ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease, Infectious Disease, Infectious Disease, Hospital |
| Therapuetic Areas: | Immunology / Infectious Diseases, Nephrology / Urology, Other |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 10/13/2018 |
| Start Date: | August 2014 |
| End Date: | July 2019 |
| Contact: | Amy Hanson |
| Email: | amhanson@umn.edu |
| Phone: | 612-626-4424 |
Our study will compare all kidney transplant recipients receiving valganciclovir vs.
valacyclovir for one year following kidney transplant and compare:
1. the incidence, magnitude and duration of CMV and EBV viremia in the first year after
transplant.
2. the side effects of the anti-viral drugs requiring dose reduction or cessation
In addition, we will test renal tissue obtained from any biopsies post-transplant
(surveillance or clinically indicated biopsies) by both polymerase chain reaction (PCR) and
fluorescence in situ hybridization to assess for latent CMV and/or EBV.
valacyclovir for one year following kidney transplant and compare:
1. the incidence, magnitude and duration of CMV and EBV viremia in the first year after
transplant.
2. the side effects of the anti-viral drugs requiring dose reduction or cessation
In addition, we will test renal tissue obtained from any biopsies post-transplant
(surveillance or clinically indicated biopsies) by both polymerase chain reaction (PCR) and
fluorescence in situ hybridization to assess for latent CMV and/or EBV.
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 valacyclovir and valganciclovir have equivalent efficacy in CMV prophylaxis,
and valacyclovir has the anticipated effect on EBV prevention, the use of valacyclovir 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 valacyclovir is cheaper, it is
plausible that universal prophylaxis will be a plausible and affordable option for all
transplant recipients.
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 valacyclovir and valganciclovir have equivalent efficacy in CMV prophylaxis,
and valacyclovir has the anticipated effect on EBV prevention, the use of valacyclovir 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 valacyclovir is cheaper, it is
plausible that universal prophylaxis will be a plausible and affordable option for all
transplant recipients.
Inclusion Criteria:
- All consenting kidney transplant recipients.
Exclusion Criteria:
- Non-consent.
- Recipients with allergies to valacyclovir or valganciclovir
- Recipients that are unable to independently understand the consent form and do not
have a legally authorized representative.
We found this trial at
1
site
Minneapolis, Minnesota 55455
Principal Investigator: Priya Verghese, MD, PhD
Phone: 612-626-4424
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