Renal
Candidate
Once-a-Day Administration of Everolimus Is Safe in De Novo Renal Transplant Recipients: 1-Year Results of a Pilot Study

https://doi.org/10.1016/j.transproceed.2011.03.018Get rights and content

Abstract

Introduction

The half-life of everolimus is approximately 28 hours, but everolimus is generally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation.

Methods

Forty-one de novo renal transplant recipients prospectively assigned to OD (n = 21) or BID (n = 20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression.

Results

At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL (P = NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, (P = NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL (P < .001).

Discussion

This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes.

Section snippets

Methods

This study was performed on patients who signed an informed consent form, using immunosuppressive protocols approved by our ethical committee. This prospective, consecutive group clinical study enrolled 41 adult male and nonpregnant female patients who underwent primary kidney transplantation from a deceased donor between 2006 and 2009. We excluded recipients with a historical or current peak panel-reactive antibodies > 50%; cold ischemia time > 24 hours; thrombocytopenia (platelets < 75,000/mm3

Results

Forty-one de novo deceased donor kidney transplant recipients were enrolled in the study: 21 patients were allocated to the OD and 20 to the BID group. All patients completed the 1-year observation period.

The demographic characteristics of the two groups of patients were not significantly different at baseline for sex, time on dialysis, cold ischemia time, human leukocyte antigen mismatch, body mass index, dyslipidemia, hypertension, and diabetes mellitus. Age at transplant and donor age were

Discussion

In this prospective clinical study of de novo deceased donor kidney transplant recipients, we showed that once a day administration of everolimus provided excellent patient and graft survival as well as good renal function without an increased incidence of acute rejection episodes and a similar safety profile as twice a day everolimus administration.

Pharmacokinetic studies in the clinical development phase of everolimus already showed the basis for the once a day administration of everolimus.

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