Is Valacyclovir Non-inferior to Valganciclovir as CMV and EBV Prophylaxis in Kidney Transplant Recipients? A Single-Center Prospective Randomized Pilot Study

Non-Inferiority Assessment of Valacyclovir Versus Valganciclovir as Prophylaxis Against CMV and EBV Viremia in Kidney Transplant Recipients: A Single-Center Prospective Randomized Pilot Study.

Opportunistic CMV viremia (primary infection or reactivation) is usually managed by taking prophylactic medication for both adult and pediatric kidney transplant patients. Most hospitals prescribe valganciclovir for this purpose but valacyclovir has also been used. The most unfavorable side effect of valganciclovir is bone marrow suppression which can be troublesome for kidney transplant patients who are already immunosuppressed. We aim to assess the non-inferiority of valacyclovir compared with valganciclovir in this study.

Study Overview

• Status: Recruiting
• Conditions: EBV Infection; Kidney Transplantation, Cytomegalovirus Infections; Antiviral Prophylaxis
• Intervention / Treatment: Drug: Valacyclovir (Valtrex); Drug: Valganciclovir (Valcyte)

Detailed Description

CMV viremia and EBV viremia are commonly seen in immunosuppressed kidney transplant recipients. These patients are at highest risk for CMV or EBV viremia early post-transplant or during a period of heightened immunosuppressive regimen to treat acute rejection. CMV viremia could be asymptomatic when the viral load is low, but if uncontrolled, it could lead to severe organ-invasive disease. On the other hand, EBV viremia, though usually not an immediate threat to allograft, harbors risk for post-transplant lymphoproliferative disease (PTLD).Therefore, most transplant centers adopt regular surveillance as well as following certain protocols of antiviral prophylaxis, using valganciclovir specifically against CMV viremia.

Valganciclovir is highly effective as prophylaxis for CMV viremia, but it is also known for its side effects such as myelosuppression and nephrotoxicity. Valacyclovir, though better known for its therapeutic effect for herpes simplex virus, is emerging as an alternative to valganciclovir since some retrospective studies showing its comparative efficacy in CMV prophylaxis. Valacyclovir has favorable side effect profile, and is less expensive. It may also reduce EBV viral shedding in oropharynx, though there's no evidence showing its efficacy in preventing EBV viremia or even PTLD in kidney transplant patients. Given that there are scarce prospective studies comparing these two medications in kidney transplant recipients, our study aims to assess the non-inferiority of valacyclovir compared with valganciclovir as prophylaxis for CMV viremia and investigate its non-inferiority for EBV viremia. We will include both pediatric and adult kidney transplant recipients who received kidney transplant less than 5 years prior to study participation and the patients will be stratified based on their age, years post-transplant, and CMV risk status. Serum viral load and other possible side effects will be monitored during their clinic visits for at least 2 years. The findings from this study will be informative for the design and power calculations for a larger multicenter non-inferiority trial. If valacyclovir is indeed non-inferior to valgancyclovir in both CMV viremia and EBV viremia, utilizing this medication in our post-kidney transplant protocol may help reduce side effect burden and potentially save substantial healthcare cost.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hou-Xuan Huang, MD; Phone Number: 270282 886-2312-3456; Email: hxhuang@ntuh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Hou-Xuan Huang, MD; Phone Number: 270282 886-2312-3456; Email: hxhuang@ntuh.gov.tw
    • Sub-Investigator: Yi-Jen Huang, PharmD
    • Principal Investigator: Hou-Xuan Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age at least 3 years of age
• Patients who are about to receive or just received kidney transplantation within the past 2 weeks before the date of screening.
• Will be receiving prophylactic antiviral therapy against CMV and/or EBV per discretion of transplant surgeon
• No active CMV or EBV viremia (as defined by detectable viral load PCR) at the time of screening.
• Ability and willingness of the patient (or parent/legal guardian for minors) to provide informed consent and comply with study procedures.

