ID-ENTITY Trial- Evaluating Serial T-ID Monitoring

Official title

A Prospective, Multicenter, Observational Study Evaluating Serial T-ID Monitoring for the Prevention of CMV Disease and BK Virus-Associated Nephropathy Following Kidney Transplantation

Overview

To evaluate the association between time-updated CMV and BK viral loads measured monthly by T-ID and the risk of CMV disease and/or biopsy-proven BK virus-associated nephropathy (BKVAN) during the first 12 months following kidney transplantation, accounting for the net immune environment (TTV viral load) and allograft injury (donor-derived cell-free DNA, dd-cfDNA).

Detailed description

* To characterize time-updated viral detection patterns (e.g., transient vs sustained CMV or BK signals) identified by T-ID prior to development of CMV disease or BKVAN. * To evaluate the clinical utility of T-ID monitoring, defined by the frequency and type of clinical management actions taken following test results. * To estimate the diagnostic performance of T-ID for clinically meaningful viral infection compared with standard-of-care (PCR) testing and clinical adjudication. * To quantify lead time between T-ID detection of viral cfDNA and standard-of-care confirmation or initiation of therapy. * To assess the safety of biomarker-informed management, including both rejection following infection-directed management and infection following rejection-directed management.

Interventions

• Diagnostic test Blood tests, TRAC( cell free DNA) and T-ID
  Blood collection

Primary outcome measures

• The primary endpoint of the study is the time to first occurrence of either cytomegalovirus (CMV) disease or biopsy-proven BK virus-associated nephropathy (BKVAN) during the first 12 months post-kidney transplantation. [Time frame: 12 Months]

Eligibility criteria

Inclusion criteria

• Participants must meet all the following criteria:

• Written informed consent and HIPAA authorization obtained prior to any study-related data collection.
• Age ≥18 years at the time of enrollment.
• Recipient of a kidney transplant, including:
• Primary or repeat kidney transplantation
• Living-donor or deceased-donor transplantation
• At 1 month post-kidney transplant at the time of enrollment.
• Receiving maintenance immunosuppressive therapy per institutional standard of care.
• Selected by the treating provider to undergo TRAC testing as part of usual post-transplant clinical monitoring.

Exclusion criteria

• Recipient of a combined organ transplant involving a non-renal solid organ (e.g., kidney-liver, kidney-heart) and/or islet cell transplantation.
• History of prior non-renal solid organ transplantation or islet cell transplantation.
• Known pregnancy at the time of enrollment.
• Known active viral infection at enrollment with any of the following:
• Hepatitis B surface antigen (HBsAg)-positive
• Hepatitis B virus (HBV) nucleic acid testing (NAT)-positive
• Human immunodeficiency virus (HIV) infection or HIV NAT-positive
• \*Known active BK virus-associated nephropathy (BKVAN) or CMV disease at the time of enrollment.
• Medical, psychiatric, or social condition that, in the opinion of the Investigator, would interfere with the participant's ability to provide informed consent or comply with study procedures.
• Concurrent participation in another investigational biomarker study designed to evaluate clinical utility of post-transplant molecular diagnostics.

• Participants with asymptomatic or low-level viral replication detected during routine clinical monitoring are eligible, provided there is no evidence of established CMV disease or BK virus-associated nephropathy at enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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
• Arms MA, Fleming J, Sangani DB, Nadig SN, McGillicuddy JW, Taber DJ. Incidence and impact of adverse drug events contributing to hospital readmissions in kidney transplant recipients. Surgery. 2018 Feb;163(2):430-435. doi: 10.1016/j.surg.2017.09.027. Epub 2017 Nov 22. PMID 29174434
• Sinha R, Zhu Z, Park S, Rebello C, Kinsella B, Friedewald J, Kleiboeker S. Combined Metagenomic Viral Detection and Donor-Derived Cell-Free DNA Quantification in Plasma From Kidney Transplant Recipients. Transplant Proc. 2024 Jul-Aug;56(6):1522-1530. doi: 10.1016/j.transproceed.2024.06.003. Epub 2024 Jul 6. PMID 38972761
• Park S, Guo K, Heilman RL, Poggio ED, Taber DJ, Marsh CL, Kurian SM, Kleiboeker S, Weems J, Holman J, Zhao L, Sinha R, Brietigam S, Rebello C, Abecassis MM, Friedewald JJ. Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2021 Oct;16(10):1539-1551. doi: 10.2215/CJN.05530421. PMID 34620649
• Friedewald JJ, Kurian SM, Heilman RL, Whisenant TC, Poggio ED, Marsh C, Baliga P, Odim J, Brown MM, Ikle DN, Armstrong BD, Charette JI, Brietigam SS, Sustento-Reodica N, Zhao L, Kandpal M, Salomon DR, Abecassis MM; Clinical Trials in Organ Transplantation 08 (CTOT-08). Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney tran PMID 29985559
• 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, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen JP, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B PMID 32463180

Identifiers

NCT: NCT07393594 · TGRP32 ID-ENTITY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