TRU-IMMUNO: Optimizing Liver Immunosuppression

Study Overview
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Brief Summary
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This is a prospective, multi-center, randomized study. The primary objective is to evaluate the feasibility and utility of TruGraf/TRAC Liver testing used in addition to standard of care measures of liver dysfunction to guide immunosuppression management.

Detailed Description
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This study will provide TruGraf Liver and TRAC liver tests to one group of transplant providers early after liver transplantation to clarify if the Trugraf Liver and TRAC Liver results can complement their immunosuppression minimization strategies to avoid complications and reduce the occurrence of acute rejection. The ability to decrease IS will be compared to the group that does not receive the test results. Subjects will be randomized into 2 groups: one will receive Trugraf/TRAC Liver testing and the other will not. Subjects in the biomarker arm will have TruGraf Liver and TRAC Liver testing at study enrollment (1-2 months post-liver transplant) and thereafter every month for 6 months. Subjects will also have Trugraf Liver and TRAC Liver testing at months 9 and 12 following transplantation (7-8 and 10-11 months post baseline). The TruGraf and TRAC Liver results will be used in the biomarker arm in conjunction with all other clinical parameters available to guide decisions related to immunosuppression changes. There are no protocol mandated immunosuppression changes. Subjects in the standard of care arm will not have biomarkers available for decisions related to immunosuppression changes.

Official Title
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A Clinical Pilot Study to Test the Acceptability and Feasibility of TruGraf Liver and TRAC Liver Testing as Part of Standard of Care: Optimizing Liver ImmunoSuppression (TRU-IMMUNO)

Conditions
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Liver Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Patients monitored with TruGraf and TRAC Liver testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age. Recipient of a primary or subsequent deceased-donor or living donor liver transplantation. Normal liver function tests at the time of or within 2 weeks of the baseline visit, defined by Total Bilirubin (TB) ≤1.5 mg/dL and Direct Bilirubin (DB) <0.5 mg/dL, Alkaline Phosphatase (AP) ≤200 U/L, and Alanine Transaminase (ALT) ≤60 U/L (males) ≤36 U/L (females). Between 1-2 months post-liver transplantation Exclusion Criteria: Inability or unwillingness to provide informed consent. Recipients of previous hepatic or non-hepatic solid organ transplantation History of ≥2 mild or moderate rejections or 1 severe rejection prior to enrollment defined by BANFF 2016 criteria History of autoimmune liver disease Listed for repeat liver transplantation Infection with HIV Active HBV or HCV viremia (patients with undetectable virus can be included)

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 TruGraf/TRAC Liver testing<br>Subjects in the biomarker arm will have TruGraf Liver and TRAC Liver testing at study enrollment (1-2 months post-liver transplant) and thereafter every month for 6 months. Subjects will also have Trugraf Liver and TRAC Liver testing at months 9 and 12 following transplantation (7-8 and 10-11 months postbaseline) The TruGraf and TRAC Liver results will be used in the biomarker arm in conjunction with all other clinical parameters available to guide decisions of the Principal Investigator and Sub-Investigators related to immunosuppression management. changes. | Diagnostic Test: Patients monitored with TruGraf and TRAC Liver testing<br>* This is an observational study there are no protocol mandated interventions. TruGraf and TRAC Liver results will be utilized in conjunction with standard of care assessments to determine patient management in the study arm.<br>|
| Patients not monitored with TruGraf/TRAC Liver testing<br>Patients in control/ stamdard of care arm will have immusuppresion reduction based on the clinical judgement and management of the Principal Investigator and Sub-Investigators. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunosuppression reduction | Percent of subjects in each arm achieving at least 50% reduction from baseline total immunosuppressant (non-corticosteroid) dose at 6 months | 6-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunosuppressant trough | Immunosuppressant trough levels at 6 months post transplant | 6-months | 
| Median and mean IS trough | Median and mean change in IS trough levels from baseline to 6 months | 6-months | 
| monotherapy immunosuppression | Percent of patients achieving monotherapy immunosuppression | 1 year | 
| clinical utility | Percent and total number of TruGraf Liver and TRAC Liver results that the PI identified as having clinical utility (Utility). | 1 year | 
| Liver testing workflow | Percent and total number of eligible patients for whom the PI was able to complete the entire TruGraf Liver and TRAC Liver testing workflow (Feasibility). | 1 year | 
| CKD score | Progression of CKD score managed by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria from a scale of GI (normal kidney) to G5 (kidney failure) | 1 year | 
| BPAR for-cause biopsy | Incidence of biopsy proven acute rejection on a for cause biopsy at months 6 and 12 | 1 year | 
| Acute rejection | Incidence of clinically treated acute rejection at months 6 and 12 | 1 year | 
| eGFR timepoints | eGFR at months 6 and 12 | 1 year | 
| eGFR timepoint range | eGFR change from baseline to months 6 and 12 | 1 year | 
| Slope of eGFR | Slope of eGFR from baseline to months 6 and 12 | 1 year | 
| eGFR decline or progression of CKD | Risk factors for eGFR decline or progression of CKD score | 1 year | 
| Infections | Incidence of grade 3 or greater infections at months 6 and 12 | 1 year | 
| SF-36 scores | Change in SF-36 scores from baseline to 6 months and end of study (SF 36 is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. | 1 year | 

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