Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients.
Tedesco-Silva H, Peddi VR, et al.Transplantation Direct 2016; 2(4): e69.
Aims
To evaluate the effect of early transition from tacrolimus (TAC) to sirolimus (SRL) on renal function in renal allograft recipients.
Interventions
Between 90 and 150 days after renal transplantation, participants were randomized to either transition from TAC to SRL, or continue TAC-based therapy for 19 to 21 months.
Participants
256 patients aged ≥ 18 years receiving a primary renal allograft from a living or deceased donor.
Outcomes
The primary outcome measured was the percentage of patients with 5mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate (eGFR) at 24 months posttransplantation. Secondary outcomes included percentage of patients with eGFR improvement at 12 months, change in eGFR, percentage of patients with Up/c 0.5 or greater, composite rate of first occurrence of biopsy-confirmed acute rejection (BCAR), graft loss, or death, and treatment-emergent AEs (TEAEs), including infection, malignancy, and posttransplantation diabetes mellitus.
Follow-up
24 months
CET Conclusions
In this study renal transplant patients were transferred from tacrolimus to sirolimus therapy. A large number (44/131) had to discontinue sirolimus due to a combination of adverse events, whereas a relatively small number (12/123) discontinued tacrolimus. Even amongst the "on therapy" groups there was no significant increase in GFR comparing the two medications. Sirolimus was associated with significantly greater rates of rejection, mouth ulceration, dyslipidaemia, peripheral oedema and proteinuria. Tacrolimus was associated with higher rates of squamous cell carcinoma of the skin. The renal function in both groups improved on average over 24 months. Sirolimus may have a role in some patients, but comes with significant risks compared to tacrolimus if applied indiscriminately.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00895583