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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
Sponsor:
Information provided by (Responsible Party):
University of Sao Paulo General Hospital

Study Description
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Brief Summary:
To evaluate the Quantiferon-CMV test ability to predict occurrence of cytomegalovirus (CMV) disease o treated infection after kidney transplantation. Patients studied are those already infected by CMV before transplantation ("seropositive"). Patients given thymoglobulin as induction therapy receive CMV prophylaxis with valganciclovir, while those given basiliximab undergo weekly monitoring for CMV viremia with preemptive treatment as needed.

Condition or disease
Cytomegalovirus Infections CMV Kidney Transplant Infection

Detailed Description:

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 Design
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Study Type : Observational
Estimated Enrollment : 180 participants
Observational Model: Cohort
Time Perspective: Prospective
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

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Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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).

  3. 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

  4. 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)

  5. 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

  6. 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

  7. 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


Other Outcome Measures:
  1. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Kidney transplant recipients from a big tertiary hospital in Sao Paulo, Brazil
Criteria

Inclusion Criteria:

  • CMV IgG seropositivity before kidney transplant
  • to provide signed Informed Consent

Exclusion Criteria:

  • death or graft failure before day 19 post-transplant
  • allergy to valganciclovir ou ganciclovir
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03858907


Contacts
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Contact: Jose O Reusing Junior, MD +551126618089 jotto@usp.br
Contact: Fabiana Agena, N +551126618089 fabiana.agena@hc.fm.usp.br

Locations
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Brazil
Hospital das Clinicas, University of Sao Paulo School of MedicinE Recruiting
Sao Paulo, SP, Brazil, 05403-900
Contact: Ligia Pierrotti, MD, PhD    +551126618089    pierrotti@usp.br   
Sponsors and Collaborators
University of Sao Paulo General Hospital
Investigators
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Principal Investigator: Elias David-Neto, MD, PhD Instituto do Coracao
More Information
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Publications:

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Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT03858907    
Other Study ID Numbers: quantiferon-cmv_ktx
First Posted: March 1, 2019    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Cytomegalovirus Infections
 Herpesviridae Infections
DNA Virus Infections
Virus Diseases