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Open Access Research article

A multicenter, randomized, double-blind study comparing different FK778 doses (manitimus) with tacrolimus and steroids vs. MMF with tacrolimus and steroids in renal transplantation

Zbigniew Wlodarczyk1*, Yves Vanrenterghem2, Bernhard K Krämer3, Jean-Paul Squifflet4 and Marek Ostrowski5

Author Affiliations

1 Klinika Transplantologii, Szpital Uniwersytecki, Bydgoszcz, Poland

2 Inwendige Geneeskunde-Nefrologie-Nierentransplantatie, Universitaire Ziekenhuizen Gasthuisberg, Leuven, Belgium

3 V Medizinische Klinik, Universitätsklinikum Mannheim, University of Heidelberg, Mannheim, Germany

4 Chirurgie Abdominale, Senologique, Endocrine et de Transplantation, Centre Hospitalier Universitaire, Liege, Belgium

5 Klinika Chirurgii Ogólnej I Transplantacyjnej S.P.S.K. 2, Szczecin, Poland

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BMC Nephrology 2012, 13:68  doi:10.1186/1471-2369-13-68

Published: 26 July 2012

Abstract

Background

This multicenter phase II study in renal transplantation compared 3 concentration-controlled ranges of FK778 (manitimus) with mycophenolate mofetil (MMF) both given in combination with tacrolimus and corticosteroids.

Methods

364 patients were randomized to 12-month treatment: high-level FK778 group (H, N = 87) received 4x600mg/day (4 days) followed by 120 mg/day; mid-level FK778 group (M, N = 92) received 3x600mg/day (3 days) followed by 110 mg/day, low-level FK778 group (L, N = 92) received 2x600mg/day (2 days) followed by 100 mg/day, and control group received MMF 1 g/day (MMF, N = 93). After week 6, FK778 doses were adjusted to trough ranges of 75–125 μg/mL (H), 50–100 μg/mL (M) and 25–75 μg/mL (L). Tacrolimus and steroids were administered at the same dose in each of the 4 groups.

Results

Biopsy proven acute rejection (BPAR) at 24 weeks, the primary study endpoint, was comparable in the L (22.8%) and MMF (17.2%) groups but higher in the H (34.5%) and M (29.3%) groups. BPAR at 12 months was comparable in the L (23.9%) and MMF (19.4%) groups but higher in the H (34.5%) and M (31.5%) groups. Graft and patient survival were lowest in the H group and renal function was poorest in the H and M groups. Premature study withdrawal was highest in the H group.

Conclusions

Efficacy was similar between the low-level FK778 and MMF groups. Increased FK778 exposure was poorly tolerated and did not improve efficacy.