Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy - Full Text View

Purpose

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

Condition	Intervention	Phase
Polyomavirus Infections	Drug: CsA + MMF Drug: Tacr + MMF Drug: Tacr + MMF with conversion to Tacr + ERL	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Prospective Randomized Study to Characterize Risk Factors of Polyomavirus-related Transplant Nephropathy and the Impact of Three Immunosuppressive Regimens on Nephropathy Incidence

Resource links provided by NLM:

MedlinePlus related topics: Urine and Urination

U.S. FDA Resources

Further study details as provided by University of Giessen:

Primary Outcome Measures:

incidence of polyomavirus associated transplant nephropathy (PVN) [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: Yes ]
incidence of polyoma viremia [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: Yes ]
urine polyomavirus concentration within the first two years post-transplant [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

patients' and grafts' survival [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: Yes ]
incidence of acute rejections [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: Yes ]
transplant function 1 and 2 years post-transplant [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: No ]
comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: No ]
predictive value of immune parameters prognostically relevant for acute or chronic rejection [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: No ]
side effects of immunosuppressive drugs [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: Yes ]

Enrollment:	108
Study Start Date:	September 2004
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Immunosuppression with CsA/MMF	Drug: CsA + MMF according to the Giessen protocol
Active Comparator: 2 Immunosuppression with Tacr/MMF	Drug: Tacr + MMF according to Giessen protocol
Active Comparator: 3 Immunosuppression with Tacr/MMF with change from MMF to Everolimus after completion of posttransplant wound healing	Drug: Tacr + MMF with conversion to Tacr + ERL according to Giessen protocol

Detailed Description:

Polyomavirus nephropathy (PVN) is an emerging cause of renal transplant loss. Until now the risk factors of PVN are poorly understood. Tacrolimus (Tacr) and mycophenolate mofetil (MMF) are thought to be associated with a higher risk of developing PVN. However, the way in which Tacr or MMF might enhance the susceptibility for PVN remains largely unknown. In this prospective study we will analyze whether differences in immune-reactivity patterns (Th1, Th2, B cell and monocyte responses, sCD30, immunoregulatory antibodies) of renal transplant patients induced by different immunosuppressive regimens (cyclosporine A [CsA]/MMF, Tacr/MMF, Tacr/MMF with conversion to Tacr/Everolimus [ERL]) or by cytokine promoter gene polymorphisms may account for the different risks of developing PVN.

Comparison(s): renal transplant recipients stratified according to their relative immunological risk (group 1: low risk (primary recipients without pre-immunization [PRA < 5%]); group 2: moderate risk (group 2a: primary recipients with low pre-immunization [PRA 6-20%]; group 2b: re-transplanted patients); group 3: very high risk (re-transplanted patients with a history of vascular rejection or recipients of a first graft with high pre-immunization [PRA > 20%]) randomized to be treated with one of three immunosuppressive regimens (CsA/MMF, Tacr/MMF, Tacr/MMF with subsequent conversion to Tacr/ERL).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00160966

Locations

Germany
Department of Internal Medicine, University of Giessen
Giessen, Germany, 35392

Sponsors and Collaborators

University of Giessen

University of Heidelberg

Hoffmann-La Roche

Astellas Pharma Inc

Novartis

Investigators

Principal Investigator:

Rolf Weimer, Prof., MD

University Giessen, Internal Medicine

More Information

Publications:

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.

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.

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. Review.

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.

Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002 Jan;2(1):25-30. Review.

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. No abstract available.

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.

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.

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.

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.

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. No abstract available.

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.

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. No abstract available.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Responsible Party:	Prof. Dr. Rolf Weimer, University of Giessen
ClinicalTrials.gov Identifier:	NCT00160966 History of Changes
Other Study ID Numbers:	NTx-PV-002
Study First Received:	September 8, 2005
Last Updated:	July 2, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Giessen:

kidney transplantation
polyoma virus associated transplant nephropathy
tacrolimus
mycophenolate mofetil
everolimus

cyclosporin A
BK virus PCR
viruria screening
BK polyomavirus
immunosuppression

Additional relevant MeSH terms:

Kidney Diseases
Polyomavirus Infections
Urologic Diseases
DNA Virus Infections
Virus Diseases

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013