Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy

NCT00160966 | Completed Phase 4 DMC

• 1 other identifier: NTx-PV-002
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to characterize and evaluate risk factors of polyomavirus nephropathy (PVN) including the impact of three immunosuppressive regimens.

Conditions

Polyomavirus Infections

Keywords

kidney transplantation; polyoma virus associated transplant nephropathy; tacrolimus; mycophenolate mofetil; everolimus; cyclosporin A; BK virus PCR; viruria screening; BK polyomavirus; immunosuppression

Outcome Measures

Primary Outcomes (3)

• incidence of polyomavirus associated transplant nephropathy (PVN)

  2 years posttransplant

• incidence of polyoma viremia

  2 years posttransplant

• urine polyomavirus concentration within the first two years post-transplant

  2 years posttransplant

Secondary Outcomes (6)

• patients' and grafts' survival

  2 years posttransplant

• incidence of acute rejections

  2 years posttransplant

• transplant function 1 and 2 years post-transplant

  2 years posttransplant

• comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN

  2 years posttransplant

• predictive value of immune parameters prognostically relevant for acute or chronic rejection

  2 years posttransplant

Study Arms (3)

1

ACTIVE COMPARATOR

Immunosuppression with Ciclosporin and Mycophenolate-mofetil; Ciclosporin treatment being started at the latest at day 4 after transplantation with 7 mg/kg body weight daily administered every 8 hours until the target trough level of 300 µg/l was reached. Then it was administered twice daily with daily monitoring of trough levels. The target trough level was lowered to 200 µg/l 1 month after transplantation. Thereafter dosage and target trough levels were adjusted at the investigators discretion. Mycophenolate-mofetil was started previous to transplantation procedure with a starting dosage of 3 g/day administered twice daily. Once ciclosporin was entered into the therapy-scheme Mycophenolate-mofetil dosage was reduced to 2 g/daily. The therapy was controlled by measuring of trough levels with a target trough level exceeding 1 µg/ml. The dosage was adjusted at the investigators discretion.

Drug: Ciclosporin and Mycophenolate-mofetil

2

ACTIVE COMPARATOR

Immunosuppression with Tacrolimus and Mycophenolate-mofetil Mycophenolate-mofetil was started previous to transplantation procedure with a starting dosage of 3 g/day administered twice daily. Once tacrolimus was entered into the therapy-scheme Mycophenolate-mofetil dosage was reduced to 2 g/daily. The therapy was controlled by measuring of trough levels with a target trough level exceeding 1 µg/ml. The dosage was adjusted to clinical signs of overimmunosuppression (infections) or intolerance (mainly gastrointestinal side effects) or rejections.

Drug: Tacrolimus and Mycophenolate-mofetil

3

ACTIVE COMPARATOR

Immunosuppression with Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus after completion of posttransplant wound healing

Drug: Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus

Interventions

Ciclosporin and Mycophenolate-mofetil DRUG

according to the Giessen protocol

1

Tacrolimus and Mycophenolate-mofetil DRUG

according to Giessen protocol

2

Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus DRUG

according to Giessen protocol

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cadaver kidney and living donor kidney transplant recipients
• Primary, secondary, and tertiary transplant recipients
• Pre-immunized and not pre-immunized transplant recipients
• Age \> 18 years

You may not qualify if:

• Contraindications against administration of one of the four study drugs
• History of severe gastrointestinal morbidity
• Age \< 18 years
• Pregnant or breast feeding women
• Rejection of effective contraceptive methods with young women
• Combined kidney and islet cell transplantation

Sponsors & Collaborators

• University of Giessen: lead
• Heidelberg University: collaborator
• Hoffmann-La Roche: collaborator
• Astellas Pharma Inc: collaborator
• Novartis: collaborator

Study Sites (1)

Department of Internal Medicine, University of Giessen

Giessen, 35392, Germany

Location

Related Publications (23)

• Andrews CA, Shah KV, Daniel RW, Hirsch MS, Rubin RH. A serological investigation of BK virus and JC virus infections in recipients of renal allografts. J Infect Dis. 1988 Jul;158(1):176-81. doi: 10.1093/infdis/158.1.176.

  PMID: 2839580 BACKGROUND

• Barri YM, Ahmad I, Ketel BL, Barone GW, Walker PD, Bonsib SM, Abul-Ezz SR. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant. 2001 Aug;15(4):240-6. doi: 10.1034/j.1399-0012.2001.150404.x.

  PMID: 11683817 BACKGROUND

• Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, Mihatsch MJ. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant. 2000 Mar;15(3):324-32. doi: 10.1093/ndt/15.3.324.

  PMID: 10692517 BACKGROUND

• Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002 Aug 15;347(7):488-96. doi: 10.1056/NEJMoa020439.

  PMID: 12181403 BACKGROUND

• Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002 Jan;2(1):25-30. doi: 10.1034/j.1600-6143.2002.020106.x.

  PMID: 12095052 BACKGROUND

• Hirsch HH, Mohaupt M, Klimkait T. Prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. J Infect Dis. 2001 Dec 1;184(11):1494-5; author reply 1495-6. doi: 10.1086/324425. No abstract available.

  PMID: 11709797 BACKGROUND

• Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, Mihatsch MJ, Thiel G. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation. 1999 Mar 27;67(6):918-22. doi: 10.1097/00007890-199903270-00022.