Exclusion Criteria:

• Severe co-morbidities that would preclude safe participation as judged by the transplant surgeon
• Pregnancy (valganciclovir is likely teratogenic)
• Known allergy to both valacyclovir and valganciclovir

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group (Valacyclovir); Standard adult dose for Valacyclovir will be 1000 mg orally twice daily. For pediatric patients, dosing will be weight-based 20 mg/kg/dose twice daily; maximum dose: 1000 mg/dose. The exact dosage will be adjusted for renal function based on published guidelines. Patients will continue their assigned prophylactic regimen for at least 6 months.	Drug: Valacyclovir (Valtrex); Standard adult dose will be 1000 mg orally twice daily. For pediatric patients, dosing will be weight-based 20 mg/kg/dose twice daily; maximum dose: 1000 mg/dose. The exact dosage will be adjusted for renal function based on published guidelines.
Active Comparator: Control group (Valganciclovir); Standard adult dose for Valganciclovir will be 450 mg orally once daily. For pediatric patients, dosing will be weight-based 15 mg/kg/dose once daily; maximum dose: 450 mg/dose. The exact dosage will be adjusted for renal function based on published guidelines. For pediatric patients who could not swallow pills, Valganciclovir also comes in the form of suspension (prepared by National Taiwan University Hospital in-house pharmacy). Patients will continue their assigned prophylactic regimen for at least 6 months.	Drug: Valganciclovir (Valcyte); Dosing: Standard adult dose will be 450 mg orally once daily. For pediatric patients, dosing will be weight-based 15 mg/kg/dose once daily; maximum dose: 450 mg/dose. The exact dosage will be adjusted for renal function based on published guidelines. For pediatric patients who could not swallow pills, Valcyte also comes in the form of suspension (prepared by National Taiwan University Hospital in-house pharmacy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to new-onset CMV viremia	up to 2 years
Time to new-onset EBV viremia	up to 2 years
Cumulative incidence of new-onset CMV viremia	6 months, 1year, and 2 years
Cumulative incidence of new-onset EBV viremia	6 months, 1 year, and 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Marrow Suppression	The cumulative incidence of specific cytopenia (leukopenia, neutropenia, thrombocytopenia and anemia respectively) in each treatment arm will be compared.	6 months, 1 year, 2 years
Significantly declined renal function at 2 years post-transplant	The incidence of significant decline in renal function (e.g., >20% decrease from baseline or progression to CKD stage 5) will be compared between groups	2 years
Other adverse events during study period	The incidence of other adverse events will be tabulated and compared between groups	2 years
Magnitude of Viral Load in New-Onset CMV Viremia	For patients who develop new-onset CMV viremia, the peak CMV viral load (IU/mL) during the viremic episode will be identified.	2 years
Magnitude of Viral Load in New-Onset EBV Viremia	For patients who develop new-onset EBV viremia, the peak EBV viral load (IU/mL) during the viremic episode will be identified.	2 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Publications and helpful links

General Publications

• 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.
• Kim JS, Lee NR, Park KI, Hwang HS, Lee SH, Chung BH, Jung CW, Cho JH, Park WY, Kim HJ, Jeong JC, Yang J, Lee YH, Park JB, Jeon JS, Lee J, Kim YH, Choi SJN, Oh J, Yoon HE, Kim DG, Shin HS, Ban TH, Kim MS, Ko MJ, Jeong KH; KOTRY study group. Valacyclovir for the prevention of cytomegalovirus infection after kidney transplantation. BMC Infect Dis. 2025 Mar 5;25(1):314. doi: 10.1186/s12879-025-10671-6.
• Hoshino Y, Katano H, Zou P, Hohman P, Marques A, Tyring SK, Follmann D, Cohen JI. Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers. J Virol. 2009 Nov;83(22):11857-61. doi: 10.1128/JVI.01005-09. Epub 2009 Sep 9.
• Cardoso LJC, Martins KAM, Marques PV, Teixeira IPS, Magalhaes E, Minkauskas JL, Faria IC, Ribeiro FM. Valacyclovir versus valganciclovir for cytomegalovirus prophylaxis in kidney transplant recipients: a systematic review and comparative meta-analysis. Clin Transplant Res. 2025 Mar 31;39(1):24-35. doi: 10.4285/ctr.24.0034. Epub 2024 Nov 8.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Non-Inferiority Assessment of Valacyclovir versus Valganciclovir as Prophylaxis Against CMV and EBV Viremia in Kidney Transplant Recipients
• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Epstein-Barr Virus Infections; Cytomegalovirus Infections; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Guanine; Hypoxanthines; Purinones; Purines; Ganciclovir; Acyclovir; Valacyclovir; Valganciclovir
• Other Study ID Numbers: 202507077MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No