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.
Benítez
C E
CE
Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain.
Puig-Pey
I
I
López
M
M
Martínez-Llordella
M
M
Lozano
J J
JJ
Bohne
F
F
Londoño
M C
MC
García-Valdecasas
J C
JC
Bruguera
M
M
Navasa
M
M
Rimola
A
A
Sánchez-Fueyo
A
A
D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016559:Tacrolimus