ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation

NCT ID: NCT01972035

Last Updated: 2022-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-01
• Study Completion Date: 2021-02-28

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.

Conditions

Transplantation Infection; Epstein-Barr Virus Infections; Cytomegalovirus Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Valacyclovir

Intervention Type: DRUG

Experimental Arm

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.

Group Type: ACTIVE_COMPARATOR

Valganciclovir

Intervention Type: DRUG

Standard of care

Interventions

Valacyclovir

Experimental Arm

Intervention Type: DRUG

Valganciclovir

Standard of care

Intervention Type: DRUG

Other Intervention Names

Valtrex; Valacyclovir Hydrochloride; Valacyclovir HCL; Valcyte; Valganciclovir hydrochloride

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hank Balfour, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of MN

Minneapolis, Minnesota, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25824586 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25424991 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

130162

Identifier Type: -

Identifier Source: org_study_id