Trifecta-心脏 cfDNA-MMDx 研究
Trifecta-Heart cfDNA-MMDX 研究：比较 DD-cfDNA 测试与 MMDx 微阵列测试和中央 HLA 抗体测试
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.
研究概览
详细说明
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
研究类型
注册 (估计的)
联系人和位置
学习联系方式
- 姓名：Robert Polakowski, PhD
- 电话号码：1 780 492 5091
- 邮箱：polakows@ualberta.ca
研究联系人备份
- 姓名：Konrad Famulski, PhD
- 电话号码：1 780 782 9463
- 邮箱：konrad@ualberta.ca
学习地点
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Alberta
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Edmonton、Alberta、加拿大、T6G 2R7
- 招聘中
- Division of Cardiology, University of Alberta
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首席研究员：
- Daniel Kim, MD
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接触：
- Daniel Kim, MD
- 邮箱：dk@ualberta.ca
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Bologna、意大利、40138
- 尚未招聘
- Heart Failure and Heart Transplant Unit, University of Bologna
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首席研究员：
- Luciano Potena, MD
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接触：
- Laura Borgese
- 邮箱：laura.borgese@gmail.com
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Prague、捷克语、140 21
- 招聘中
- Institute for Clinical and Experimental Medicine - IKEM Videnska 1958/9
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接触：
- Tereza Novakowa
- 邮箱：novt@ikem.cz
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首席研究员：
- Vojtech Melenovsky, MD PhD
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Zabrze、波兰、41-800
- 招聘中
- Silesian Center for Heart Diseases (Ś!ąskie Centrum Chorób Serca w Zabrzu
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首席研究员：
- Piotr Przybylowski, Professor
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接触：
- Agnieszka Kuczaj, MD PhD
- 邮箱：agnieszka.kuczaj@gmail.com
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Darlinghurst、澳大利亚、NSW 2010
- 尚未招聘
- Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute
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首席研究员：
- Peter MacDonald, MD
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接触：
- Carmen Herrera, MD
- 邮箱：peter.macdonal@svha.org.au
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Arkansas
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Little Rock、Arkansas、美国、72205
- 招聘中
- Baptist Health Institute for Research and Innovation
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首席研究员：
- Patrick Campbell, MD
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接触：
- Victoria McIntosh Marren
- 邮箱：victoria.mcintosh@baptist-health.org
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Florida
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Tampa、Florida、美国、33606
- 招聘中
- Tampa General Hospital, 409 Bayshore Blvd.
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接触：
- Kristyn Kuzianik
- 邮箱：kkuzianik@tgh.org
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首席研究员：
- Benjamin Mackie, MD
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New Jersey
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West New York、New Jersey、美国、10032
- 招聘中
- Columbia University Medical Center, Columbia Interventional Cardiovascular Care
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首席研究员：
- Gabriel Sayer, MD
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接触：
- Maria Alejandra Muñoz Cifuentes
- 邮箱：mam2649@cumc.columbia.edu
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New York
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The Bronx、New York、美国、10467
- 招聘中
- Montefiore Medical Center, 3319 Rochambeau Avenue, 2nd FL
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接触：
- Renae Robinson
- 邮箱：rerobins@montefiore.org
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接触：
- Brandon Johnson
- 邮箱：brajohnson@montefiore.org
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首席研究员：
- Omar Saeed, MD
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Texas
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Dallas、Texas、美国、75246
- 招聘中
- Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute
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接触：
- Aayla K Jamil, MBBS
- 邮箱：Aayla.Jamil@BSWHealth.org
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首席研究员：
- Shelley Hall, MD
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Utah
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Salt Lake City、Utah、美国、84132
- 招聘中
- Cardiovascular Medicine, University of Utah Health
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接触：
- Jennifer Hong
- 邮箱：Jennifer.Hong@hsc.utah.edu
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首席研究员：
- Josef Stehlik, MD, PhD
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A Coruña、西班牙
- 尚未招聘
- Advanced Heart Failure Transplant Unit
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首席研究员：
- Maria G Crespo-Leiro, MD
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接触：
- Zulaika Grille Cancela
- 邮箱：Zulaika.grille.cancela@sergas.es
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参与标准
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
有资格学习的性别
取样方法
研究人群
The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications or surveillance (protocol) biopsy.
描述
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.
学习计划
研究是如何设计的？
设计细节
- 观测模型：COHORT
- 时间观点：PROSPECTIVE
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
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 |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Calibration of Prospera test for T cell-mediated rejection
大体时间：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
大体时间：18 months
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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
大体时间：18 month
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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
大体时间：6 months
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Obtain clinicians feedback |
6 months
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Report calibrated Prospera test results for heart injury
大体时间：6 month
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Obtain clinicians feedback |
6 month
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Determine if Prospera blood test can replace heart biopsy test
大体时间：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
大体时间：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
大体时间：6 months
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Report and compare the DSA status based on centralized and local HLA antibody measurement. |
6 months
|
合作者和调查者
调查人员
- 首席研究员：Philip F Halloran, MD PhD、Alberta Transplant Applied Genomics Center, University of Alberta
出版物和有用的链接
一般刊物
- 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.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他研究编号
- ATAGC06
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
Only IPD data will be shared within a participating center.
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