Clinical trial NCT00160966: Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy
Official title: Prospective Randomized Study to Characterize Risk Factors of Polyomavirus-related Transplant Nephropathy and the Impact of Three Immunosuppressive Regimens on Nephropathy Incidence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
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
Lead sponsor: University of Giessen
Sponsor class: OTHER
Collaborators: name: Heidelberg University
name: Hoffmann-La Roche
name: Astellas Pharma Inc
name: Novartis
First posted: 2005-09-12
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: incidence of polyomavirus associated transplant nephropathy (PVN)
timeFrame: 2 years posttransplant
measure: incidence of polyoma viremia
timeFrame: 2 years posttransplant
measure: urine polyomavirus concentration within the first two years post-transplant
timeFrame: 2 years posttransplant
Secondary outcomes:
measure: patients' and grafts' survival
timeFrame: 2 years posttransplant
measure: incidence of acute rejections
timeFrame: 2 years posttransplant
measure: transplant function 1 and 2 years post-transplant
timeFrame: 2 years posttransplant
measure: comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN
timeFrame: 2 years posttransplant
measure: predictive value of immune parameters prognostically relevant for acute or chronic rejection
timeFrame: 2 years posttransplant
measure: side effects of immunosuppressive drugs
timeFrame: 2 years posttransplant
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: Department of Internal Medicine, University of Giessen
Study officials:
affiliation: University Giessen, Internal Medicine
name: Rolf Weimer, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
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