Efficacy and Safety of Low-Dose Cyclosporine with Everolimus and Steroids in de novo Heart Transplant Patients: A Multicentre, Randomized Trial

Andreas Zuckermann, Shoei-Shen Wang, Heather Ross, Maria Frigerio, Howard J Eisen, Christoph Bara, Daniel Hoefer, Maurizio Cotrufo, Gaohong Dong, Guido Junge, Anne M Keogh, Andreas Zuckermann, Shoei-Shen Wang, Heather Ross, Maria Frigerio, Howard J Eisen, Christoph Bara, Daniel Hoefer, Maurizio Cotrufo, Gaohong Dong, Guido Junge, Anne M Keogh

Abstract

A six-month, multicenter, randomized, open-label study was undertaken to determine whether renal function is improved using reduced-exposure cyclosporine (CsA) versus standard-exposure CsA in 199 de novo heart transplant patients receiving everolimus and steroids ± induction therapy. Mean C(2) levels were at the low end of the target range in standard-exposure patients (n = 100) and exceeded target range in reduced-exposure patients (n = 99) throughout the study. Mean serum creatinine at Month 6 (the primary endpoint) was 141.0 ± 53.1 μmol/L in standard-exposure patients versus 130.1 ± 53.7 μmol/L in reduced-exposure patients (P = 0.093). The incidence of biopsy-proven acute rejection ≥3A at Month 6 was 21.0% (21/100) in the standard-exposure group and 16.2% (16/99) in the reduced-exposure group (n.s.). Adverse events and infections were similar between treatment groups. Thus, everolimus with reduced-exposure CsA resulted in comparable efficacy compared to standard-exposure CsA. No renal function benefits were demonstrated; that is possibly related to poor adherence to reduced CsA exposure.

Figures

Figure 1
Figure 1
Patient disposition.
Figure 2
Figure 2
CsA C2 level during the six-month study. Shaded areas indicate target C2 ranges (hatched area, shared target to Day 59; dark area, reduced-CsA; light area, standard-CsA). Values are shown as mean±SD (central laboratory results).
Figure 3
Figure 3
Serum creatinine during the six-month study (ITT population). Values shown are mean ± SD.

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Source: PubMed

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