Everolimus and Low-Dose Tacrolimus After Heart Transplant in Children: A Randomized Clinical Trial.
Almond, C. S., et al.Jama. 2025 Oct 21;334(15):1339-1348.
Aims
The aim of this study was to examine the role of everolimus plus low-dose tacrolimus in the prevention of major adverse transplant events (MATEs) in paediatric heart transplant recipients.
Interventions
Participants were randomly assigned to receive either everolimus and low-dose tacrolimus or standard-dose tacrolimus with mycophenolate mofetil.
Participants
211 paediatric heart transplant recipients with 6-month survival receiving stable immunosuppression at enrollment.
Outcomes
The primary efficacy outcome was 30-month MATE-3 score.The MATE-6 score was the primary safety outcome, which was a combination of the MATE-3 score, antibody-mediated rejection, infection and posttransplant lymphoproliferative disorder.
Follow-up
30 months after randomisation
CET Conclusions
This multicentre randomised trial randomised children 6 months following heart transplant to either continue tacrolimus and MMF, or switch to everolimus and low-dose tacrolimus. The study recruited 211 children, and used a composite endpoint of cellular rejection, cardiac allograft vasculopathy and chronic kidney disease at 30 months. There was no difference in primary efficacy or safety outcomes between the groups, although there was a lower incidence of CMV infection in the everolimus group. The authors should be congratulated as studies of this nature and size are challenging, due to the number of centres involved and the relatively small number of patients per centre. Study methodology was good, with random block randomisation providing allocation concealment and intent-to-treat as the primary analysis. The study was open-label, but assessment of the MATE endpoints was undertaken by an independent clinical events committee blinded to treatment allocation. Overall, the study provides compelling evidence that everolimus and low-dose tacrolimus is a safe alternative to a standard Tac/MMF regime in paediatric heart recipients, albeit with limited clinical benefit.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT03386539