Disorder Related to Renal Transplantation, Immunosuppression Related Infectious Disease, Virus Diseases
Conditions
Keywords
renal transplantation, polyoma BK virus infection, everolimus, calcineurin inhibitor, mTOR inhibitor
Brief summary
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
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.
Interventions
DRUGmTOR inhibitor (everolimus)
calcineurin-inhibitor based immunosuppression will be switched to immunosuppression based on m-TOR inhibitor (everolimus trough level 3-7ng/mL)
calcineurin inhibitor (cyclosporine or tacrolimus) will be continued (trough level 60-90ng/mL resp 3-7ng/mL)
Sponsors
Hannover Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| death or graft loss | 2 years of observation | after experimental intervention (switch to mTOR inhibitor in group 1) and control intervention (general reduction of immunosuppression) observation of graft function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| decrease of polyomavirus serum PCR | 2 years | regular measurement of polyomavirus serum PCR (every 4 weeks to 3 months) |
| decrease of creatinine | 2 years observation | regular measurment of graft function (every 4 weeks to 3 months) |
| progression of chronic changes in renal histology | renal biopsy 3 months after intervention | renal rebiopsy and comparison of chronic changes in renal biopsy with the diagnostic renal biopsy |
| number of rejections following intervention | 2 years after 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 |
| increase of BKV-specific T-cells | 2 years observation | increase of BKV-specific T-cells are a sign of overcoming viral infection and will be counted regularly (every 3 to 6 months) |
Countries
Germany
Contacts
Primary ContactAnke Schwarz, Prof. Dr.
Backup ContactHermann Haller, Prof. Dr.
Outcome results
None listed