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

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

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.

Study Overview

• Status: Unknown
• Conditions: Virus Diseases; Disorder Related to Renal Transplantation; Immunosuppression Related Infectious Disease
• Intervention / Treatment: Drug: mTOR inhibitor (everolimus); Drug: cyclosporine or tacrolimus

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 Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anke Schwarz, Prof. Dr.; Phone Number: +49 511 532 2329; Email: schwarz.anke@mh-hannover.de
• Study Contact Backup: Name: Hermann Haller, Prof. Dr.; Phone Number: +49 511 5326319; Email: haller.hermann@mh-hannover.de

Study Locations

• Germany
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, D-79104
      • University Hospital Freiburg, Transplant Outpatient Clinic
      • Contact: Gerd Walz, Prof. Dr.; Phone Number: 0761 2703250; Email: gerd.walz@uniklinik-freiburg.de
  • Bayern
    • Erlangen, Bayern, Germany, D-91054
      • University of Erlangen/ Nürnberg, Transplant Outpatient Clinic
      • Contact: Karl Hilgers, Prof. Dr.; Phone Number: +49 9131 8536267; Email: karl.hilgers@uk-erlangen.de
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, D-30625
      • Hannover Medical School, Transplant Outpatient Clinic
      • Contact: Anke Schwarz, Prof. Dr.; Phone Number: +49 511 5322329; Email: schwarz.anke@mh-hannover.de
      • Contact: Silvia Linnenweber, Dr.; Phone Number: +49 511 5323000; Email: linnenweber.silvia@mh-hannover.de
  • Ruhrgebiet
    • Essen, Ruhrgebiet, Germany, D-45122
      • University of Essen, Transplant Outpatient Clinic
      • Contact: Oliver Witzke, Prof. Dr.; Phone Number: +49 201 7231868; Email: nephrologie@uk-essen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: tacrolimus; cyclosporine; keeping immunosuppression with calcineurin inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: February 2, 2011
• First Submitted That Met QC Criteria: February 2, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Estimate): February 3, 2011
• Last Update Submitted That Met QC Criteria: February 2, 2011
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: everolimus; mTOR inhibitor; renal transplantation; calcineurin inhibitor; polyoma BK virus infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Virus Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Tacrolimus; Everolimus; Sirolimus; Cyclosporine; Cyclosporins; Calcineurin Inhibitors
• Other Study ID Numbers: Polyoma IFB 29