Trifecta-Heart cfDNA-MMDx-studie
Trifecta-Heart cfDNA-MMDX-studie: Sammenligning av DD-cfDNA-testen med MMDx Microarray Test og 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.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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
Studietype
Registrering (Antatt)
Kontakter og plasseringer
Studiekontakt
- Navn: Robert Polakowski, PhD
- Telefonnummer: 1 780 492 5091
- E-post: polakows@ualberta.ca
Studer Kontakt Backup
- Navn: Konrad Famulski, PhD
- Telefonnummer: 1 780 782 9463
- E-post: konrad@ualberta.ca
Studiesteder
-
-
-
Darlinghurst, Australia, NSW 2010
- Har ikke rekruttert ennå
- Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute
-
Hovedetterforsker:
- Peter MacDonald, MD
-
Ta kontakt med:
- Carmen Herrera, MD
- E-post: peter.macdonal@svha.org.au
-
-
-
-
Alberta
-
Edmonton, Alberta, Canada, T6G 2R7
- Rekruttering
- Division of Cardiology, University of Alberta
-
Hovedetterforsker:
- Daniel Kim, MD
-
Ta kontakt med:
- Daniel Kim, MD
- E-post: dk@ualberta.ca
-
-
-
-
Arkansas
-
Little Rock, Arkansas, Forente stater, 72205
- Rekruttering
- Baptist Health Institute for Research and Innovation
-
Hovedetterforsker:
- Patrick Campbell, MD
-
Ta kontakt med:
- Victoria McIntosh Marren
- E-post: victoria.mcintosh@baptist-health.org
-
-
Florida
-
Tampa, Florida, Forente stater, 33606
- Rekruttering
- Tampa General Hospital, 409 Bayshore Blvd.
-
Ta kontakt med:
- Kristyn Kuzianik
- E-post: kkuzianik@tgh.org
-
Hovedetterforsker:
- Benjamin Mackie, MD
-
-
New Jersey
-
West New York, New Jersey, Forente stater, 10032
- Rekruttering
- Columbia University Medical Center, Columbia Interventional Cardiovascular Care
-
Hovedetterforsker:
- Gabriel Sayer, MD
-
Ta kontakt med:
- Maria Alejandra Muñoz Cifuentes
- E-post: mam2649@cumc.columbia.edu
-
-
New York
-
The Bronx, New York, Forente stater, 10467
- Rekruttering
- Montefiore Medical Center, 3319 Rochambeau Avenue, 2nd FL
-
Ta kontakt med:
- Renae Robinson
- E-post: rerobins@montefiore.org
-
Ta kontakt med:
- Brandon Johnson
- E-post: brajohnson@montefiore.org
-
Hovedetterforsker:
- Omar Saeed, MD
-
-
Texas
-
Dallas, Texas, Forente stater, 75246
- Rekruttering
- Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute
-
Ta kontakt med:
- Aayla K Jamil, MBBS
- E-post: Aayla.Jamil@BSWHealth.org
-
Hovedetterforsker:
- Shelley Hall, MD
-
-
Utah
-
Salt Lake City, Utah, Forente stater, 84132
- Rekruttering
- Cardiovascular Medicine, University of Utah Health
-
Ta kontakt med:
- Jennifer Hong
- E-post: Jennifer.Hong@hsc.utah.edu
-
Hovedetterforsker:
- Josef Stehlik, MD, PhD
-
-
-
-
-
Bologna, Italia, 40138
- Har ikke rekruttert ennå
- Heart Failure and Heart Transplant Unit, University of Bologna
-
Hovedetterforsker:
- Luciano Potena, MD
-
Ta kontakt med:
- Laura Borgese
- E-post: laura.borgese@gmail.com
-
-
-
-
-
Zabrze, Polen, 41-800
- Rekruttering
- Silesian Center for Heart Diseases (Ś!ąskie Centrum Chorób Serca w Zabrzu
-
Hovedetterforsker:
- Piotr Przybylowski, Professor
-
Ta kontakt med:
- Agnieszka Kuczaj, MD PhD
- E-post: agnieszka.kuczaj@gmail.com
-
-
-
-
-
A Coruña, Spania
- Har ikke rekruttert ennå
- Advanced Heart Failure Transplant Unit
-
Hovedetterforsker:
- Maria G Crespo-Leiro, MD
-
Ta kontakt med:
- Zulaika Grille Cancela
- E-post: Zulaika.grille.cancela@sergas.es
-
-
-
-
-
Prague, Tsjekkia, 140 21
- Rekruttering
- Institute for Clinical and Experimental Medicine - IKEM Videnska 1958/9
-
Ta kontakt med:
- Tereza Novakowa
- E-post: novt@ikem.cz
-
Hovedetterforsker:
- Vojtech Melenovsky, MD PhD
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
- Eldre voksen
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Prøvetakingsmetode
Studiepopulasjon
The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications or surveillance (protocol) biopsy.
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Observasjonsmodeller: COHORT
- Tidsperspektiver: PROSPECTIVE
Kohorter og intervensjoner
Gruppe / Kohort |
Intervensjon / Behandling |
|---|---|
|
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. |
Microarray test of gene expression in heart biopsies Donor derived cell-free DNA in patient blood Centralized measurement of HLA antibodies in patient blood |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Calibration of Prospera test for T cell-mediated rejection
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 6 months
|
Obtain clinicians feedback |
6 months
|
|
Report calibrated Prospera test results for heart injury
Tidsramme: 6 month
|
Obtain clinicians feedback |
6 month
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Determine if Prospera blood test can replace heart biopsy test
Tidsramme: 6 month
|
Obtain clinicians feedback |
6 month
|
|
Determine if Prospera blood test can replace follow up heart biopsy
Tidsramme: 6 month
|
Determine whether resolution of DD-cfDNA after treatment can monitor response to therapy and avoid follow-up biopsies |
6 month
|
|
Assessment of donor-specific antibody status
Tidsramme: 6 months
|
Report and compare the DSA status based on centralized and local HLA antibody measurement. |
6 months
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Philip F Halloran, MD PhD, Alberta Transplant Applied Genomics Center, University of Alberta
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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. 2026 Apr;45(4):659-670. doi: 10.1016/j.healun.2025.10.024. Epub 2025 Nov 13.
- Madill-Thomsen KS, Hidalgo LG, Mackova M, Demko Z, Prewett A, Campbell P, Felius J, Gong T, Hall S, Kim DH, 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 Jul;45(7):1046-1057. doi: 10.1016/j.healun.2026.03.004. Epub 2026 Mar 13.
- Halloran PF, Madill-Thomsen KS, Biagini DG, Kaur N, Prewett A, Suresh N, Demko ZP, Bhorade S, Olympios M, Gauthier PT, Campbell PT, Gong T, Hall S, Kim DH, Kuczaj A, Przybylowski P, Melenovsky V, Patel SR, Sayer G, Stehlik J, Tseliou E, Uriel N, Mackova M; Trifecta-Heart Investigators. A two-threshold donor-derived cell-free DNA algorithm improves detection of molecular rejection in heart transplantation. J Heart Lung Transplant. 2026 Jun 22:S1053-2498(26)01953-4. doi: 10.1016/j.healun.2026.06.009. Online ahead of print.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- ATAGC06
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
Only IPD data will be shared within a participating center.
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .