Everolimus plus early tacrolimus minimization: a phase III, randomized, open‐label, multicentre trial in renal transplantation

Authors: Langer, Robert M1; Hené, Ronald2; Vitko, Stefan3; Christiaans, Maarten4; Tedesco‐Silva, Helio5; Ciechanowski, Kazimierz6; Cassuto, Elisabeth7; Rostaing, Lionel8; Vilatoba, Mario9; Machein, Uwe10; Ulbricht, Bettina10; Junge, Guido10; Dong, Gaohong11; Pascual, Julio12

Source: Transplant International, Volume 25, Number 5, 1 May 2012 , pp. 592-602(11)

Publisher: Wiley-Blackwell

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Abstract:

Summary

There is increasing interest in tacrolimus‐minimization regimens. ASSET was an open‐label, randomized, 12‐month study of everolimus plus tacrolimus in de‐novo renal‐transplant recipients. Everolimus trough targets were 3–8 ng/ml throughout the study. Tacrolimus trough targets were 4–7 ng/ml during the first 3 months and 1.5–3 ng/ml (n = 107) or 4–7 ng/ml (n = 117) from Month 4. All patients received basiliximab induction and corticosteroids. The primary objective was to demonstrate superior estimated glomerular filtration rate (eGFR; MDRD‐4) at Month 12 in the tacrolimus 1.5–3 ng/ml versus the 4–7 ng/ml group. Secondary endpoints included incidence of biopsy‐proven acute rejection (BPAR; Months 4–12) and serious adverse events (SAEs; Months 0–12). Statistical significance was not achieved for the primary endpoint (mean eGFR: 57.1 vs. 51.7 ml/min/1.73 m2), potentially due to overlapping of achieved tacrolimus exposure levels (Month 12 mean ± SD, tacrolimus 1.5–3 ng/ml: 3.4 ± 1.4; tacrolimus 4–7 ng/ml: 5.5 ± 2.0 ng/ml). BPAR (months 4–12) and SAE rates were comparable between groups (2.7% vs. 1.1% and 58.7% vs. 51.3%; respectively). Everolimus‐facilitated tacrolimus minimization, to levels lower than previously investigated, achieved good renal function, low BPAR and graft‐loss rates, and an acceptable safety profile in renal transplantation over 12 months although statistically superior renal function of the 1.5–3 ng/ml tacrolimus group was not achieved. (ClinicalTrials.gov: NCT00369161) is registered at .

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1432-2277.2012.01465.x

Affiliations: 1:  Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary 2:  Department of Nephrology, University Medical Centre, Utrecht, The Netherlands 3:  Institute of Clinical and Experimental Medicine, Transplant Centre, Prague, Czech Republic 4: Division of Nephrology, Department of Internal Medicine, Academisch Ziekenhuis Maastricht, Maastricht, The Netherlands 5: Division of Nephrology, Hospital do Rim e Hipertensâo, São Paulo, Brazil 6: Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland 7: Service de Néphrologie, Hôpital Pasteur, CHU Nice, France 8: Department of Nephrology-Dialysis-Organ Transplantation, Hôpital Rangueil, Toulouse, France 9: Departamento de Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 10: Novartis Pharma AG, Basel, Switzerland 11: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA 12: Servicio de Nefrología, Hospital del Mar, Barcelona, Spain

Publication date: May 1, 2012

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