CLinical Utility of the omnigrAf® biomarkeR Panel In The Care of kidneY Transplant Recipients

Study Overview
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Brief Summary
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This is a prospective, multi-site, observational study with a matched control group. The primary objective is to evaluate change in renal function over time in recipients of kidney transplants who are undergoing OmniGrafTM monitoring in conjunction with patient medication-related burden monitoring.

Detailed Description
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The survival benefits of solid organ transplants in the United States are well documented. Improvements in immunosuppression, better anti-microbial agents, and other aspects of ancillary care have resulted in significant improvements in short- term outcomes; however, there has been little improvement in long-term graft loss. A more recent analysis found that 65% of hospital readmissions in kidney transplant recipients had adverse drug events (ADE) considered contributory, and ADE-associated readmissions had a significantly higher hazard or graft loss and death compared to patients with readmissions not associated with an ADE. Even with knowledge of ADEs, clinicians may be reluctant to adjust immunosuppressive medications due to concerns of rejection risk during the period of medication adjustment. The OmniGrafTM biomarker panel (Transplant Genomics, Inc, Framingham, MA) includes the TruGraf® peripheral blood expression profile and the TRAC donor-derived cell-free DNA(dd-cfDNA) test, which have demonstrated a strong ability to identify immune quiescence in stable patients post kidney transplant, with a NPV of 94% when both tests are negative and a PPV of 89% for subclinical rejection when both tests are positive. Because of the strong rule out capabilities of OmniGrafTM, it would be an ideal complement to real-time ADE knowledge to help guide clinicians' decisions to adjust, or not adjust, the immunosuppressive regimen, and help provide a dialogue between patients and clinicians on the risk-benefit of medication adjustments. The aim of this study is to evaluate change in renal function over time in recipients of kidney transplants who are undergoing OmniGrafTM monitoring in conjunction with patient medication-related burden monitoring.

Official Title
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CLinical Utility of the omnigrAf® biomarkeR Panel In The Care of kidneY Transplant Recipients

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Patients monitored with OmniGraf testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent and HIPAA authorization; At least 18 years of age; Recipient of a primary or subsequent deceased-donor or living-donor kidney transplant; Between 3 months and 2 years post-transplant; Selected by provider to undergo OmniGraf™ testing as part of usual post-transplant care Exclusion Criteria: Recipient of a combined organ transplant with an extra-renal organ and/or islet cell transplant; Recipient of a previous non-renal solid organ and/or islet cell transplant; Known to be pregnant; Known to be infected with Human Immunodeficiency Virus (HIV); Known to have active BK nephropathy; Known to have nephrotic proteinuria (per principal investigator); or Participation in other biomarker studies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients monitored with OmniGraf Testing<br>Subjects will have OmniGraf™ testing at study enrollment and thereafter every 3 months or at the same time as standard routine labs (minimum two per year). In addition, subjects will have OmniGraf™ testing at any time there is a workup for clinical events and referral to advanced care (transplant center, biopsy, etc) | Diagnostic Test: Patients monitored with OmniGraf testing<br>* This is an observational study there are no protocol mandated interventions. OmniGraf results will be utilized in conjunction with standard of care assessments to determine patient management.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GFR changes between study group and matched control group | Comparison of the slope change in estimated glomerular filtration rate (eGFR), calculated using the MDRD 4-variable equation and CKD-EPI, from baseline to the end of follow-up between study participants and a matched control group. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMISE and Self efficacy results from baseline to study completion | Comparison of the Patient-Reported Outcomes Measurement Information System(PROMIS) Self-Efficacy for Managing Chronic Conditions - Managing Medications and Treatment-Short Form 4a (Self-Efficacy) at the end of follow-up to baseline PROMIS tools were developed to be disease non-specific measures of health-related domains. Each domain in composed of an item bank specific to a trait being measured. Item banks are calibrated on a common scale to facilitate comparability across varying populations. Depression is measured by various questions with answers ranging from never to always. Raw scores are transformed to standardized T-score metrics, with a mean of 50 and standard deviation of 10 | 3 years | 
| PROMISE results from baseline to study completion | Comparison of the PROMIS-29 Profile v2.1 at the end of follow-up to baseline PROMIS tools were developed to be disease non-specific measures of health-related domains. Each domain in composed of an item bank specific to a trait being measured. Item banks are calibrated on a common scale to facilitate comparability across varying populations. Depression is measured by various questions with answers ranging from never to always. Raw scores are transformed to standardized T-score metrics, with a mean of 50 and standard deviation of 10 | 3 years | 
| PROMIS Depression scale from baseline to study completion | Comparison of the PROMIS Depression scale at the end of follow-up to baseline. PROMIS tools were developed to be disease non-specific measures of health-related domains such as self-efficacy for symptom and medication management, depression, anxiety, fatigue, pain interference, sleep disturbance, and physical functioning. Each domain in composed of an item bank specific to a trait being measured. Item banks are calibrated on a common scale to facilitate comparability across varying populations. Depression is measured by various questions with answers ranging from never to always. | 3 years | 
| Comparison of Hospitlizations due to infections in the matched control and study group | Rate of hospitalizations, subcategorized for hospitalizations due to infections, compared between study participants and a matched control group | 3 years | 
| Comparison of rejection of matched control and study group | Incidence of treated rejections, compared between study participants and a matched control group | 3 years | 
| MRSB | Medication-Related Symptom Burden (MRSB), as defined as the change in number and severity of adverse effects | 3 years | 
| Graft survival at 3 years comparison of matched control vs. study group | Proportion of subjects with overall graft survival (including death with a functioning allograft) at year 3 post-transplant, compared between study participants and a matched control group | 3 years | 
| Graft survival at 1-2 years comparison of matched control vs. study group | Proportion of subjects with overall graft survival at year 1 and year 2 post-enrollment, compared between study participants and a matched control group | 2 years | 
| Graft loss during study period | Number of participants with graft loss, defined as permanent return to dialysis, retransplantation or patient death at any time during the 3-year primary follow-up study period; | 3 years | 
| Graft survival during study period | Graft survival calculated from the date of kidney transplantation until date of graft loss | 3 years | 
| Death-censored graft loss | Number of participants with death-censored graft loss, defined as permanent return to dialysis or retransplantation at any time during the 3-year primary follow-up study period. Patients who die with a functioning graft will be right censored | 3 years | 
| Patient death during study period | Number of participants with patient death from any cause at any time during the 3-year primary follow-up study period | 3 years | 
| Provider changes during study period | Rate of change in provider satisfaction from baseline to the end of follow-up using questionnaire | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Subclinical Rejection, Immunosuppression