Study conducted at Queen Elizabeth Hospital, Birmingham, UK
Renal function, efficacy and safety postconversion from twice- to once-daily tacrolimus in stable liver recipients: an open-label multicenter study
Version of Record online: 13 JAN 2012
© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation
Volume 25, Issue 3, pages 283–293, March 2012
How to Cite
Sańko-Resmer, J., Boillot, O., Wolf, P. and Thorburn, D. (2012), Renal function, efficacy and safety postconversion from twice- to once-daily tacrolimus in stable liver recipients: an open-label multicenter study. Transplant International, 25: 283–293. doi: 10.1111/j.1432-2277.2011.01412.x
Conflicts of interest J. Sanko Resmer, O. Boillot and D. Thorburn have no conflicts of interest to disclose. P. Wolf has received research grants from Astellas Pharma.
- Issue online: 7 FEB 2012
- Version of Record online: 13 JAN 2012
- Received: 9 February 2011 Revison requested: 3 March 2011 Accepted: 29 November 2011 Published online: 13 Janury 2012
- hepatic transplantation;
- phase III;
- prolonged release
This multicenter, open-label, phase III study assessed renal function, safety, and efficacy in stable adult liver transplant recipients converted from tacrolimus twice-daily (BID) to once-daily (QD). Patients received tacrolimus BID for 6 weeks before conversion to tacrolimus QD (1:1 [mg:mg] total daily dose basis) for 12 weeks. Primary endpoint: change in steady state creatinine clearance (CrCl) between treatment phases. Of 112 patients enrolled, 98 were converted to QD dosing (full analysis set [FAS]). Mean (SD) tacrolimus dose was 3.7 (1.7) mg/day during BID and at conversion, and 3.9 (1.8) mg/day at Week 12. 74.5% of patients required no dose adjustment on conversion (FAS). Mean tacrolimus whole blood trough levels were at the lower end of the recommended range during tacrolimus BID and QD; the difference between mean steady-state trough levels was statistically significant (7.5 ng/ml vs. 6.5 ng/ml; P < 0.0001). Following conversion, mean tacrolimus trough levels were reduced by 15% (about 1 ng/ml) without any cases of acute rejection, remained stable during the remainder of the study, and were more consistent, showing reduced between- and within-patient variability in trough levels. Renal function remained stable, demonstrating noninferiority of tacrolimus QD versus BID (relative difference in mean calculated CrCl −0.1% [±6.3%]). Patient and graft survival were 100%. Adverse events incidence was low during both treatment phases.