A Double-blind, Double-dummy, Flexible-design Randomized Multicenter Trial: Early Safety of Single- vs. Divided-dose Rabbit Anti-thymocyte Globulin Induction in Renal Transplantation.
Stevens RB, Wrenshall LE, et al.American Journal of Transplantation 2015 [record in progress].
Aims
To evaluate single-dose rabbit anti-thymocyte globulin induction (SD-rATG) vs. conventional divided-dose (DD-rATG) induction for non-inferiority in early safety and tolerability.
Interventions
Participants were randomized to receive either 6 mg/kg SD-rATG, or 1.5 mg/kg/dose DDrATG, with tacrolimus/mycophenolate maintenance immunosuppression.
Participants
95 patients undergoing renal transplantation
Outcomes
The primary outcome measured was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary outcomes included 12month patient survival, graft survival, rejection, hematology findings, and infectious/non-infectious adverse events.
Follow-up
12 months
CET Conclusions
This is an interesting study from 4 transplant centres in the USA comparing a single (larger) dose versus multiple (smaller) doses of rATG as induction immune suppression for renal transplantation. In order to maintain the blinding, the coordinators scheduled regimens of active and placebo infusions for patients in both arms, so that it was effectively double blinded. It was designed as a non-inferiority study to check that the larger dose did not result in 20% more adverse events in the first 7 days. These infusion reactions, DGF and cardiac events contributed to a combined composite endpoint. Importantly the study was closed early at a planned interim analysis. At this stage it was calculated that there was <2% chance that any conclusion other than non-inferiority would be reached at the full inclusion analysis. This does weaken the conclusions about longer term equivalence. However, in the 12 month follow up there were only 5 patients with BPAR in each group and one episode of severe rATG reaction in the single-dose group. The divided-dose group experienced more errors of administration and more cases of thrombocytopaenia.
Data analysis
Modified intention-to-treat analysis
Trial registration
Clinicaltrials.gov - NCT00906204