Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study.
Sterneck M, Kaiser GM, et al.Clinical Transplantation 2016 Jun;30(6):741-8.
Aims
To present the five year follow-up data from the PROTECT study* where de novo liver transplant recipients who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function.
Interventions
All eligible patients received basiliximab at Day 0 and Day 4 and thereafter CNI-based immunosuppression with or without corticosteroids. Between weeks 4 and 8, patients were randomized to receive either EVR (treatment group) or continue CNI (control group).
Participants
Adult patients receiving a liver transplant from a living or deceased donor were included in the PROTECT study. 81 patients who completed the core study and continued on their randomly assigned intervention were included in this analysis.
Outcomes
The primary outcomes measured were renal function, immunosuppressive efficacy, and safety.
Follow-up
5 years
CET Conclusions
This paper reports on the long term follow up from the PROTECT study, comparing everolimus to CNI in liver transplantation. Whilst the original study was a good randomised controlled trial there are some criticisms of this particular report. Key are the numbers entering and completing the study at various stages; the PROTECT study started with 375 randomisations, however only 81 entered into this extension study and only 53 of these completed the month 59 extension period. The report here is therefore much smaller than the original study and underpowered. Missing data were imputed as "last observation carried forward" but it is unclear how many patients had missing data. The authors used ANCOVA to adjust for centre effect. Unadjusted and adjusted eGFR change from baseline was significantly improved in the everolimus group when calculated by Nankivell or MDRD4. When using Cockcroft-Gault, the adjusted change was statistically significant, but not the unadjusted. The authors acknowledge that some caution should be used when extrapolating these results as only selected patients (without renal dysfunction and acute rejection) were migrated from the initial study to the extension study.
Data analysis
Available case analysis
Quality notes
Previously assessed as *Fischer L, et al. A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation— PROTECT. Am J Transplant 2012: 12: 1855.
Trial registration
Clinicaltrials.gov - NCT00378014