De novo sirolimus and reduced-dose tacrolimus versus standard-dose tacrolimus after liver transplantation: the 2000-2003 phase II prospective randomized trial.
Am J Transplant
; 14(2): 356-66, 2014 Feb.
Article
in En
| MEDLINE
| ID: mdl-24456026
ABSTRACT
We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough 7-15 ng/mL) or sirolimus (loading dose 15 mg, initial dose 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Liver Transplantation
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Tacrolimus
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Sirolimus
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Graft Rejection
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Graft Survival
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Immunosuppressive Agents
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Liver Diseases
Type of study:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Am J Transplant
Journal subject:
TRANSPLANTE
Year:
2014
Document type:
Article