseases (Ś!ąskie Centrum Chorób Serca w Zabrzu
        • Contact:
        • Principal Investigator:
          • Piotr Przybylowski, Professor
  • Spain
      • La Coruna, Spain
        • Recruiting
        • Advanced Heart Failure Transplant Unit
        • Principal Investigator:
          • Maria G Crespo-Leiro, MD
        • Contact:
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • Baptist Health Institute for Research and Innovation
        • Principal Investigator:
          • Patrick Campbell, MD
        • Contact:
    • California
      • Los Angeles, California, United States, 90024
        • Not yet recruiting
        • UCLA Medical Centre
        • Contact:
        • Principal Investigator:
          • Martin Cadeiras, MD
        • Sub-Investigator:
          • Mario Deng, MD
      • Los Angeles, California, United States, 90048
    • New Jersey
      • W. New York, New Jersey, United States, 10032
        • Recruiting
        • Columbia University Medical Center, Columbia Interventional Cardiovascular Care
        • Principal Investigator:
          • Gabriel Sayer, MD
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute
        • Contact:
        • Principal Investigator:
          • Shelley Hall, MD
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • Cardiovascular Medicine, University of Utah Health
        • Contact:
        • Principal Investigator:
          • Josef Stehlik, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications or surveillance (protocol) biopsy.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Heart transplant protocol and for cause biopsies
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
Microarray test of gene expression in heart biopsies
Diagnostic test: Prospera
Donor derived cell-free DNA in patient blood
Diagnostic test: HLA antibody
Centralized measurement of HLA antibodies in patient blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Calibration of Prospera test for T cell-mediated rejection
Time Frame: 18 months
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.
18 months
Calibration of Prospera test for antibody-mediated rejection
Time Frame: 18 months
Set DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.
18 months
Calibration of Prospera test for heart injury
Time Frame: 18 month
Set DD-cfDNA test cut-off values against the probability of acute and chronic heart injury in the biopsy as reported by MMDx.
18 month
Report calibrated Prospera test results for rejection
Time Frame: 6 months
Obtain clinicians feedback
6 months
Report calibrated Prospera test results for heart injury
Time Frame: 6 month
Obtain clinicians feedback
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of donor-specific antibody status
Time Frame: 6 months
Report and compare the DSA status based on centralized and local HLA antibody measurement.
6 months
Determine if Prospera blood test can replace heart biopsy test
Time Frame: 6 month
Obtain clinicians feedback
6 month
Determine if Prospera blood test can replace follow up heart biopsy
Time Frame: 6 month
Determine whether resolution of DD-cfDNA after treatment can monitor response to therapy and avoid follow-up biopsies
6 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alberta

Collaborators

Natera, Inc.
One Lambda

Investigators

  • Principal Investigator: Philip F Halloran, MD PhD, Alberta Transplant Applied Genomics Center, University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2021

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

January 11, 2021

First Submitted That Met QC Criteria

January 11, 2021

First Posted (Actual)

January 13, 2021

Study Record Updates

Last Update Posted (Actual)

April 4, 2024

Last Update Submitted That Met QC Criteria

April 2, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATAGC06

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Only IPD data will be shared within a participating center.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Transplant Rejection

Clinical Trials on MMDx diagnostic test

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe