Evaluation of the Added Clinical Value of Donor-derived Cell-free DNA for the Monitoring of Cardiac Allograft Rejection.

NCT06740578 | Completed

• 1 other identifier: HEART-FREE
• Study Type: observational
• Target: 320
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this observational study is to assess the clinical added value of donor-derived cell-free DNA (dd-cfDNA) to monitor cardiac allograft rejection. The main question it aims to answer is whether dd-cfDNA is independently associated with rejection and if it allows a significant improvement in individual risk stratification of rejection on top of a robust predictive model based on standard clinical and biological predictive variables.

Conditions

Heart Transplantation; Rejection Heart Transplant

Keywords

heart transplantation; donor-derived cell-free DNA; non-invasive biomarker; allograft rejection; risk stratification

Outcome Measures

Primary Outcomes (1)

• Number of patients with biopsy proven rejection and / or acute allograft dysfunction

  * acute cellular rejection ≥ 2R according to the international society for heart and lung transplantation working formulation * antibody-mediated rejection ≥ pAMR1 according to the international society for heart and lung transplantation working formulation * acute allograft dysfunction defined as an unknown left ventricular ejection fraction - LVEF \< 0.50 and/or acute drop in LVEF ≥ 0.15 compared to baseline evaluation.

  12 months

Secondary Outcomes (2)

• Independent association between donor-derived cell-free DNA and allograft ejection

  12 months

• Individual risk stratification

  12 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Prospective cohort of heart transplant recipients (\> 30 days post-transplant)

You may qualify if:

• heart transplant recipients,
• heart transplantation performed for more than 30 days,
• clinical indication of an endomyocardial biopsy, either protocol or for cause,
• informed consent

You may not qualify if:

• multiorgan transplantation
• refusal to participate

Sponsors & Collaborators

• Paris Translational Research Center for Organ Transplantation: lead

Study Sites (2)

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

Georges Pompidou European Hospital

Paris, 75015, France

Location

Related Publications (7)

• Kobashigawa J, Hall S, Shah P, Fine B, Halloran P, Jackson AM, Khush KK, Margulies KB, Sani MM, Patel JK, Patel N, Peyster E; conference participants. The evolving use of biomarkers in heart transplantation: Consensus of an expert panel. Am J Transplant. 2023 Jun;23(6):727-735. doi: 10.1016/j.ajt.2023.02.025. Epub 2023 Mar 3.

  PMID: 36870390 RESULT

• Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, Andersen CB, Angelini A, Berry GJ, Burke MM, Demetris AJ, Hammond E, Itescu S, Marboe CC, McManus B, Reed EF, Reinsmoen NL, Rodriguez ER, Rose AG, Rose M, Suciu-Focia N, Zeevi A, Billingham ME. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005 Nov;24(11):1710-20. doi: 10.1016/j.healun.2005.03.019. Epub 2005 Jun 20.

  PMID: 16297770 RESULT

• Teszak T, Bodor C, Hegyi L, Levay L, Nagy B, Fintha A, Merkely B, Sax B. Local laboratory-run donor-derived cell-free DNA assay for rejection surveillance in heart transplantation-first six months of clinical experience. Clin Transplant. 2023 Sep;37(9):e15078. doi: 10.1111/ctr.15078. Epub 2023 Jul 25.

  PMID: 37489087 RESULT

• Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant. 2011 Jun;30(6):601-11. doi: 10.1016/j.healun.2011.02.015. No abstract available.

  PMID: 21555100 RESULT

• Coutance G, Kransdorf E, Aubert O, Bonnet G, Yoo D, Rouvier P, Duong Van Huyen JP, Bruneval P, Taupin JL, Leprince P, Varnous S, Kobashigawa J, Jouven X, Patel J, Loupy A. Clinical Prediction Model for Antibody-Mediated Rejection: A Strategy to Minimize Surveillance Endomyocardial Biopsies After Heart Transplantation. Circ Heart Fail. 2022 Oct;15(10):e009923. doi: 10.1161/CIRCHEARTFAILURE.122.009923. Epub 2022 Oct 6.

  PMID: 36200456 RESULT

• Agbor-Enoh S, Shah P, Tunc I, Hsu S, Russell S, Feller E, Shah K, Rodrigo ME, Najjar SS, Kong H, Pirooznia M, Fideli U, Bikineyeva A, Marishta A, Bhatti K, Yang Y, Mutebi C, Yu K, Kyoo Jang M, Marboe C, Berry GJ, Valantine HA; GRAfT Investigators. Cell-Free DNA to Detect Heart Allograft Acute Rejection. Circulation. 2021 Mar 23;143(12):1184-1197. doi: 10.1161/CIRCULATIONAHA.120.049098. Epub 2021 Jan 13.

  PMID: 33435695 RESULT

• Velleca A, Shullo MA, Dhital K, Azeka E, Colvin M, DePasquale E, Farrero M, Garcia-Guereta L, Jamero G, Khush K, Lavee J, Pouch S, Patel J, Michaud CJ, Shullo MA, Schubert S, Angelini A, Carlos L, Mirabet S, Patel J, Pham M, Urschel S, Kim KH, Miyamoto S, Chih S, Daly K, Grossi P, Jennings DL, Kim IC, Lim HS, Miller T, Potena L, Velleca A, Eisen H, Bellumkonda L, Danziger-Isakov L, Dobbels F, Harkess M, Kim D, Lyster H, Peled Y, Reinhardt Z. The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2023 May;42(5):e1-e141. doi: 10.1016/j.healun.2022.10.015. Epub 2022 Dec 20. No abstract available.

  PMID: 37080658 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples collected at the time of an endomyocardial biopsy

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: December 18, 2024
• Study Start: October 1, 2021
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: January 3, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)