Conversion from tacrolimus to everolimus with complete and early glucocorticoid withdrawal after kidney transplantation: a randomised trial.Bouamar R, Shuker N, et al.
Netherlands Journal of Medicine 2018; 76(1): 14-26.
To determine the safety and tolerability of switching from tacrolimus to everolimus with glucocorticoid withdrawal after living-donor kidney transplantation.
Participants were randomised to either continue tacrolimus or to switch to everolimus-based maintenance immunosuppressive therapy.
60 adult patients aged ≥ 18 years who received a blood group AB0-compatible kidney transplant from a living donor (excluding HLA-identical siblings), and treated with immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil and prednisolone at month 3 after transplantation.
The primary outcome measured was renal function at month 12 ± 6 weeks after transplantation. Secondary measured outcomes included graft survival, the incidence of biopsy-proven acute rejection, adverse events, serious adverse events and renal histology on protocol biopsy.
This single-centre, open-label randomised controlled trial evaluated the efficacy of continued tacrolimus versus everolimus with complete glucocorticoids withdrawal in adult kidney transplant recipients who were on tacrolimus, MMF and prednisolone and received an ABO blood type compatible transplant from a living donor. A random-number generator generated the randomisation sequence and patients were randomised using sealed, opaque envelopes at three months posttransplant. The sample size calculation was based on eGFR and showed that 194 patients had to be included to achieve 90% power, accounting for a drop-out rate of 30%. The trial was terminated after the first interim analysis when 60 patients had been included because of the high incidence of biopsy-proven acute rejection (30% vs 6.7%) and high re-conversion rate to tacrolimus (60%) in the everolimus group. The underpowered, primary (intention to treat) analysis showed no difference in eGFR between groups at 12 months. There was a higher incidence of adverse events in the everolimus group compared to the tacrolimus group. The authors conclude that conversion from tacrolimus to everolimus at three months after transplantation with complete withdrawal of glucocorticoids is not safe in living-donor kidney transplant recipients.
Dutch National Trial Registry - NTR2545