Cytomegalovirus InfectionsNCT03858907
Cytomegalovirus Risk in Seropositive Kidney Transplant Recipients Stratified by Quantiferon-CMV
An observational study of Cytomegalovirus Infections and CMV, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial 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"). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections, CMV, Kidney Transplant Infection
- How many people
- 180 participants
- Where
- 1 siteBrazil
- Study dates
- 5 Aug 2018to 30 Nov 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Kidney transplant recipients from a big tertiary hospital in Sao Paulo, Brazil
Who may be able to join
- CMV IgG seropositivity before kidney transplant
- to provide signed Informed Consent
Who cannot join
- death or graft failure before day 19 post-transplant
- allergy to valganciclovir ou ganciclovir
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital das Clinicas, University of Sao Paulo School of MedicinE
São Paulo, São Paulo, 05403-900
Ligia Pierrotti, MD, PhD, +551126618089, pierrotti@usp.br
About this study
Official title: 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.
Read the 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.
- Conditions
- Cytomegalovirus Infections, CMV, Kidney Transplant Infection
- Medical subject headings
- Cytomegalovirus Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
CMV disease/treated infection occurrence according to Quantiferon-CMV result
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
Measured: 365 days
Secondary outcomes (7)
QF-CMV cutoff values
To define cut-off values of IFN-gamma production by Quantiferon-CMV that best predict CMV (disease or treated viremia) occurrence
Measured: 365 days
CMV risk prediction index
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).
Measured: 365 days
Association of CMV with clinical events
To evaluate the association of CMV infection with occurrence: acute rejection, bacterial or opportunistic infection and neutropenia
Measured: 365 days
Association of CMV and patient and graft survivals
To analyze patient and graft survival stratified by CMV infection (Kaplan-Meier method)
Measured: 365 days
Association of CMV and total IgG levels
To evaluate the association of CMV infection with serum IgG (immunoglobulin G) levels at 0, 1, 3, and 6 months post-transplant
Measured: 365 days
Association of CMV and lymphocytes counts
To evaluate the association of CMV infection with blood CD4 and CD8 lymphocytes counts at 0, 1, 3, and 6 months post-transplant
Measured: 365 days
Association of CMV and graft function
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
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start5 Aug 2018
- Primary completion5 Aug 2020 (estimated)
- Study completion30 Nov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elias David-Neto, MD, PhD, Principal investigator, Instituto do Coracao
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03858907
- Sponsor's protocol ID
- quantiferon-cmv_ktx
- Status last verified
- Feb 2019
- First submitted
- 21 Feb 2019
- Last updated
- 1 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Reusing JO Jr, Feitosa EB, Agena F, Pierrotti LC, Azevedo LSF, Kotton CN, David-Neto E. Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease. Transpl Infect Dis. 2018 Oct;20(5):e12929. doi: 10.1111/tid.12929. Epub 2018 Jul 2.
PubMed 29809309Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.
PubMed 29596116David-Neto E, Triboni AH, Paula FJ, Vilas Boas LS, Machado CM, Agena F, Latif AZ, Alencar CS, Pierrotti LC, Nahas WC, Caiaffa-Filho HH, Pannuti CS. A double-blinded, prospective study to define antigenemia and quantitative real-time polymerase chain reaction cutoffs to start preemptive therapy in low-risk, seropositive, renal transplanted recipients. Transplantation. 2014 Nov 27;98(10):1077-81. doi: 10.1097/TP.0000000000000189.
PubMed 24839894Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation. 2012 Jan 27;93(2):195-200. doi: 10.1097/TP.0b013e31823c1cd4.
PubMed 22179399Fernandez-Ruiz M, Gimenez E, Vinuesa V, Ruiz-Merlo T, Parra P, Amat P, Montejo M, Paez-Vega A, Cantisan S, Torre-Cisneros J, Fortun J, Andres A, San Juan R, Lopez-Medrano F, Navarro D, Aguado JM; Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI). Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment. Clin Microbiol Infect. 2019 Mar;25(3):381.e1-381.e10. doi: 10.1016/j.cmi.2018.05.010. Epub 2018 May 25.
PubMed 29803844Cantisan S, Lara R, Montejo M, Redel J, Rodriguez-Benot A, Gutierrez-Aroca J, Gonzalez-Padilla M, Bueno L, Rivero A, Solana R, Torre-Cisneros J. Pretransplant interferon-gamma secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation. Am J Transplant. 2013 Mar;13(3):738-45. doi: 10.1111/ajt.12049. Epub 2013 Jan 11.
