Biomarkers / Blood, Biopsy, Immunosuppression Management, Kidney Transplant Rejection, Subclinical Rejection
Conditions
Keywords
TRAC-ID ASSAY, Kidney Transplant rejection, TruGraf, TRAC/TRAC ID biomarker panel, TruGraf, TRAC
Brief summary
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
Detailed description
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).
Interventions
DIAGNOSTIC_TESTThere 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
Sponsors
Medical University of South Carolina
Northwestern University
The Cleveland Clinic
University of Washington
University of California, Los Angeles
University of Nebraska
Duke University
University of Utah
Georgetown University
Virginia Commonwealth University
The Methodist Hospital Research Institute
Keck School of Medicine USC
Weill Medical College of Cornell University
Erie County Medical Center
East Carolina University
AdventHealth
Transplant Genomics, Inc.
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
* 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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate post-transplant clinical outcomes in recipients of kidney transplants who are undergoing TruGraf and TRAC™ monitoring | 24 Months post transplant | The primary endpoint is a composite at 24-months post-transplant, defined as the occurrence of any of the following events: • Biopsy-proven acute rejection (BPAR) on any for-cause biopsy between Month 1 to Month 24 (local read). OR • De novo Class I or Class II DSA detected at Month 12 or Month 24 (centrally read). OR • Decline in eGFR ≥20% from Month 3 to Month 24, calculated using the CKD-EPI creatinine-based equation. OR • Three or more abnormal TruGraf and TRAC results between Months 1 and 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the overall safety of TruGraf and TRAC monitoring in post-transplant recipients of kidney transplants. | Month 3 to Mo 24 post transplant | Actions taken based on tests results TruGraf, TRAC/TRAC-ID |
| To asses the safety of a double negative TruGraf/TRAC result | Month 3 to Mo 24 post transplant | Quantifying the incidence of biopsy -proven acute rejection (BPAR) withing 30 days among patients for whom no change in clinical management was undertaken |
| To explore the impact of biomarker -informed clinical decision-making on outcomes such as BPAR, estimated glomerular filtration rate (eGFR) trajectory, and immunosuppressive adjustments | Month 3 to Mo 24 post transplant | Quantifying the incidence of biopsy -proven acute rejection (BPAR) withing 30 days among patients for whom no change in clinical management was undertaken |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory objective: Evaluate the utility of serial TRAC-ID assays to monitor viral or systemic infections and guide safe adjustments of immunosuppression | Mont 3- Mo 24 | TRAC-ID results will be available for Investigators |
Contacts
Primary ContactIsioma Agboli, Assistant Director, Clinical Programs, MD
Backup ContactIulia Movileanu, Senior Clinical Trial Manager, MS CCRP
Outcome results
None listed