ATG‐Fresenius Treatment and Low‐Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver Transplantation

We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG‐Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard‐dose tacrolimus plus steroids;or (b) peritransplant ATG‐Fresenius plus reduced‐dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end‐point was the achievement of very low‐dose tacrolimus (every‐other‐day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end‐point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG‐Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance‐related biomarkers were observed. In conclusion, the use of ATG‐Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier:NCT00436722.