European Study 1994.

Methods	Generation of the allocation sequence: adequate. Randomly assigned to treatment within centres in blocks of 4, each block containing an equal number allocated to the 2 treatment groups; stratified for the presence of fulminant hepatic failure. Allocation concealment: adequate. Third party allocation. Blinding: not performed. Follow‐up: adequate.
Participants	Country: Eight centres in four European countries. Language: English. Inclusion criteria: Male and female patients, aged 18 to 70, undergoing primary isolated liver transplantation. Exclusion criteria / diagnoses: vasculitis, primary liver cancer with metastases, HIV, treatment with an investigational agent. Allocation: tacrolimus n = 264; cyclosporin n = 265.
Interventions	Tacrolimus protocol: ‐ 0.075 mg/kg IV over 4 hours q 12 h for 3 days then conversion to oral at 0.30 mg/kg/d ‐ during the study changes to the tacrolimus regimen resulted in a lower daily dose ‐ all tacrolimus patients also received IV methylprednisolone at 10 mg/kg intra‐op or post‐op (single dose) followed by 20 mg/d prednisolone or equivalent methylprednisolone if patient unable to take oral ‐ steroids tapered and withdrawal was acceptable. Cyclosporin protocol: ‐ cyclosporin formulation: oil‐based ‐ centre dependent ‐ 1 to 6 mg/kg IV or 8 to 15 mg/kg oral ‐ all cyclosporin patients also received azathioprine from 1 to 3 mg/kg, steroids from 0.5 to 2.0 mg/kg ‐ in three cantres the cyclosporin patients received ATG 5 mg/kg/d for 1 week . Concomitant immunosuppression: steroids to all patients; antithymocyte globulin to both groups at 3 centres; azathioprine to cyclosporin recipients according to local practice.
Outcomes	‐ patient survival ‐ graft survival ‐ acute rejection ‐ refractory rejection ‐ chronic rejection ‐ insulin dependent DM ‐ creatinine ‐ infection ‐ withdrawal ‐ impaired renal function ‐ neurologic complications ‐ hirsutism
Notes	Follow‐up: 12 months Other adverse events: tremor ‐ tacrolimus (127/264); cyclosporin (85/265) paraesthesia ‐ tacrolimus (45/264), cyclosporin (44/265) infection ‐ tacrolimus (99/264); cyclosporin (107/265) cytomegalovirus ‐ tacrolimus (41/264); cyclosporin (58/265) pneumonia ‐ tacrolimus (43/264); cyclosporin (56/265).
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate