Trifecta-Heart cfDNA-MMDx Study

NCT04707872 | Recruiting

• 1 other identifier: ATAGC06
• Study Type: observational
• Target: 300
• Locations: 7 countries
• Sites: 12

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.

Conditions

Heart Transplant Rejection

Keywords

Donor derived cfDNA; gene expression; heart transplant biopsy

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  18 month

• Report calibrated Prospera test results for rejection

  Obtain clinicians feedback

  6 months

• Report calibrated Prospera test results for heart injury

  Obtain clinicians feedback

  6 month

Secondary Outcomes (3)

• Determine if Prospera blood test can replace heart biopsy test

  6 month

• Determine if Prospera blood test can replace follow up heart biopsy

  6 month

• Assessment of donor-specific antibody status

  6 months

Study Arms (1)

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; Diagnostic Test: Prospera; Diagnostic Test: HLA antibody

Interventions

MMDx diagnostic test DIAGNOSTIC_TEST

Microarray test of gene expression in heart biopsies

Heart transplant protocol and for cause biopsies

Prospera DIAGNOSTIC_TEST

Donor derived cell-free DNA in patient blood

Heart transplant protocol and for cause biopsies

HLA antibody DIAGNOSTIC_TEST

Centralized measurement of HLA antibodies in patient blood

Heart transplant protocol and for cause biopsies

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• Patients will be excluded from the study if they decline participation
• Are unable to give informed consent.
• Recipients of multiple organs.

Sponsors & Collaborators

• University of Alberta: lead
• Natera, Inc.: collaborator
• One Lambda: collaborator

Study Sites (12)

Baptist Health Institute for Research and Innovation

Little Rock, Arkansas, 72205, United States

RECRUITING

Tampa General Hospital, 409 Bayshore Blvd.

Tampa, Florida, 33606, United States

RECRUITING

Columbia University Medical Center, Columbia Interventional Cardiovascular Care

West New York, New Jersey, 10032, United States

RECRUITING

Montefiore Medical Center, 3319 Rochambeau Avenue, 2nd FL

The Bronx, New York, 10467, United States

RECRUITING

Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute

Dallas, Texas, 75246, United States

RECRUITING

Cardiovascular Medicine, University of Utah Health

Salt Lake City, Utah, 84132, United States

RECRUITING

Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute

Darlinghurst, NSW 2010, Australia

NOT YET RECRUITING

Division of Cardiology, University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

RECRUITING

Institute for Clinical and Experimental Medicine - IKEM Videnska 1958/9

Prague, 140 21, Czechia

RECRUITING

Heart Failure and Heart Transplant Unit, University of Bologna

Bologna, 40138, Italy

NOT YET RECRUITING

Silesian Center for Heart Diseases (Ś!ąskie Centrum Chorób Serca w Zabrzu

Zabrze, 41-800, Poland

RECRUITING

Advanced Heart Failure Transplant Unit

A Coruña, Spain

NOT YET RECRUITING

Related Publications (6)

• Madill-Thomsen KS, Halloran PF. Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope(R) Diagnostic System (MMDx). Clin Sci (Lond). 2024 Jun 5;138(11):663-685. doi: 10.1042/CS20220530.

  PMID: 38819301 BACKGROUND

• Halloran PF, Madill-Thomsen KS. Donor-derived Cell-free DNA: A Step Forward in the Quest for Transplant Truth. Transplantation. 2025 Jun 1;109(6):910-914. doi: 10.1097/TP.0000000000005332. Epub 2025 Jan 28. No abstract available.

  PMID: 39883025 BACKGROUND

• Halloran PF, Reeve J, Mackova M, Madill-Thomsen KS, Demko Z, Olymbios M, Campbell P, Melenovsky V, Gong T, Hall S, Stehlik J. Comparing Plasma Donor-derived Cell-free DNA to Gene Expression in Endomyocardial Biopsies in the Trifecta-Heart Study. Transplantation. 2024 Sep 1;108(9):1931-1942. doi: 10.1097/TP.0000000000004986. Epub 2024 Aug 20.

  PMID: 38538559 RESULT

• Madill-Thomsen KS, Hidalgo LG, Mackova M, Campbell P, Demko Z, Felius J, Gong T, Hall S, Kim DH, Kuczaj A, Lowe D, Maliakkal N, Melenovsky V, Olympios M, Patel S, Prewett A, Przybylowski P, Sayer G, Stehlik J, Tseliou E, Uriel N, Halloran PF. Defining the relationships among four tests for assessing antibody-mediated rejection in heart transplants in a prospective, observational study. J Heart Lung Transplant. 2025 Nov 13:S1053-2498(25)02363-0. doi: 10.1016/j.healun.2025.10.024. Online ahead of print.

  PMID: 41241034 RESULT

• Madill-Thomsen KS, Hidalgo LG, Mackova M, Demko Z, Prewett A, Campbell P, Felius J, Gong T, Hall S, Kim D, Kuczaj A, Lowe D, Maliakkal N, Melenovsky V, Olympios M, Patel S, Przybylowski P, Sayer G, Tseliou E, Uriel N, Stehlik J, Halloran PF; Trifecta-Heart Study Group. Comparing DSA-negative and DSA-positive antibody-mediated rejection in heart transplants: results from the Trifecta-Heart study. J Heart Lung Transplant. 2026 Mar 13:S1053-2498(26)01771-7. doi: 10.1016/j.healun.2026.03.004. Online ahead of print.

  PMID: 41833593 RESULT

• Halloran PF, Madill-Thomsen KS. The Molecular Microscope Diagnostic System: Assessment of Rejection and Injury in Heart Transplant Biopsies. Transplantation. 2023 Jan 1;107(1):27-44. doi: 10.1097/TP.0000000000004323. Epub 2022 Dec 8.

  PMID: 36508644 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

RNA isolated from patient biopsy.

Study Officials

• Philip F Halloran, MD PhD

  Alberta Transplant Applied Genomics Center, University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Konrad Famulski, PhD

CONTACT

1 780 782 9463; konrad@ualberta.ca

Robert Polakowski, PhD

CONTACT

1 780 492 5091; polakows@ualberta.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 13, 2021
• Study Start: June 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); PL (1); ES (1); CZ (1); US (6); CA (1); IT (1)