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

Phase 4

• Conditions: Disorder Related to Renal Transplantation; Immunosuppression Related Infectious Disease; Virus Diseases
• Interventions: Drug: mTOR inhibitor (everolimus); Drug: cyclosporine or tacrolimus

• Registration Number: NCT01289301
• Lead Sponsor: Hannover Medical School

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.

Study Timeline

• Status Verified: 2010-10
• Study First Submitted: 2011-02-02
• Study First Submitted QC: 2011-02-02
• Last Update Submitted: 2011-02-02
• Study First Posted: 2011-02-03
• Last Update Posted: 2011-02-03
• Study Start: 2011-10
• Primary Completion: 2017-10
• Study Completion: 2018-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 124

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mTOR-receiving arm	mTOR inhibitor (everolimus)	switching from calcineurin-inhibitor-based immunosuppression to mTOR-based immunosuppression
calcineurin-inhibitor keeping arm	cyclosporine or tacrolimus	continuing calcineurin-inhibitor based immunosuppression

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)

Trial Locations

Locations (4)

University of Erlangen/ Nürnberg, Transplant Outpatient Clinic; 🇩🇪 Erlangen, Bayern, Germany

University of Essen, Transplant Outpatient Clinic; 🇩🇪 Essen, Ruhrgebiet, Germany

Hannover Medical School, Transplant Outpatient Clinic; 🇩🇪 Hannover, Niedersachsen, Germany

University Hospital Freiburg, Transplant Outpatient Clinic; 🇩🇪 Freiburg, Baden-Württemberg, Germany