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

Post-transplant Lymphoproliferative Disorder Clinical Trial

— EVITA  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04189835
• Other study ID #: EBV Renal
• Status: Recruiting
• Start date: January 3, 2020
• Est. completion date: December 31, 2029

Study information

• Verified date: December 2022
• Source: University of Aarhus
• Contact: Lene Ludvigsen, MD
• Phone: 78450000
• Email: Lene.Ugilt[@]auh.rm.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2029
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Disease
• EBV Infection
• EBV Viremia
• Epstein-Barr Virus Associated Lymphoproliferative Disorder
• Epstein-Barr Virus Infections
• Infections
• Lymphoproliferative Disorders
• Post-transplant Lymphoproliferative Disorder
• Viremia
• Virus Diseases

Intervention

Diagnostic Test:
• EBV DNA in whole blood and plasma
Consecutive measurements of EBV DNA in whole blood and plasma

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus	Central Region Denmark
Denmark	Odense University Hospital	Odense	Region Of Southern Denmark
Norway	Rikshospitalet, Oslo Universitetssykehus	Oslo

Sponsors (4)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Odense University Hospital, Rikshospitalet University Hospital

Countries where clinical trial is conducted

Denmark,  Norway, 

References & Publications (3)

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. — View 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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	Incidence of infections requiring hospitalisation		2 years
Secondary	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
Secondary	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
Secondary	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