Antiviral Prophylaxis, EBV Infection, Kidney Transplantation, Cytomegalovirus Infections
Conditions
Keywords
Non-Inferiority Assessment of Valacyclovir versus Valganciclovir as Prophylaxis Against CMV and EBV Viremia in Kidney Transplant Recipients
Brief summary
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.
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.
Interventions
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.
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).
Sponsors
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Bone Marrow Suppression | 6 months, 1 year, 2 years | The cumulative incidence of specific cytopenia (leukopenia, neutropenia, thrombocytopenia and anemia respectively) in each treatment arm will be compared. |
| Magnitude of Viral Load in New-Onset EBV Viremia | 2 years | For patients who develop new-onset EBV viremia, the peak EBV viral load (IU/mL) during the viremic episode will be identified. |
| Significantly declined renal function at 2 years post-transplant | 2 years | 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 |
| Other adverse events during study period | 2 years | The incidence of other adverse events will be tabulated and compared between groups |
| Magnitude of Viral Load in New-Onset CMV Viremia | 2 years | For patients who develop new-onset CMV viremia, the peak CMV viral load (IU/mL) during the viremic episode will be identified. |
Countries
Taiwan
Contacts
Primary ContactHou-Xuan Huang, MD
Outcome results
None listed