Trifecta-심장 cfDNA-MMDx 연구
Trifecta-심장 cfDNA-MMDX 연구: DD-cfDNA 테스트와 MMDx 마이크로어레이 테스트 및 중앙 HLA 항체 테스트 비교
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.
연구 개요
상세 설명
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
연구 유형
등록 (추정된)
연락처 및 위치
연구 연락처
- 이름: Robert Polakowski, PhD
- 전화번호: 1 780 492 5091
- 이메일: polakows@ualberta.ca
연구 연락처 백업
- 이름: Konrad Famulski, PhD
- 전화번호: 1 780 782 9463
- 이메일: konrad@ualberta.ca
연구 장소
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Arkansas
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Little Rock, Arkansas, 미국, 72205
- 모병
- Baptist Health Institute for Research and Innovation
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수석 연구원:
- Patrick Campbell, MD
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연락하다:
- Victoria McIntosh Marren
- 이메일: victoria.mcintosh@baptist-health.org
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Florida
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Tampa, Florida, 미국, 33606
- 모병
- Tampa General Hospital, 409 Bayshore Blvd.
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연락하다:
- Kristyn Kuzianik
- 이메일: kkuzianik@tgh.org
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수석 연구원:
- Benjamin Mackie, MD
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New Jersey
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West New York, New Jersey, 미국, 10032
- 모병
- Columbia University Medical Center, Columbia Interventional Cardiovascular Care
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수석 연구원:
- Gabriel Sayer, MD
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연락하다:
- Maria Alejandra Muñoz Cifuentes
- 이메일: mam2649@cumc.columbia.edu
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New York
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The Bronx, New York, 미국, 10467
- 모병
- Montefiore Medical Center, 3319 Rochambeau Avenue, 2nd FL
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연락하다:
- Renae Robinson
- 이메일: rerobins@montefiore.org
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연락하다:
- Brandon Johnson
- 이메일: brajohnson@montefiore.org
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수석 연구원:
- Omar Saeed, MD
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Texas
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Dallas, Texas, 미국, 75246
- 모병
- Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute
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연락하다:
- Aayla K Jamil, MBBS
- 이메일: Aayla.Jamil@BSWHealth.org
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수석 연구원:
- Shelley Hall, MD
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Utah
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Salt Lake City, Utah, 미국, 84132
- 모병
- Cardiovascular Medicine, University of Utah Health
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연락하다:
- Jennifer Hong
- 이메일: Jennifer.Hong@hsc.utah.edu
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수석 연구원:
- Josef Stehlik, MD, PhD
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A Coruña, 스페인
- 아직 모집하지 않음
- Advanced Heart Failure Transplant Unit
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수석 연구원:
- Maria G Crespo-Leiro, MD
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연락하다:
- Zulaika Grille Cancela
- 이메일: Zulaika.grille.cancela@sergas.es
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Bologna, 이탈리아, 40138
- 아직 모집하지 않음
- Heart Failure and Heart Transplant Unit, University of Bologna
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수석 연구원:
- Luciano Potena, MD
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연락하다:
- Laura Borgese
- 이메일: laura.borgese@gmail.com
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Prague, 체코, 140 21
- 모병
- Institute for Clinical and Experimental Medicine - IKEM Videnska 1958/9
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연락하다:
- Tereza Novakowa
- 이메일: novt@ikem.cz
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수석 연구원:
- Vojtech Melenovsky, MD PhD
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Alberta
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Edmonton, Alberta, 캐나다, T6G 2R7
- 모병
- Division of Cardiology, University of Alberta
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수석 연구원:
- Daniel Kim, MD
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연락하다:
- Daniel Kim, MD
- 이메일: dk@ualberta.ca
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Zabrze, 폴란드, 41-800
- 모병
- Silesian Center for Heart Diseases (Ś!ąskie Centrum Chorób Serca w Zabrzu
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수석 연구원:
- Piotr Przybylowski, Professor
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연락하다:
- Agnieszka Kuczaj, MD PhD
- 이메일: agnieszka.kuczaj@gmail.com
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Darlinghurst, 호주, NSW 2010
- 아직 모집하지 않음
- Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute
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수석 연구원:
- Peter MacDonald, MD
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연락하다:
- Carmen Herrera, MD
- 이메일: peter.macdonal@svha.org.au
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참여기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
샘플링 방법
연구 인구
The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications or surveillance (protocol) biopsy.
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 관찰 모델: COHORT
- 시간 관점: PROSPECTIVE
코호트 및 개입
그룹/코호트 |
개입 / 치료 |
|---|---|
|
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 |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Calibration of Prospera test for T cell-mediated rejection
기간: 18 months
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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
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Calibration of Prospera test for antibody-mediated rejection
기간: 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
|
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Calibration of Prospera test for heart injury
기간: 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
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Report calibrated Prospera test results for rejection
기간: 6 months
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Obtain clinicians feedback |
6 months
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Report calibrated Prospera test results for heart injury
기간: 6 month
|
Obtain clinicians feedback |
6 month
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Determine if Prospera blood test can replace heart biopsy test
기간: 6 month
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Obtain clinicians feedback |
6 month
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Determine if Prospera blood test can replace follow up heart biopsy
기간: 6 month
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Determine whether resolution of DD-cfDNA after treatment can monitor response to therapy and avoid follow-up biopsies |
6 month
|
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Assessment of donor-specific antibody status
기간: 6 months
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Report and compare the DSA status based on centralized and local HLA antibody measurement. |
6 months
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Philip F Halloran, MD PhD, Alberta Transplant Applied Genomics Center, University of Alberta
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- ATAGC06
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
Only IPD data will be shared within a participating center.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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