ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01972035
First received: October 10, 2013
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

Our study will compare adult kidney transplant recipients receiving valganciclovir vs. valacyclovir for one year following kidney transplant and compare:

  1. the incidence
  2. duration of CMV and EBV viremia and
  3. the magnitude of viremia measured by area under the viral load-time curve (AUC) of recipients who become viremic with CMV and/or EBV.

In addition, we will test renal tissue obtained from adult protocol biopsies at the time of kidney transplant and 3 and 12 months post-transplant by both polymerase chain reaction (PCR) and fluorescence in situ hybridization to assess for latent CMV and/or EBV.


Condition Intervention Phase
Kidney Transplantation
Epstein-Barr Virus Infections/Complications
Cytomegalovirus Infections/Complications
Drug: Valacyclovir
Drug: Valganciclovir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Change in incidence and magnitude of CMV and EBV viremia in kidney transplant [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    In infectious mononucleosis intervention trials, two weeks of valA therapy resulted in a statistically significant reduction in oral EBV shedding, accompanied by a clinical benefit, and valA is currently used for the therapy of severe cases of infectious mononucleosis in the community. ValA has also been shown to reduce the incidence and delay the onset of CMV disease in both CMV seronegative patients (P<0.001) and CMV seropositive patients (P=0.03). Therefore we hypothesize that the anti-EBV and anti-CMV effects of valA will be equal to or more effective than valG in reducing post-kidney transplant EBV and CMV viremia.


Secondary Outcome Measures:
  • Change in number of dose-limiting side effects in kidney transplant recipients receiving valA vs. valG. [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    ValG is associated with adverse events including diarrhea, fever, nausea, vomiting, tremor, leucopenia, neutropenia, anemia and thrombocytopenia in ≥20% of patients. ValG induced leucopenia often necessitates a reduction in immunosuppressive therapy, increasing the risk of allograft rejection. Fewer severe adverse events are related to valA, including rash (8%), abdominal pain (1% to 11%), nausea (5% to 15%), vomiting (less than 1% to 6%), headache (13% to 38%) and fatigue (8%). Very high doses of valA (8g/day) for post-kidney transplant CMV prophylaxis was shown to have no severe or treatment-limiting side effects compared to placebo. Therefore we anticipate that the proportion of patients requiring dose reduction or cessation of valA vs. valG due to adverse drug side effects will be less.

  • To identify the presence and quantity of EBV and CMV in renal tissue biopsies from kidney transplant recipients. [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    It is postulated that latent virus in renal tissue is a major source of post-kidney transplant recipient infection, but this remains unproven. The ability in this research study to test renal tissue obtained from adult protocol biopsies at the time of kidney transplant and 3 and 12 months post-kidney transplant (corresponding with the timing of routine surveillance post-kidney transplant biopsies) by both polymerase chain reaction (PCR) and fluorescence in situ hybridization provides a unique opportunity to test this.


Estimated Enrollment: 30
Study Start Date: July 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ValAcyclovir
Kidney recipients who give informed consent will be randomly assigned to receive ValA or ValG in a 1:1 ratio. Duration of therapy is 3-6 months and dosing is based on glomerular filtration rate.
Drug: Valacyclovir
Experimental Arm
Other Names:
  • Valtrex
  • Valacyclovir Hydrochloride
  • Valacyclovir HCL
Active Comparator: ValGanciclovir
Kidney recipients who give informed consent will be randomly assigned to receive ValG or ValA in a 1:1 ratio. Duration of therapy is 3-6 months and dosing is based on glomerular filtration rate
Drug: Valganciclovir
Current standard of care
Other Names:
  • Valcyte
  • Valganciclovir hydrochloride

Detailed Description:

Herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) cause considerable morbidity and mortality post-kidney transplant. Even subclinical CMV and/or EBV viremia have been associated with deterioration in kidney transplant function. Currently, valganciclovir (valG) is the primary prophylactic agent against CMV in kidney transplant recipients but CMV viremia has been noted in 22% of pediatric post-kidney transplant recipients, and the incidence at the University of Minnesota (UMMC) in all kidney transplant recipients is as high as 17% despite valG prophylaxis. CMV disease post-kidney transplant can manifest as fever, leucopenia, or mild to severe organ involvement. While an effective anti-CMV drug, valG has a number of adverse effects including leucopenia, also a side effect of mycophenolate mofetil (MMF), one of the cornerstones of current anti-rejection regimens. Combined therapy with MMF and valG frequently results in leucopenia associated infection or leucopenia necessitating reduction in MMF doses, increasing the risk of rejection. In addition, valG is prohibitively expensive forcing many centers adopt a pre-emptive therapeutic approach whereby post-Ktx patients are screened for CMV, and at new onset viremia, valG is initiated. This approach has been associated with increased CMV infections and resistant viral strains. Therefore, there is need for an alternate, more cost-effective drug with a more benign side effect profile and equal effectiveness against CMV.

To date, the anti-EBV effect of valG is poorly defined and prevention of EBV infection is by close monitoring and immunosuppression reduction at the discovery of EBV viremia. EBV can present post-kidney transplants as infectious mononucleosis syndrome, hepatitis and, most importantly, can initiate potentially fatal lymphoproliferative disorders (PTLD). Between October 2003 and December 2009, EBV viremia occurred in 20% of adults and 50% of pediatric kidney transplant recipients (60/120) at UMMC, and, PTLD occurred in 6% (7/120) of pediatric recipients. Effective anti-EBV prophylaxis could substantially improve kidney transplant outcomes.

UMMC conducts surveillance biopsies at transplant and 3 and 12 months post-kidney transplant on all adult transplant recipients, providing an ideal opportunity to assess kidney tissue for EBV and CMV via molecular and immunological assays. Isolating the virus from infected recipient would be a pivotal step in our understanding of the mechanisms of CMV and EBV infection post-kidney transplant.

In summary, if valA and valG have equivalent efficacy in CMV prophylaxis, and valA has the anticipated effect on EBV prevention, the use of valA will result in a reduced risk of leucopenia-associated infection, and a lower incidence of rejection by allowing the use of standard MMF doses. Since valA is cheaper, it is plausible that universal prophylaxis will be a plausible and affordable option for all transplant recipients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All consenting adult primary kidney transplant recipients who are preferably seronegative for CMV/EBV with a donor who is correspondingly seropositive for the same virus.

Exclusion Criteria:

  • Non-consent.
  • Recipient age <18 years.
  • Recipients that are unable to independently understand the consent form and do not have a legally authorized representative.
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01972035     History of Changes
Other Study ID Numbers: 1307M37702
Study First Received: October 10, 2013
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
EBV
CMV
Kidney transplant
valganciclovir
valacyclovir

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Cytomegalovirus Infections
Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Neoplasms, Experimental
Neoplasms
Valacyclovir
Acyclovir
Valganciclovir
Ganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014