The Efficacy of Everolimus With Reduced-dose Tacrolimus Versus Reduced-dose Tacrolimus in Treatment of BK Virus Infection in Kidney Transplantation Recipient

Study Overview
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Brief Summary
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BK virus infection is one of the causes of renal allograft loss in the current era. Reduction of immunsuppression is the only intervention that prooved to be effective in treating of BK virus in kidney transplant recipient. However, there are evidences from retrospective and prospective studies showed that leflunomide and mTOR inhibitor such as everolimus or sirolimus have positive outcomes in treatment of BK virus in kidney tranplant recipient. The investigators conduct the RCT to compare the efficacy of leflunomide and mTOR inhibitor everolimus, in treatment of BK virus infected patients who do not respond to immunosuppression reduction.

Official Title
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The Efficacy of Everolimus With Reduced-dose Tacrolimus Versus Reduced-dose Tacrolimus in Treatment of BK Virus Infection in Kidney Transplantation Recipient

Conditions
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BK Virus Infection, Kidney Transplant Infection

Intervention / Treatment
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* Drug: Everolimus
* Drug: reduced dose tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant recipients at King Chulalongkorn Memorial Hospital age >= 18 years persistent BK viremia >1000 copies/mL at least 2 times in 3 weeks or single time > 10000 copies/mL Exclusion Criteria: BK VL >10^5 log Previous BKVAN treatment Drug hypersensitivity to mTORi or leflunomide

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: mTORi with reduced-dose tacrolimus<br>Patient will received everolimus with target trough concentration of 3-6 ng/mL and tacrolimus with target trough concentration of 2-4 ng/mL. Duration for this regimen would be at least 3 months. | Drug: Everolimus<br>* Everolimus will be given with tacrolimus.<br>|
| Active Comparator: reduced-dose tacrolimus<br>Patient will receive tacrolimus with target concentration of 3-6 ng/mL with or without leflunomide 100 mg/day loading dose for 5 days, followed by 40 mg/day thereafter. Duration for this regimen would be at least 3 months. | Drug: reduced dose tacrolimus<br>* Reduced dose tacrolimus will be given with or without leflunomide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma BK viral load change | 3-month plasma BK viral load change from randomization | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma BK viral load clearance rate | Percentage of patients who have negative plasma BK virus at specific time point after randomization | 1, 3, 6 months | 
| Acute rejection rate |  | 6 months | 
| Glomerular filtration rate (GFR) change | GFR change at specific timepoint after randomization | 3, 6 months | 
| Chronicity score in kidney allograft | Banff's criteria for allograft biopsy tissue, focus on ci and ct scores ranging from 0 (no chronicity lesion) to 3 (severe chronicity lesion) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplantation, mTOR inhibitor, Leflunomide, BK virus