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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Post-transplant Lymphoproliferative Disorder; EBV Infection; EBV Viremia; Epstein-Barr Virus Associated Lymphoproliferative Disorder
• Intervention / Treatment: Diagnostic test: EBV DNA in whole blood and plasma

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Lene Ludvigsen, MD; Phone Number: 78450000; Email: Lene.Ugilt@auh.rm.dk
• Study Contact Backup: Name: Bente Jespersen, Professor

Study Locations

• Denmark
  • Central Region Denmark
    • Aarhus, Central Region Denmark, Denmark
      • Recruiting
      • Aarhus University Hospital
      • Contact: Bente Jespersen, Professor
      • Contact: Lene Ludvigsen, MD; Email: lene.ugilt@auh.rm.dk
  • Region Of Southern Denmark
    • Odense, Region Of Southern Denmark, Denmark
      • Active, not recruiting
      • Odense University Hospital
• Norway
  • Oslo, Norway
    • Recruiting
    • Rikshospitalet, Oslo Universitetssykehus
    • Contact: Anna Reisæter, MD, DMSc; Email: areisate@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Consecutive measurements of EBV DNA in whole blood and plasma

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Rikshospitalet University Hospital
• Investigators: Principal Investigator: Bente Jespersen, Professor, Aarhus University Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; DNA Virus Infections; Sepsis; Tumor Virus Infections; Herpesviridae Infections; Disease; Infections; Communicable Diseases; Virus Diseases; Viremia; Epstein-Barr Virus Infections; Lymphoproliferative Disorders
• Other Study ID Numbers: EBV Renal

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No