Clinical trial NCT04189835: EVITA Study - Epstein-Barr Virus Infection MoniToring in RenAl Transplant Recipients
Official title: EVITA Study - Epstein-Barr Virus Infection MoniToring in RenAl Transplant Recipients - Early Identification of Increased Risk of Infection and Cancer for Individualised Immunosuppression.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: EBV Infection
EBV Viremia
Epstein-Barr Virus Associated Lymphoproliferative Disorder
Post-transplant Lymphoproliferative Disorder
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Rikshospitalet University Hospital
name: Aarhus University Hospital
name: Odense University Hospital
First posted: 2019-12-06
Enrollment: 509
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The incidence rate of EBV driven PTLD
timeFrame: 2 years
measure: The incidence rate of infections requiring hospitalisation in patients with persistant EBV DNAemia
timeFrame: 2 years
measure: Mortality rate in patients with persistant EBV DNAemia
timeFrame: 2 years
Secondary outcomes:
measure: The incidence of symptomatic opportunistic infections
timeFrame: 2 years
measure: Incidence of infections requiring hospitalisation
timeFrame: 2 years
measure: Incidence of EBV driven PTLD during follow-up.
timeFrame: 2 years
measure: Incidence of acute rejection
timeFrame: 2 years
measure: Kidney graft function
timeFrame: 2 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Central Region Denmark
city: Odense
country: Denmark
facility: Odense University Hospital
state: Region of Southern Denmark
city: Oslo
country: Norway
facility: Rikshospitalet, Oslo Universitetssykehus
Study officials:
affiliation: Aarhus University Hospital
name: Bente Jespersen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.