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

NCT04189835 | Completed

• 1 other identifier: EBV Renal
• Study Type: observational
• Target: 509
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• The incidence rate of EBV driven PTLD

  The incidence rate of EBV driven PTLD in patients with 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 persistant EBV DNAemia

  The incidence rate of infections requiring hospitalisation in patients with 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 persistant EBV DNAemia

  Mortality rate in patients with 2 consecutive positive PCR samples for EBV DNA in whole blood and/or plasma during follow up (persistent EBV DNAemia).

  2 years

Secondary Outcomes (5)

• The incidence of symptomatic opportunistic infections

  2 years

• Incidence of infections requiring hospitalisation

  2 years

• Incidence of EBV driven PTLD during follow-up.

  2 years

• Incidence of acute rejection

  2 years

• Kidney graft function

  2 years

Study Arms (1)

Kidney transplant recipients

Adults and children undergoing kidney transplantation in Norway and the western part of Denmark.

Diagnostic Test: EBV DNA in whole blood and plasma

Interventions

EBV DNA in whole blood and plasma DIAGNOSTIC_TEST

Consecutive measurements of EBV DNA in whole blood and plasma

Kidney transplant recipients

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with end-stage renal disease in the southern part of Norway and in the western part of Denmark qualified to undergo kidney transplantation.

You may qualify if:

• 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).

You may not qualify if:

• Patients unable to comply with the study requirements.
• Withdrawal of consent.

Sponsors & Collaborators

• University of Aarhus: lead
• Rikshospitalet University Hospital: collaborator
• Aarhus University Hospital: collaborator
• Odense University Hospital: collaborator

Study Sites (3)

Aarhus University Hospital

Aarhus, Central Region Denmark, Denmark

Location

Odense University Hospital

Odense, Region Syddanmark, Denmark

Location

Rikshospitalet, Oslo Universitetssykehus

Oslo, Norway

Location

Related Publications (3)

• Wareham NE, Mocroft A, Sengelov H, Da Cunha-Bang C, Gustafsson F, Heilmann C, Iversen M, Kirkby NS, Rasmussen A, Sorensen SS, Lundgren JD; MATCH in PERSIMUNE study group. The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients. J Cancer Res Clin Oncol. 2018 Aug;144(8):1569-1580. doi: 10.1007/s00432-018-2674-9. Epub 2018 May 26.

  PMID: 29804164 BACKGROUND

• Allen UD, Preiksaitis JK; AST Infectious Diseases Community of Practice. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13652. doi: 10.1111/ctr.13652. Epub 2019 Jul 23.

  PMID: 31230381 BACKGROUND

• San-Juan R, Manuel O, Hirsch HH, Fernandez-Ruiz M, Lopez-Medrano F, Comoli P, Caillard S, Grossi P, Aguado JM; ESGICH PTLD Survey Study Group,; European Study Group of Infections in Compromised Hosts (ESGICH) from the European Society of Microbiology and Infectious Diseases (ESCMID). Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey. Clin Microbiol Infect. 2015 Jun;21(6):604.e1-9. doi: 10.1016/j.cmi.2015.02.002. Epub 2015 Feb 14.

  PMID: 25686696 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, whole blood and tissue biopsies.

MeSH Terms

Conditions

Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Bente Jespersen, Professor

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: December 6, 2019
• Study Start: January 3, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2); NO (1)