Impact of Immunosuppressive Regimens on Polyomavirus-related Transplant Nephropathy

University of Giessen

Status and phase: Completed; Phase 4

Conditions: Polyomavirus Infections

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00160966

NTx-PV-002

Details and patient eligibility

About

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

Full 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).

Enrollment: 108 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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108 participants in 3 patient groups

1

Active Comparator group

Description:

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.

Treatment:

Drug: Ciclosporin and Mycophenolate-mofetil

2

Active Comparator group

Description:

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.

Treatment:

Drug: Tacrolimus and Mycophenolate-mofetil

3

Active Comparator group

Description:

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

Treatment:

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