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

Sponsor

Hannover Medical School (Other)

Overall Status

Unknown status

CT.gov ID

NCT01289301

Collaborator

(none)

124

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Disorder Related to Renal Transplantation Immunosuppression Related Infectious Disease Virus Diseases	Drug: mTOR inhibitor (everolimus) Drug: cyclosporine or tacrolimus	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2011

Anticipated Primary Completion Date :

Oct 1, 2017

Anticipated Study Completion Date :

Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mTOR-receiving arm switching from calcineurin-inhibitor-based immunosuppression to mTOR-based immunosuppression	Drug: mTOR inhibitor (everolimus) calcineurin-inhibitor based immunosuppression will be switched to immunosuppression based on m-TOR inhibitor (everolimus trough level 3-7ng/mL) Other Names: switch immunosuppression to everolimus
Active Comparator: calcineurin-inhibitor keeping arm continuing calcineurin-inhibitor based immunosuppression	Drug: cyclosporine or tacrolimus calcineurin inhibitor (cyclosporine or tacrolimus) will be continued (trough level 60-90ng/mL resp 3-7ng/mL) Other Names: keeping immunosuppression with calcineurin inhibitor cyclosporine tacrolimus

Arm

Intervention/Treatment

Experimental: mTOR-receiving arm

switching from calcineurin-inhibitor-based immunosuppression to mTOR-based immunosuppression

Drug: mTOR inhibitor (everolimus)

calcineurin-inhibitor based immunosuppression will be switched to immunosuppression based on m-TOR inhibitor (everolimus trough level 3-7ng/mL)

Other Names:

switch immunosuppression to everolimus

Active Comparator: calcineurin-inhibitor keeping arm

continuing calcineurin-inhibitor based immunosuppression

Drug: cyclosporine or tacrolimus

calcineurin inhibitor (cyclosporine or tacrolimus) will be continued (trough level 60-90ng/mL resp 3-7ng/mL)

Other Names:

keeping immunosuppression with calcineurin inhibitor

cyclosporine

tacrolimus

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Freiburg, Transplant Outpatient Clinic	Freiburg	Baden-Württemberg	Germany	D-79104
2	University of Erlangen/ Nürnberg, Transplant Outpatient Clinic	Erlangen	Bayern	Germany	D-91054
3	Hannover Medical School, Transplant Outpatient Clinic	Hannover	Niedersachsen	Germany	D-30625
4	University of Essen, Transplant Outpatient Clinic	Essen	Ruhrgebiet	Germany	D-45122

Sponsors and Collaborators

Hannover Medical School

Investigators

Principal Investigator: Anke Schwarz, Prof. Dr., Hannover Medical School, Nephrology
Principal Investigator: Hermann Haller, Prof. Dr., Hannover Medical School, Nephrology
Study Chair: Silvia Linnenweber, Dr., Hannover Medical School, Nephrology
Study Director: Armin Koch, Prof. Dr., Hannover Medical School, Biometry
Study Director: Albert Heim, PD Dr., Hannover Medical School, Virology
Study Chair: Verena Broecker, Dr., Hannover Medical School, Pathology