Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal.Tonshoff, B., et al.
American Journal of Transplantation 2020 [record in progress].
This is a three-year follow up study of the CRADLE trial, which was an RCT investigating the safety and efficacy of of everolimus (EVR) + reduced-exposure tacrolimus (rTAC) with early steroid withdrawal at 6 months following transplant in pediatric renal transplant patients. The primary objective of this study was to assess the mid-term outcomes of the EVR + rTAC regimen in this pediatric population.
All participants entered a run-in period in which they were given mycophenolate mofetil (MMF) + standard-exposure TAC (sTAC) as well as corticosteroids. They were subsequently randomized to either switch to EVR + rTAC with early corticosteroid withdrawal at 6-month posttransplant or to continue MMF+sTAC with corticosteroids.
106 randomized kidney transplant recipients.
The primary outcomes were the incidence of composite efficacy failure (death, graft loss or biopsy-proven acute rejection (BPAR)) as well as its individual components, acute rejection (AR), severity and timing of BPAR and antibody-mediated BPAR. The secondary outcomes included statural growth including height, weight and body mass index (BMI), and pubertal development.
This is a good quality randomised controlled trial in paediatric renal transplantation (106 patients). Neither patients nor assessors were blinded to the treatment allocation. The early follow up results have previously been published, and showed little difference between the two regimens. This longer term follow up also shows little significant difference between the 2 groups for major events, with similar rates for the composite efficacy outcome (biopsy-proven acute rejection [BPAR], graft loss, or death): 9.8% versus 9.6%. Mean GFR at 36 months, as well as changes in height and weight were similar. However, Everolimus + tacrolimus regimen was associated with significantly higher rates of pyrexia (38.5% vs. 22.2%), nasopharyngitis (30.8% vs. 11.1%), aphthous ulceration (19.2% vs. 1.9%), transplant rejection (19.2% vs. 11.1%), and Epstein-Barr virus (EBV) infection (13.5% vs. 3.7%) than MMF + tacrolimus. Everolimus + tacrolimus was also associated with significantly lower rate of neutropenia (5.8% vs. 20.4%) and cytomegalovirus infections (7.7% vs. 16.7%). Study drug discontinuation was significantly higher in the everolimus + tacrolimus group (25.0% vs. 11.1%), this difference mostly being due to difference in acute rejection rates.
ClinicalTrials.gov - NCT01544491