PubMed 23311355Gibson L. An Interferon-gamma Release Assay for Evaluation of Cell-mediated Immunity in Infants With Congenital Cytomegalovirus Infection. Clin Infect Dis. 2021 Aug 2;73(3):374-375. doi: 10.1093/cid/ciaa700. No abstract available.
PubMed 32504089
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Cytomegalovirus Disease or High Viremia in Seropositive Kidney Transplant Recipients Stratified by Quantiferon-CMV
- ClinicalTrials.gov ID
- NCT03858907
- Acronym / sponsor ID
- quantiferon-cmv_ktx
- Conditions
- Cytomegalovirus Infections, CMV, Kidney Transplant Infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- 5 Aug 2018 (actual)
- Primary completion
- 5 Aug 2020 (estimated)
- Study completion
- 30 Nov 2020 (estimated)
- First posted
- 1 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Kidney transplant recipients from a big tertiary hospital in Sao Paulo, Brazil
Key inclusion criteria (2 listed)
- CMV IgG seropositivity before kidney transplant
- to provide signed Informed Consent
Key exclusion criteria (2 listed)
- death or graft failure before day 19 post-transplant
- allergy to valganciclovir ou ganciclovir
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
7 secondary outcomes
QF-CMV cutoff values
Time frame: 365 days
CMV risk prediction index
Time frame: 365 days
Association of CMV with clinical events
Time frame: 365 days
Association of CMV and patient and graft survivals
Time frame: 365 days
Association of CMV and total IgG levels
Time frame: 365 days
Association of CMV and lymphocytes counts
Time frame: 365 days
Association of CMV and graft function
Time frame: 365 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2019.
- Background: PubMed 29809309Reusing JO Jr, Feitosa EB, Agena F, Pierrotti LC, Azevedo LSF, Kotton CN, David-Neto E. Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease. Transpl Infect Dis. 2018 Oct;20(5):e12929. doi: 10.1111/tid.12929. Epub 2018 Jul 2.
- Background: PubMed 29596116Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.
- Background: PubMed 24839894David-Neto E, Triboni AH, Paula FJ, Vilas Boas LS, Machado CM, Agena F, Latif AZ, Alencar CS, Pierrotti LC, Nahas WC, Caiaffa-Filho HH, Pannuti CS. A double-blinded, prospective study to define antigenemia and quantitative real-time polymerase chain reaction cutoffs to start preemptive therapy in low-risk, seropositive, renal transplanted recipients. Transplantation. 2014 Nov 27;98(10):1077-81. doi: 10.1097/TP.0000000000000189.
- Background: PubMed 22179399Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation. 2012 Jan 27;93(2):195-200. doi: 10.1097/TP.0b013e31823c1cd4.
- Background: PubMed 29803844Fernandez-Ruiz M, Gimenez E, Vinuesa V, Ruiz-Merlo T, Parra P, Amat P, Montejo M, Paez-Vega A, Cantisan S, Torre-Cisneros J, Fortun J, Andres A, San Juan R, Lopez-Medrano F, Navarro D, Aguado JM; Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI). Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment. Clin Microbiol Infect. 2019 Mar;25(3):381.e1-381.e10. doi: 10.1016/j.cmi.2018.05.010. Epub 2018 May 25.
- Background: PubMed 23311355Cantisan S, Lara R, Montejo M, Redel J, Rodriguez-Benot A, Gutierrez-Aroca J, Gonzalez-Padilla M, Bueno L, Rivero A, Solana R, Torre-Cisneros J. Pretransplant interferon-gamma secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation. Am J Transplant. 2013 Mar;13(3):738-45. doi: 10.1111/ajt.12049. Epub 2013 Jan 11.
- Derived from this study: PubMed 32504089Gibson L. An Interferon-gamma Release Assay for Evaluation of Cell-mediated Immunity in Infants With Congenital Cytomegalovirus Infection. Clin Infect Dis. 2021 Aug 2;73(3):374-375. doi: 10.1093/cid/ciaa700. No abstract available.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elias David-Neto, MD, PhD principal investigator
Instituto do Coracao
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Infections and CMV, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jose O Reusing Junior, MD (+551126618089, jotto@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CMV disease/treated infection occurrence according to Quantiferon-CMV result (time frame: 365 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03858907, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2019.