EVITA Study - Epstein-Barr Virus Infection moniToring in renAl Transplant Recipients

Study Overview
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Brief Summary
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Transplant recipients are treated with immunosuppressive drugs to avoid rejection of the transplanted organ. As the medication impairs the immune response, it also increases the risk of serious infections and cancer in transplant recipients compared with the general population. Previous studies have shown a close association between Epstein-Barr virus (EBV) and post transplant lymphoproliferative disorder (PTLD), with frequent demonstration of the virus in lesional tissues. Transplant recipients without evidence of EBV infection prior to transplantation (EBV seronegative) are at particularly high risk of developing PTLD. Other risk factors include a high viral load. As part of a preventive approach against PTLD, several transplantation units now monitor the occurrence of EBV DNAemia after transplantation. However, there is little evidence to guide this strategy; nor is there consensus concerning either the best specimen to use for EBV analysis (whole blood or plasma) or the appropriate clinical action to take if EBV DNAemia is detected. Our aim is to estimate the incidence and clinical consequences of Epstein-Barr virus (EBV) DNAemia in whole blood and plasma in renal transplant recipients, and to determine if persistence of EBV DNAemia can predict excessive immunosuppression as indicated by the incidence of infections requiring hospitalisation, EBV driven PTLD and mortality.

Official Title
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EVITA Study - Epstein-Barr Virus Infection moniToring in renAl Transplant Recipients - Early Identification of Increased Risk of Infection and Cancer for Individualised Immunosuppression.

Conditions
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EBV Infection, EBV Viremia, Epstein-Barr Virus Associated Lymphoproliferative Disorder, Post-transplant Lymphoproliferative Disorder

Intervention / Treatment
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* Diagnostic Test: EBV DNA in whole blood and plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children from 2 years of age receiving a kidney transplant from a living or deceased donor. Adults 18 years or older who receive a kidney transplant from a living or deceased donor. Capable of giving written informed consent to participation in the study (legal guardians capable of giving written informed consent to participation in the study in case of children younger than 18 years old). Exclusion Criteria: Patients unable to comply with the study requirements. Withdrawal of consent.

Ages Eligible for Study
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Minimum Age: 2 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 |
| --- | --- |
| Kidney transplant recipients<br>Adults and children undergoing kidney transplantation in Norway and the western part of Denmark. | Diagnostic Test: EBV DNA in whole blood and plasma<br>* Consecutive measurements of EBV DNA in whole blood and plasma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of EBV driven PTLD | The incidence rate of EBV driven PTLD in patients with and without 2 consecutive positive PCR samples for EBV DNA in whole blood and/or plasma during follow up (persistent EBV DNAemia). The detection level for EBV DNA in the whole blood is 110 IU/ml. Levels of EBV DNA < 1000 IU/ml are not quantified. The lower limit of detection for the EBV DNA plasma analysis is 25 IU/ml. Levels of EBV < 100 IU/ml are not quantified | 2 years | 
| The incidence rate of infections requiring hospitalisation in patients with and without persistant EBV DNAemia | The incidence rate of infections requiring hospitalisation in patients with and without 2 consecutive positive PCR samples for EBV DNA in whole blood and/or plasma during follow up (persistent EBV DNAemia). | 2 years | 
| Mortality rate in patients with and without persistant EBV DNAemia | Mortality rate in patients with and without 2 consecutive positive PCR samples for EBV DNA in whole blood and/or plasma during follow up (persistent EBV DNAemia). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of symptomatic opportunistic infections | Defined as CMV, BK virus, Herpes simplex virus 1 and 2, Human herpes virus 6 and 7, and Varicella zoster virus. In addition, bacterial pathogens such as Legionella pneumophila, Listeria monocytogenes, Mycobacterium tuberculosis, Nocardia, all parasitic infections i.e. Pneumocystis jirovecii and fungal infections are regarded as opportunistic infections. | 2 years | 
| Incidence of infections requiring hospitalisation |  | 2 years | 
| Incidence of EBV driven PTLD during follow-up. | PTLD verified by a biopsy. Cases of PTLD will be reviewed according to the WHO-definitions | 2 years | 
| Incidence of acute rejection | The incidence of acute rejection and chronic graft changes will be evaluated according to the Banff classification system. Cases without a biopsy will be registered if they have been treated as a an acute rejection | 2 years | 
| Kidney graft function | Kidney graft function at 2, 6, 12 and 24 months after transplantation will be evaluated by estimated glomerular filtration rate (eGFR, mL/min.) and urine albumin/creatinine | 2 years |