Clinical trial NCT01972035: ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
Official title: ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transplantation Infection
Epstein-Barr Virus Infections
Cytomegalovirus Infections
Keywords: EBV
CMV
Kidney transplant
valganciclovir
valacyclovir
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2013-10-30
Enrollment: 137
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Compare Incidence, Duration and Magnitude of CMV and EBV Viremia in Kidney Transplant Recipients Receiving valA vs. valG.
timeFrame: First year post-kidney transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of MN
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Hank Balfour, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kacer M, Kielberger L, Bouda M, Reischig T. Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective. Transpl Infect Dis. 2015 Jun;17(3):334-41. doi: 10.1111/tid.12383. Epub 2015 May 26.
citation: Reischig T, Kacer M, Jindra P, Hes O, Lysak D, Bouda M. Randomized trial of valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation. Clin J Am Soc Nephrol. 2015 Feb 6;10(2):294-304. doi: 10.2215/CJN.07020714. Epub 2014 Nov 25.