  PMID: 10199744 BACKGROUND

• Weimer R, Susal C, Yildiz S, Streller S, Pelzl S, Staak A, Renner F, Dietrich H, Daniel V, Feuring E, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil. Transplant Proc. 2005 May;37(4):1776-8. doi: 10.1016/j.transproceed.2005.02.088.

  PMID: 15919463 BACKGROUND

• Weimer R, Staak A, Susal C, Streller S, Yildiz S, Pelzl S, Renner F, Dietrich H, Daniel V, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. ATG induction therapy: long-term effects on Th1 but not on Th2 responses. Transpl Int. 2005 Feb;18(2):226-36. doi: 10.1111/j.1432-2277.2004.00047.x.

  PMID: 15691277 BACKGROUND

• Weimer R, Mytilineos J, Feustel A, Preiss A, Daniel V, Grimm H, Wiesel M, Opelz G. Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients. Transplantation. 2003 Jun 27;75(12):2090-9. doi: 10.1097/01.TP.0000058808.37349.23.

  PMID: 12829918 BACKGROUND

• Weimer R, Streller S, Staak A, Heilke M, Li D, Dietrich H, Daniel V, Feustel A, Rainer L, Zinn S, Friemann S, Ernst W, Grimm H, Padberg W, Zimmermann T, Opelz G. Effects of three immunosuppressive regimens on CD4 helper function, B cell monocyte and cytokine responses in renal transplant recipients: 4-month follow-up of a prospective randomized study. Transplant Proc. 2002 Sep;34(6):2377-8. doi: 10.1016/s0041-1345(02)03278-5. No abstract available.

  PMID: 12270445 BACKGROUND

• Weimer R, Melk A, Daniel V, Friemann S, Padberg W, Opelz G. Switch from cyclosporine A to tacrolimus in renal transplant recipients: impact on Th1, Th2, and monokine responses. Hum Immunol. 2000 Sep;61(9):884-97. doi: 10.1016/s0198-8859(00)00152-x.

  PMID: 11053632 BACKGROUND

• Daniel V, Arzberger J, Melk A, Weimer R, Ruhenstroth A, Carl S, Wiesel M, Opelz G. Predictive indicators of rejection or infection in renal transplant patients. Transplant Proc. 1999 Feb-Mar;31(1-2):1364-5. doi: 10.1016/s0041-1345(98)02030-2. No abstract available.

  PMID: 10083605 BACKGROUND

• Weimer R, Zipperle S, Daniel V, Carl S, Staehler G, Opelz G. Pretransplant CD4 helper function and interleukin 10 response predict risk of acute kidney graft rejection. Transplantation. 1996 Dec 15;62(11):1606-14. doi: 10.1097/00007890-199612150-00014.

  PMID: 8970616 BACKGROUND

• Daniel V, Pasker S, Wiesel M, Carl S, Pomer S, Staehler G, Schnobel R, Weimer R, Opelz G. Cytokine monitoring of infection and rejection in renal transplant recipients. Transplant Proc. 1995 Feb;27(1):884-6. No abstract available.

  PMID: 7879219 BACKGROUND

• Weimer R, Zipperle S, Daniel V, Pomer S, Staehler G, Opelz G. IL-6 independent monocyte/B cell defect in renal transplant recipients with long-term stable graft function. Transplantation. 1994 Jan;57(1):54-9. doi: 10.1097/00007890-199401000-00011.

  PMID: 7507271 BACKGROUND

• Weimer R, Daniel V, Zimmermann R, Schimpf K, Opelz G. Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients. Blood. 1991 Jan 1;77(1):133-40.

  PMID: 1824617 BACKGROUND

• Weimer R, Daniel V, Pomer S, Opelz G. B lymphocyte response as an indicator of acute renal transplant rejection. II. Pretransplant and posttransplant B cell responses of m mitogen and donor cell-stimulated cultures. Transplantation. 1989 Oct;48(4):572-5.

  PMID: 2678634 BACKGROUND

• Weimer R, Daniel V, Pomer S, Opelz G. B lymphocyte response as an indicator of acute renal transplant rejection. I. Immunoglobulin-secreting cells in peripheral blood. Transplantation. 1989 Oct;48(4):569-72.

  PMID: 2572082 BACKGROUND

• Susal C, Dohler B, Opelz G. Graft-protective role of high pretransplantation IgA-anti-Fab autoantibodies: confirmatory evidence obtained in more than 4000 kidney transplants. The Collaborative Transplant Study. Transplantation. 2000 Apr 15;69(7):1337-40. doi: 10.1097/00007890-200004150-00021.

  PMID: 10798750 BACKGROUND

• Pelzl S, Opelz G, Daniel V, Wiesel M, Susal C. Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection. Transplantation. 2003 Feb 15;75(3):421-3. doi: 10.1097/01.TP.0000044702.18327.66.

  PMID: 12589170 BACKGROUND

• Susal C, Pelzl S, Dohler B, Opelz G. Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30. J Am Soc Nephrol. 2002 Jun;13(6):1650-6. doi: 10.1097/01.asn.0000014256.75920.5b.

  PMID: 12039995 BACKGROUND

• Susal C, Opelz G. Kidney graft failure and presensitization against HLA class I and class II antigens. Transplantation. 2002 Apr 27;73(8):1269-73. doi: 10.1097/00007890-200204270-00014.

  PMID: 11981420 BACKGROUND

MeSH Terms

Conditions

Polyomavirus Infections

Interventions

Cyclosporine; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Rolf Weimer, Prof., MD

  University Giessen, Internal Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: September 1, 2004
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: March 28, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)