Natural History of Cytomegalovirus (CMV) Infection and Disease Among Renal Transplant Recipients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01833416|
Recruitment Status : Completed
First Posted : April 16, 2013
Last Update Posted : March 23, 2015
|Condition or disease|
|Infection in Solid Organ Transplant Recipients|
Cytomegalovirus (CMV) infection remains one of the most common complications affecting organ transplant recipients, with significant morbidity and occasional mortality. The adverse impact of CMV infection on graft function underscores the importance of CMV on transplant outcomes.
CMV prevention strategies have resulted in significant reductions in CMV disease and CMV-related mortality. The reduction in the incidence of "indirect effects" of CMV infection has also been attributed to the use of CMV prevention. Nevertheless, management of CMV infection varies considerably among transplant centers. Two major strategies are commonly used for prevention of CMV: universal prophylaxis and preemptive therapy. Within each of these strategies, significant variation in clinical practice exists, including type of cellular or molecular diagnostics, antiviral therapies, monitoring and criteria for stopping treatment.
Although the use of universal prophylaxis has increased since the availability of valganciclovir, there is still a debate regarding the superiority of this strategy over the preemptive approach. Furthermore, this costly therapy or any other CMV prophylaxis is currently not reimbursed by our unified public health system. Therefore our strategy has been to use preemptive therapy. Additionally, because we consider different immunosuppressive regimens according to pretransplant stratified evaluation of risk of rejection, only kidney transplant recipients at high risk to develop CMV infection or disease, i.e., negative recipients of positive organ donors, patients receiving induction therapy with thymoglobulin and patients treated for acute rejection undergo preemptive strategy. Using this strategy, our currently overall incidence of CMV infection or disease is currently 25%. This incidence is higher among recipients who received thymoglobulin induction, tacrolimus and mycophenolate maintenance combination or treatment for acute rejection with either high dose of corticosteroids or thymoglobulin.
Because none of the kidney transplant recipients at our institution receive any prophylaxis for CMV infection and because immunosuppressive regimens are selected according to immunological rejection risk, this is the ideal population to investigate the natural history of CMV infection and disease using more recent, sensitive and specific molecular tolls.
|Study Type :||Observational|
|Actual Enrollment :||150 participants|
|Official Title:||Natural History of Cytomegalovirus (CMV) Infection and Disease Among Renal Transplant Recipients|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||June 2014|
- Incidence of cytomegalovirus(CMV)infection and disease among renal transplant recipients receiving preemptive therapy. [ Time Frame: 3 months ]There is still a debate regarding the superiority strategy with valganciclovir over the preemptive approach. Furthermore, this costly therapy or any other CMV prophylaxis is currently not reimbursed by our unified public health system. Therefore our strategy has been to use preemptive therapy.
- Change from baseline clinical and epidemiological aspects of CMV infection in this kidney transplant population. [ Time Frame: 3 months ]
Within each of these strategies, significant variation in clinical practice exists, including type of cellular or molecular diagnostics, antiviral therapies, monitoring and criteria for stopping treatment.We estimate that approximately 200 patients will be enrolled for this research. For this assessment we use monitoring for CMV replication:
Samples will be collected every week for up to 3 months for determination of antigenemia and viral load. Investigators will be blinded to the results of the PCR analyses, unless unblinding is clinically indicated.
Antigenemia test: Method: Antigen pp65 by indirect immunofluorescence. Reference: Zero Positive Cells /200.000 cells.
Viral load test: Method: Real Time PCR - TaqMan Result: < 50 copies/mL Log: < 1.70 Detection Limit: 50 copies/mL Observations: Viral loads above 100 copies/mL should be considered active replication. Range of 50 to 109 copies/ml.
- Incidence of the CMV viral load kinetics using a PCR-based assay among renal transplant recipients. [ Time Frame: 3 months ]Questions include: (a) when after transplant is CMV viral load first detected; (b) how rapidly does viral load increase over time; and (c) what percent of patients with a detectable CMV viral load will develop a detectable CMV antigen.
- The ideal time to start preemptive anti-CMV therapy. [ Time Frame: 3 months ]Starting preemptive anti-CMV therapy based on viral load data. A question to consider is whether an absolute CMV viral load or a rate of change in the CMV.
- Baseline factors that can predict those patients at risk for developing a CMV viral load parameter that correlates with development of a detectable CMV antigen. [ Time Frame: 3 months ]Sorolical status CMV
- Risk factors associated with prolonged treatment and recurrence of CMV infection or disease. [ Time Frame: 3 months ]
- Patients who have the serological status negative for cmv and received a kidney transplant from a donor with positive serology
- Patients who underwent treatment for acute rejection
- Patients who used thymoglobulin (induction and /or treatment of acute rejection)
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): NCT01833416
|Hospital do Rim e Hipertensao|
|Sao Paulo, Brazil, 04038002|
|Principal Investigator:||Helio T Silva-Junior, MD||Hospital do Rim e Hipertensao|