Studying the Effect of Changing Immunosuppression in Case of Polyoma BK Virus Infection of the Renal Transplant

Study Overview
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Brief Summary
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Polyomavirus BK nephropathy is a serious complication after renal transplantation leading to graft loss in 40% of cases. Since no virustatic drug exists, the investigators want to study the best way to manage viral invasion by changing the immunosuppressive treatment comparing two treatment schemes. The investigators hypothesis is that switching to an mTOR-based scheme is superior to a general decrease of a calcineurin inhibitor (CNI)-based scheme. The study will be performed as a prospective, randomized, parallel group comparison.

Detailed Description
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The study group (n=62) will be switched from CNI to everolimus while the control group (n=62) will get a general reduction of the CNI-based immunosuppression. Follow-up and duration of intervention per patient will be 24 months, duration of the trial 72 months including 4 years of recruitment.

Official Title
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Polyomavirus BK Nephropathy After Renal Transplantation: Randomized Clinical Trial to Demonstrate That Switching to mTOR Inhibitor is More Effective Than a Reduction of Immunosuppressive Therapy

Conditions
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Disorder Related to Renal Transplantation, Immunosuppression Related Infectious Disease, Virus Diseases

Intervention / Treatment
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* Drug: mTOR inhibitor (everolimus)
* Drug: cyclosporine or tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: preceding renal transplantation functioning graft with a permanent creatinine clearance of more than 25mL/min biopsy-confirmed polyoma BK virus nephropathy age over 18 years old Exclusion Criteria: allergy or non-tolerance of the study medication everolimus pregnancy

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 |
| --- | --- |
| Experimental: mTOR-receiving arm<br>switching from calcineurin-inhibitor-based immunosuppression to mTOR-based immunosuppression | Drug: mTOR inhibitor (everolimus)<br>* calcineurin-inhibitor based immunosuppression will be switched to immunosuppression based on m-TOR inhibitor (everolimus trough level 3-7ng/mL)<br>* Other names: switch immunosuppression to everolimus;|
| Active Comparator: calcineurin-inhibitor keeping arm<br>continuing calcineurin-inhibitor based immunosuppression | Drug: cyclosporine or tacrolimus<br>* calcineurin inhibitor (cyclosporine or tacrolimus) will be continued (trough level 60-90ng/mL resp 3-7ng/mL)<br>* Other names: tacrolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death or graft loss | after experimental intervention (switch to mTOR inhibitor in group 1) and control intervention (general reduction of immunosuppression) observation of graft function | 2 years of observation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| decrease of polyomavirus serum PCR | regular measurement of polyomavirus serum PCR (every 4 weeks to 3 months) | 2 years | 
| decrease of creatinine | regular measurment of graft function (every 4 weeks to 3 months) | 2 years observation | 
| progression of chronic changes in renal histology | renal rebiopsy and comparison of chronic changes in renal biopsy with the diagnostic renal biopsy | renal biopsy 3 months after intervention | 
| number of rejections following intervention | biopsy-verified rejections (graft biopsies on indication) may be a consequence of changement of immunosuppression and a side effect of it, rejections will be counted | 2 years after intervention | 
| increase of BKV-specific T-cells | increase of BKV-specific T-cells are a sign of overcoming viral infection and will be counted regularly (every 3 to 6 months) | 2 years observation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal transplantation, polyoma BK virus infection, everolimus, calcineurin inhibitor, mTOR inhibitor