Kidney Transplant Rejection
Conditions
Brief summary
This is an observational study to evaluate safety and efficacy outcomes in renal transplant recipients in whom post-transplant care is managed using AlloSure®. AlloSure® is a non-invasive test to measure donor-derived cell-free DNA (dd-cfDNA). The AlloSure test is intended to assess the probability of allograft rejection in kidney transplant recipients with clinical suspicion of rejection and to inform clinical decision-making regarding the necessity of renal biopsy in such patients at least 2 weeks post-transplant in conjunction with standard clinical assessment. Amendment 1 (A1): Is an observational study to develop and validate the clinical use of KidneyCare®.
Detailed description
The AlloSure test has been approved for Medicare coverage for clinical use when a physician determines there is a need to assess the probability of allograft rejection in kidney transplant recipients. The DART study suggests that use of the non-invasive AlloSure test to measure donor-derived cell-free DNA (dd-cfDNA) can be used to discriminate active rejection in a renal transplant recipient. Use of the test may reduce invasive percutaneous renal biopsy procedures among patients with a suspicion of rejection. Amendment 1 (A1) is intended to enable the development of KidneyCare® which is a panel test which includes the clinically validated commercial AlloSure dd-cfDNA test, combined with AlloMap Kidney which is a peripheral blood gene expression profiling test currently under development, and iBox, which is an analytic platform that predicts allograft survival at 3, 5, 7 and 10 years using a proprietary software algorithm based on a number of clinical inputs. The AlloMap Kidney and the iBox components are not yet clinically validated and so will not be used for patient management and are being developed through this study.
Interventions
DIAGNOSTIC_TESTDonor-derived cell-free DNA (AlloSure®)
Patients will receive donor-derived cell-free DNA testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.
OTHERStandard care
Current standard methods for monitoring of renal allograft recipients for rejection (e.g. donor-specific antibodies, serum creatinine, proteinuria, renal allograft biopsy)
DIAGNOSTIC_TESTPeripheral blood gene expression profiling (AlloMap Kidney)
Patients will receive peripheral blood gene expression profiling testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.
DIAGNOSTIC_TESTAnalytic platform (IBox)
Patients will receive IBox testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.
Sponsors
CareDx
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
KOAR Inclusion Criteria: 1. Patient's health care provider adopts and intends to apply the center's AlloSure Routine Testing Schedule as part of the information used to manage the patient. 2. Subjects willing to provide written informed consent to participate. KOAR
Exclusion criteria
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Exclusions for AlloSure® Intended Use Specimens from patients for whom any of the following are true will not be tested: 1. Recipients of transplanted organs other than kidney 2. Recipients of a transplant from a monozygotic (identical) 3. Recipients of a bone marrow transplant 4. Recipients who are pregnant 5. Recipients who are under the age of 18 6. Recipient who are less than 14 days post-transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Interstitial fibrosis/tubular atrophy (IF/TA) quantified by Banff Working Group biopsy grade(s) at 12 months post-transplant in AlloSure® and renal allograft biopsy managed patients | Feb-2020 |
| Total number of biopsies planned and performed post-transplant, including both surveillance and clinically indicated biopsies | Feb-2020 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Predictive Value (NPV) of AlloSure for active rejection | Dec-2022 | — |
| Positive Predictive Value (PPV) of AlloSure for active rejection | Dec-2022 | — |
| Develop and validate the clinical use of KidneyCare® | Dec-2022 | — |
| Sensitivity of AlloSure for active rejection | Dec-2022 | — |
| Transplant glomerulopathy (TG) | Dec-2022 | Evaluated at one-year post-transplant, quantified by biopsy-based histopathology grade(s) |
| Patient and graft survival | Dec-2022 | Evaluated at years 1, 2, and 3 post-transplant |
| Serum creatinine | Dec-2022 | Evaluated at years 1, 2, and 3 post-transplant |
| Estimated glomerular filtration rate | Dec-2022 | Evaluated at years 1, 2, and 3 post-transplant |
| Specificity of AlloSure for active rejection | Dec-2022 | — |
Countries
United States
Outcome results
None listed