Natural History of Cytomegalovirus (CMV) Infection and Disease Among Renal Transplant Recipients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Hospital do Rim e Hipertensão
Sponsor:
Information provided by (Responsible Party):
Helio Tedesco Silva Junior, Hospital do Rim e Hipertensão
ClinicalTrials.gov Identifier:
NCT01833416
First received: March 7, 2013
Last updated: June 28, 2013
Last verified: June 2013
  Purpose

Although the accumulated knowledge regarding Cytomegalovirus (CMV) infection increased substantially over the past years, several issues still deserve further investigation. The epidemiology of this disease has been changing, perhaps influenced by new immunosuppressive strategies currently used and growing and widespread use of prophylaxis. The knowledge of the CMV viral load kinetics, using a polymerase chain reaction (PCR-based assay), among renal transplant recipients not receiving any prophylactic therapy will allow the determination of risk factors for and the impact of earlier intervention on CMV infection and disease. The goal is to ultimately improve the clinical outcomes for renal transplant recipients.


Condition
Infection in Solid Organ Transplant Recipients

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History of Cytomegalovirus (CMV) Infection and Disease Among Renal Transplant Recipients

Resource links provided by NLM:


Further study details as provided by Hospital do Rim e Hipertensão:

Primary Outcome Measures:
  • Incidence of cytomegalovirus(CMV)infection and disease among renal transplant recipients receiving preemptive therapy. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Change from baseline clinical and epidemiological aspects of CMV infection in this kidney transplant population. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Sorolical status CMV

  • Risk factors associated with prolonged treatment and recurrence of CMV infection or disease. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    • 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)


Estimated Enrollment: 150
Study Start Date: April 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

All male and female de novo kidney transplant recipients

Criteria

Inclusion Criteria:

  1. Informed consent.
  2. Male/female patients at least 18 years old who will be followed at our outpatient clinic for at least one year.
  3. Recipients of first or repeat kidney transplants from living or deceased donors.

Exclusion Criteria:

  1. Recipients of any combined transplant (kidney/pancreas, kidney liver).
  2. Unlikely to comply with the requirements of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01833416

Contacts
Contact: Helio T Silva-Junior, MD 55 11 5087-8110 heliotedesco@medfarm.com.br
Contact: Claudia R Felipe, PharmD 55 11 5087-8318 claudiafelipe@medfarm.com.br

Locations
Brazil
Hospital do Rim e Hipertensao Recruiting
Sao Paulo, Brazil, 04038002
Contact: Helio T Silva-Junior, MD    55 11 5087-8113    heliotedesco@medfarm.com.br   
Contact: Claudia R Felipe, PharmD    55 11 5087-8318    claudiafelipe@medfarm.com.br   
Sponsors and Collaborators
Helio Tedesco Silva Junior
Investigators
Principal Investigator: Helio T Silva-Junior, MD Hospital do Rim e Hipertensao
  More Information

No publications provided

Responsible Party: Helio Tedesco Silva Junior, PhD, Hospital do Rim e Hipertensão
ClinicalTrials.gov Identifier: NCT01833416     History of Changes
Other Study ID Numbers: 2013027692
Study First Received: March 7, 2013
Last Updated: June 28, 2013
Health Authority: Brazil: Associação Fundo de Incentivo à Pesquisa

Keywords provided by Hospital do Rim e Hipertensão:
CMV infection
CMV disease
Natural history
Kidney transplant

Additional relevant MeSH terms:
Infection
Communicable Diseases

ClinicalTrials.gov processed this record on September 16, 2014