Efficacy and safety of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus.Vondrak, K. et al. (2019).
Clinical Transplantation [record in progress].
To compare efficacy and safety of immediate‐release tacrolimus (IR‐T) vs prolonged‐release tacrolimus (PR‐T) in de novo kidney, liver, and heart transplant recipients.
Patients were randomized to receive either prolonged‐release tacrolimus or immediate‐release tacrolimus within 4 days of surgery.
44 solid organ transplant recipients.
Safety, efficacy, and tacrolimus trough level data were obtained during follow‐up visits on Day 60, 90, 180, and 365. The efficacy endpoints after 365 days measured the number of clinical acute rejections, BCAR episodes (including severity), patient and graft survival, and efficacy failure (a composite endpoint of death, graft loss, BCAR, or unknown outcome).
Given that there is little information published about prolonged release tacrolimus in paediatric transplant patients so this is an important Phase-2, open-label, study. It included recipients of heart, kidney and liver transplants randomised to immediate-release (twice daily) or prolonged-release (once-daliy) tacrolimus. The early (4-week) pharmacokinetic study has previously been published and this paper concentrates on the longer-term follow up at 1 year. Each centre was able to give the rest of their routine immune suppression regimen as required. Over one year of follow up the mean tacrolimus doses and trough levels were similar between the two arms of the study. In the prolonged-release arm there was 1 case of biopsy confirmed rejection (BCAR) in a liver recipient and 1 case of clinical rejection in a heart recipient. In the immediate-release arm there were 4 cases of BCAR in liver recipients, 1 case of clinical rejection in a heart recipient and 2 kidney recipients. There were no cases of graft loss or death during the study period. There was no significant difference in the composite end-point of “efficacy failure” although it appeared to favour the prolonged-release preparation. However, this was due to the inclusion of patients with unknown outcome that left the study early (removed consent, other adverse outcome, non-compliant with study visits). There was no significance in overall adverse events or drug-related adverse events. It should be noted that the study targeted older children and hence the median age is 10.6 years and 95% were Caucasian.
ClinicalTrials.gov - NCT01614665