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ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation

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: NCT01972035
Recruitment Status : Completed
First Posted : October 30, 2013
Results First Posted : March 16, 2022
Last Update Posted : April 12, 2022
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

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.


Condition or disease Intervention/treatment Phase
Transplantation Infection Epstein-Barr Virus Infections Cytomegalovirus Infections Drug: Valacyclovir Drug: Valganciclovir Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 137 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
Actual Study Start Date : August 1, 2014
Actual Primary Completion Date : February 28, 2021
Actual Study Completion Date : February 28, 2021


Arm Intervention/treatment
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 3-12 months depending on risk and age of recipient. 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 3-12 months depending on risk and age of recipient. Dosing is based on glomerular filtration rate.
Drug: Valganciclovir
Standard of care
Other Names:
  • Valcyte
  • Valganciclovir hydrochloride




Primary Outcome Measures :
  1. Compare Incidence, Duration and Magnitude of CMV and EBV Viremia in Kidney Transplant Recipients Receiving valA vs. valG. [ Time Frame: First year post-kidney transplant ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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): NCT01972035


Locations
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United States, Minnesota
University of MN
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota
Investigators
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Principal Investigator: Hank Balfour, MD University of Minnesota
  Study Documents (Full-Text)

Documents provided by University of Minnesota:
Informed Consent Form  [PDF] July 11, 2018

Publications:
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT01972035    
Other Study ID Numbers: 130162
First Posted: October 30, 2013    Key Record Dates
Results First Posted: March 16, 2022
Last Update Posted: April 12, 2022
Last Verified: March 2022
Keywords provided by University of Minnesota:
EBV
CMV
Kidney transplant
valganciclovir
valacyclovir
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Cytomegalovirus Infections
Epstein-Barr Virus Infections
Disease Attributes
Pathologic Processes
Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Valacyclovir
Valganciclovir
Antiviral Agents
Anti-Infective Agents