PIONEER Trial (Post-Transplant Application of TruGraf and TRAC Molecular Panel in Renal Transplant Recipients)

Официальное название

Post-Transplant Application of TruGraf and TRAC Molecular Panel in Renal Transplant Recipients

Обзор

This is an observational, prospective, multi-center trial designed to evaluate clinical outcomes in kidney transplant recipients undergoing TruGraf and TRAC monitoring. Approximately 15 U.S. sites

Подробное описание

All subjects who meet the inclusion criteria and none of the exclusion criteria will be eligible to participate. As the study is non-interventional, no protocol-mandated treatment or management plan will be imposed. In the absence of a universally ac-cepted paradigm for post-transplant monitoring with molecular diagnostics, participat-ing sites will be encouraged to follow their usual practice, supplemented where ap-propriate by the suggested TruGraf and TRAC™ algorithms.

To evaluate both the prognostic performance and the clinical utility of these bi-omarkers, a hybrid analytic framework will be used. Biomarker results will be made available to clinicians in real time, and investigators will prospectively record whether each result led to a change in clinical management. Natural History Subgroup: Test-ing events in which both TruGraf® and TRAC results are double-negative and no change in management occurred. Analyses will be anchored at the test-event level to avoid immortal time bias. This subgroup will be used to evaluate the safety and true negative predictive value (NPV) of a double-negative result, including the incidence of biopsy-proven acute rejection (BPAR) within 30 days.

• Real-World Use Subgroup: Testing events in which biomarker results prompt-ed a change in clinical management (e.g., change in immunosuppression, for-cause biopsy, or enhanced monitoring). By definition, any action following a test result places the event in this subgroup, irrespective of whether the bi-omarker result was double-negative or abnormal. Because clinical actions can alter subsequent risk trajectories, analyses in this subgroup will account for treatment-confounder feedback using causal modeling strategies (e.g., marginal structural models, target trial emulation).

Вмешательства

• Диагностический тест There is no required Intervention for this Protocol. Based on Results for TruGraf/TRAC/TRAC ID Investigators may use the results in managing subjects Immunosuppression or rule out rejection.
  Investigators will prospectively record whether each results led to a change in clinical management. Participating sites will be encouraged to follow their usual practice, supplemented where appropriate by the suggested TruGraf and TRAC™ TRAC ID algorithms

Первичные конечные точки

• To evaluate post-transplant clinical outcomes in recipients of kidney transplants who are undergoing TruGraf and TRAC™ monitoring [Срок оценки: 24 Months post transplant]

Вторичные конечные точки (3)

• To evaluate the overall safety of TruGraf and TRAC monitoring in post-transplant recipients of kidney transplants. [Срок оценки: Month 3 to Mo 24 post transplant]
• To asses the safety of a double negative TruGraf/TRAC result [Срок оценки: Month 3 to Mo 24 post transplant]
• To explore the impact of biomarker -informed clinical decision-making on outcomes such as BPAR, estimated glomerular filtration rate (eGFR) trajectory, and immunosuppressive adjustments [Срок оценки: Month 3 to Mo 24 post transplant]

Критерии участия

Критерии включения

• Able to understand the key components of the study as described in the written informed consent document and willing and able to provide written informed consent.
• At least 18 years of age at the time of screening.
• Enrollment begins 30 days prior to transplant till day 29 post-transplantation.
• Recipient of a kidney transplant (either primary or repeat), from either deceased or living donor.
• Receiving any immunosuppressive regimen.
• Able and willing to comply with all study procedures, as assessed by the Investigator.
• Selected by the treating provider to undergo TruGraf and TRAC™ testing as part of routine post-transplant care

Критерии исключения

History of previous non-kidney solid organ, vascular composite allograft, pancreatic islet, stem cell, or bone marrow transplant.

• History of dual or en-bloc kidney transplants.
• Recipient or donor with positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV) nucleic acid testing (NAT), hepatitis C virus (HCV) antibody, HCV NAT, human immunodeficiency virus (HIV), or HIV NAT.
• Patients known to be pregnant or with plans to become pregnant over the 24 months after enrollment.
• History or presence of coagulopathy, thrombophilia, unexplained bleeding or clotting disorders, or use of or documented plans for use of systemic anticoagulants at the time of screening, with the exception of uremic coagulopathy or prophylactic heparin preparations.
• History or presence, upon clinical evaluation, of any illness or condition that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Clinical Utility of Peripheral Blood Gene Expression Profiling of Kidney Transplant Recipients to Assess the Need for Surveillance Biopsies in Subjects with Stable Renal Function January 2017 Journal of Transplantation Technologies & Research 07(03) DOI: 10.4172/2161-0991.1000177 Martin Roy First Thomas C Whisenant John Friedewald Show all 10 authors Michael M Abecassis Citations 6 Reads 239
• Analytical and Clinical Validation of a Molecular Diagnostic Signature in Kidney Transplant Recipients January 2017 Journal of Transplantation Technologies & Research 07(03) DOI: 10.4172/2161-0991.1000176
• Lo DJ, Kaplan B, Kirk AD. Biomarkers for kidney transplant rejection. Nat Rev Nephrol. 2014 Apr;10(4):215-25. doi: 10.1038/nrneph.2013.281. Epub 2014 Jan 21. PMID 24445740
• Bouamar R, Shuker N, Hesselink DA, Weimar W, Ekberg H, Kaplan B, Bernasconi C, van Gelder T. Tacrolimus predose concentrations do not predict the risk of acute rejection after renal transplantation: a pooled analysis from three randomized-controlled clinical trials(dagger). Am J Transplant. 2013 May;13(5):1253-61. doi: 10.1111/ajt.12191. Epub 2013 Mar 8. PMID 23480233
• Loupy A, Vernerey D, Tinel C, Aubert O, Duong van Huyen JP, Rabant M, Verine J, Nochy D, Empana JP, Martinez F, Glotz D, Jouven X, Legendre C, Lefaucheur C. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. J Am Soc Nephrol. 2015 Jul;26(7):1721-31. doi: 10.1681/ASN.2014040399. Epub 2015 Jan 2. PMID 25556173
• Heilman RL, Devarapalli Y, Chakkera HA, Mekeel KL, Moss AA, Mulligan DC, Mazur MJ, Hamawi K, Williams JW, Reddy KS. Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients. Am J Transplant. 2010 Mar;10(3):563-70. doi: 10.1111/j.1600-6143.2009.02966.x. Epub 2010 Feb 1. PMID 20121731
• Mehta RB, Tandukar S, Jorgensen D, Randhawa P, Sood P, Puttarajappa C, Zeevi A, Tevar AD, Hariharan S. Early subclinical tubulitis and interstitial inflammation in kidney transplantation have adverse clinical implications. Kidney Int. 2020 Aug;98(2):436-447. doi: 10.1016/j.kint.2020.03.028. Epub 2020 Apr 25. PMID 32624181
• Mehta R, Bhusal S, Randhawa P, Sood P, Cherukuri A, Wu C, Puttarajappa C, Hoffman W, Shah N, Mangiola M, Zeevi A, Tevar AD, Hariharan S. Short-term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol. Am J Transplant. 2018 Jul;18(7):1710-1717. doi: 10.1111/ajt.14627. Epub 2018 Jan 17. PMID 29247472

Идентификаторы

NCT: NCT07231328 · TGRP20_PIONEER

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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