Cytomegalovirus Risk in Seropositive Kidney Transplant Recipients Stratified by Quantiferon-CMV
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|ClinicalTrials.gov Identifier: NCT03858907|
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : March 1, 2019
|Condition or disease|
|Cytomegalovirus Infections CMV Kidney Transplant Infection|
This study evaluates Quantiferon-CMV assay ability for CMV (cytomegalovirus) risk prediction in kidney transplant recipients. Quantiferon-Monitor ability to predict infection or graft rejection will be evaluated as an exploratory objective.
It is a prospective cohort study. The assumption is that CMV disease or preemptively treated viremia (dependent variable) may be predicted by Quantiferon-CMV result (independent variable). Quantiferon-CMV results will be masked for the assistant physician.
Patients are evaluated for eligibility on their hospital admission for kidney transplantation. Type of induction therapy follows current local protocol: thymoglobulin is given to sensitized patients against HLA - human leukocyte antigen (that is, PRA > 0%), and basiliximab to unsensitized patients (PRA = 0%). Initial maintenance immunosuppression includes prednisone, tacrolimus and mycophenolate sodium to all patients. If a patient is enrolled in the study, blood is drawn before transplantation for pre-transplant Quantiferon assays (CMV and Monitor).
For CMV disease prevention, transplant recipients undergo until day 90 post-transplant: either weekly CMV monitoring (qPCR - quantitative polymerase chain reaction - and pp65 antigenemia) and preemptive treatment if given basiliximab or antiviral prophylaxis if given thymoglobulin for induction. Cutoff values for preemptive treatment are 4,000 IU/ml of plasma for Abbott Real Time PCR or ≥ 4 cells/300.000 neutrophils for pp65 Antigenemia. After day 90 post-transplant, all participants undergo biweekly CMV monitoring until day 180 with preemptive treatment as needed.
Quantiferon-CMV results from 2 or 3 different moments (pre-transplant, day 30 and for patients given thymoglobulin also day 90) will be analyzed with subsequent occurrence of CMV disease/treated viremia. Analysis will be stratified by type of induction therapy. A high negative predictive value of pre-transplant or day 30 Quantiferon-CMV could indicate unneeded monitoring for preemptive treatment. On the other hand, a high positive predictive value for CMV occurrence could indicate the necessity of antiviral prophylaxis implementation.
Patients given thymoglobulin will undergo a third Quantiferon-CMV on day 90, at the end of their antiviral prophylaxis. This third Quantiferon-CMV may predict occurrence of late disease, together with clinical variables (low kidney graft function / glomerular filtration rate, lymphopenia or type of donor). A high positive predictive value for CMV disease/treated viremia could indicate the need for antiviral extension beyond 3 months.
Clinical and laboratory parameters evaluated also include: demographic and pre-transplant clinical data, monthly creatinine and blood cell counts, complement 3 fraction, total IgG, blood BK and EBV virus qPCR, CD4/CD8 cells counts, CMV serology, acute rejection and type of treatment, opportunistic and bacterial infections, post-transplant diabetes, maintenance immunosuppression, diabetes, delayed graft-function.
Multivariable logistic regression models will be tested for their performance to predict CMV disease/treated infection.
For the cost-effectiveness analysis, current strategy without QF-CMV will be compared with a simulated strategy with a QF-CMV-oriented CMV prevention. For this analysis, costs will be in the perspective of Hospital das Clinicas de Sao Paulo with values obtained part from micro-costing and part from secondary data.
|Study Type :||Observational|
|Estimated Enrollment :||180 participants|
|Official Title:||Risk of Cytomegalovirus Disease or High Viremia in Seropositive Kidney Transplant Recipients Stratified by Quantiferon-CMV|
|Actual Study Start Date :||August 5, 2018|
|Estimated Primary Completion Date :||August 5, 2020|
|Estimated Study Completion Date :||November 30, 2020|
- CMV disease/treated infection occurrence according to Quantiferon-CMV result [ Time Frame: 365 days ]To evaluate if QF-CMV (either pre or post-transplant) predicts occurrence of CMV disease or treated infection in CMV seropositive kidney recipients, stratified by type of induction therapy
- QF-CMV cutoff values [ Time Frame: 365 days ]To define cut-off values of IFN-gamma production by Quantiferon-CMV that best predict CMV (disease or treated viremia) occurrence
- CMV risk prediction index [ Time Frame: 365 days ]To define the best predictive model for the occurrence of CMV, which includes QF-CMV and clinical/laboratory variables (donor type, kidney function and lymphocyte counts).
- Association of CMV with clinical events [ Time Frame: 365 days ]To evaluate the association of CMV infection with occurrence: acute rejection, bacterial or opportunistic infection and neutropenia
- Association of CMV and patient and graft survivals [ Time Frame: 365 days ]To analyze patient and graft survival stratified by CMV infection (Kaplan-Meier method)
- Association of CMV and total IgG levels [ Time Frame: 365 days ]To evaluate the association of CMV infection with serum IgG (immunoglobulin G) levels at 0, 1, 3, and 6 months post-transplant
- Association of CMV and lymphocytes counts [ Time Frame: 365 days ]To evaluate the association of CMV infection with blood CD4 and CD8 lymphocytes counts at 0, 1, 3, and 6 months post-transplant
- Association of CMV and graft function [ Time Frame: 365 days ]To evaluate the association of CMV infection with estimated glomerular filtration rate by Modification of Diet in Renal Disease formula (creatinine based) at 0, 1, 3, and 6 months post-transplant
- Infection and acute rejection prediction with Quantiferon-Monitor [ Time Frame: 365 days ]To evaluate the discriminative ability of QF-Monitor results (in IU of interferon/ml) to predict occurrence of first acute rejection episode or any bacterial/opportunistic infection
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03858907
|Contact: Jose O Reusing Junior, MDfirstname.lastname@example.org|
|Contact: Fabiana Agena, Nemail@example.com|
|Hospital das Clinicas, University of Sao Paulo School of MedicinE||Recruiting|
|Sao Paulo, SP, Brazil, 05403-900|
|Contact: Ligia Pierrotti, MD, PhD +551126618089 firstname.lastname@example.org|
|Principal Investigator:||Elias David-Neto, MD, PhD||Instituto do Coracao|