Cytomegalovirus Risk in Seropositive Kidney Transplant Recipients Stratified by Quantiferon-CMV

February 26, 2019 updated by: University of Sao Paulo General Hospital

Risk of Cytomegalovirus Disease or High Viremia in Seropositive Kidney Transplant Recipients Stratified by Quantiferon-CMV

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.

Study Overview

Status

Unknown

Conditions

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 Type

Observational

Enrollment (Anticipated)

180

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jose O Reusing Junior, MD
  • Phone Number: +551126618089
  • Email: jotto@usp.br

Study Contact Backup

Study Locations

  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 05403-900
        • Recruiting
        • Hospital das Clinicas, University of Sao Paulo School of MedicinE
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Kidney transplant recipients from a big tertiary hospital in Sao Paulo, Brazil

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
365 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
365 days
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).
365 days
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
365 days
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)
365 days
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
365 days
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
365 days
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
365 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
365 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Investigators

  • Principal Investigator: Elias David-Neto, MD, PhD, Instituto do Coracao

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 5, 2018

Primary Completion (ANTICIPATED)

August 5, 2020

Study Completion (ANTICIPATED)

November 30, 2020

Study Registration Dates

First Submitted

February 21, 2019

First Submitted That Met QC Criteria

February 26, 2019

First Posted (ACTUAL)

March 1, 2019

Study Record Updates

Last Update Posted (ACTUAL)

March 1, 2019

Last Update Submitted That Met QC Criteria

February 26, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • quantiferon-cmv_ktx

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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