title: Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial.
abstract: BACKGROUND
  Results of studies in adult recipients of liver allograft suggest that tacrolimus is more efficacious than ciclosporin microemulsion in the prevention of acute rejection. We aimed to compare these drugs in children undergoing liver transplantation.
  
  
  METHODS
  This 12-month multicentre, open-label, parallel-group, randomised study compared a dual tacrolimus regimen (tacrolimus/corticosteroids, n=93) with a triple ciclosporin microemulsion regimen (ciclosporin microemulsion/corticosteroids/azathioprine, n=92) in children who had had liver transplants (age < or =16 years, bodyweight < or =40 kg). Initial oral daily doses were 0.30 mg/kg for tacrolimus and 10 mg/kg for ciclosporin microemulsion. Primary endpoint was the incidence of and time to first histologically proven acute rejection. We excluded patients from analysis if they did not receive the study drug, or were given incorrect medication. Otherwise patients were analysed in accordance with their random treatment allocation, irrespective of whether they switched medication during the trial.
  
  
  RESULTS
  Median age was 22 months (IQR 9-56) in the tacrolimus group and 17 months (9-54) in the ciclosporin microemulsion group. We noted no difference between treatment groups with respect to patient survival (93.4% vs 92.2%; p=0.77) or graft survival (92.3% vs 85.4%; p=0.16) at month 12 after transplant. The acute rejection free rate at study end (Kaplan-Meier method) was 55.5% for patients on tacrolimus and 40.2% for patients on ciclosporin microemulsion (p=0.0288). The Kaplan-Meier estimate of patients free from corticosteroid-resistant acute rejection at study end was 94.0% for tacrolimus-treated patients and 70.4% for ciclosporin-microemulsion-treated patients (p<0.0001). Overall, incidence of adverse events did not differ between groups.
  
  
  CONCLUSIONS
  Tacrolimus is a safe and effective treatment for the prevention of rejection after liver transplantation in children.
authors.affiliation: Liver Unit, Birmingham Children's Hospital NHS Trust, Birmingham, UK. Deirdre.Kelly@bch.nhs.uk
authors.forename: Deirdre
authors.initials: D
authors.lastname: Kelly
authors.forename: Paloma
authors.initials: P
authors.lastname: Jara
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rodeck
authors.forename: Panayotis
authors.initials: P
authors.lastname: Lykavieris
authors.forename: Martin
authors.initials: M
authors.lastname: Burdelski
authors.forename: Michael
authors.initials: M
authors.lastname: Becker
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
authors.forename: Olivier
authors.initials: O
authors.lastname: Boillot
authors.forename: Javier
authors.initials: J
authors.lastname: Manzanares
authors.forename: Raymond
authors.initials: R
authors.lastname: Reding
mesh_terms: D000284:Administration, Oral; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D004655:Emulsions; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004655:Emulsions; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine; D016559:Tacrolimus