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Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy

This study has been completed.
Sponsor:
Collaborators:
Heidelberg University
Hoffmann-La Roche
Astellas Pharma Inc
Novartis
Information provided by (Responsible Party):
Prof. Dr. Rolf Weimer, University of Giessen
ClinicalTrials.gov Identifier:
NCT00160966
First received: September 8, 2005
Last updated: March 27, 2017
Last verified: January 2017
  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: Ciclosporin and Mycophenolate-mofetil
Drug: Tacrolimus and Mycophenolate-mofetil
Drug: Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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:


Further study details as provided by University of Giessen:

Primary Outcome Measures:
  • incidence of polyomavirus associated transplant nephropathy (PVN) [ Time Frame: 2 years posttransplant ]
  • incidence of polyoma viremia [ Time Frame: 2 years posttransplant ]
  • urine polyomavirus concentration within the first two years post-transplant [ Time Frame: 2 years posttransplant ]

Secondary Outcome Measures:
  • patients' and grafts' survival [ Time Frame: 2 years posttransplant ]
  • incidence of acute rejections [ Time Frame: 2 years posttransplant ]
  • transplant function 1 and 2 years post-transplant [ Time Frame: 2 years posttransplant ]
  • comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN [ Time Frame: 2 years posttransplant ]
  • predictive value of immune parameters prognostically relevant for acute or chronic rejection [ Time Frame: 2 years posttransplant ]
  • side effects of immunosuppressive drugs [ Time Frame: 2 years posttransplant ]

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 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
according to the Giessen protocol
Active Comparator: 2
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
according to Giessen protocol
Active Comparator: 3
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
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   (Adult, Senior)
Sexes Eligible for Study:   All
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
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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
Heidelberg University
Hoffmann-La Roche
Astellas Pharma Inc
Novartis
Investigators
Principal Investigator: Rolf Weimer, Prof., MD University Giessen, Internal Medicine
  More Information

Publications:

Responsible Party: Prof. Dr. Rolf Weimer, Prof. Dr., 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: March 27, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: De-identified data of all participants will be made available within 1 year of study completion.

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
Everolimus
Sirolimus
Mycophenolic Acid
Tacrolimus
Mycophenolate mofetil
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 27, 2017