Llado 2006.

Methods	Trial design: randomised, multicentre, open‐label clinical trial Mean follow‐up: not reported Study duration: randomisation between April 2001 and September 2004, 6 months from randomisation (longer for HCV‐positive patients) Language: English Type of information: journal article Judgement on quality: high risk
Participants	Setting: 7 transplantation centres in Spain Allocation of participants: 198 participants, 102 allocated to Intervention A, 96 allocated to Intervention B Sex ratio: total: 155 (78.3%) males, 43 (21.7%) females Intervention A: 80 (78.4%) males, 22 (21.6%) females Intervention B: 75 (78.1%) males, 21 (21.9%) females Mean age: total: not reported Intervention A: 55.4 ± 8.9 Intervention B: 52.9 ± 9.5 Indication (no. (%)): HCC: total: 63 (31.8%), Intervention A: 34 (33.3%), Intervention B: 29 (30.2%) HCV cirrhosis: total: 46 (23.2%), Intervention A: 20 (19.6%), Intervention B: 26 (27.1%) HBV cirrhosis: total: 14 (7.1%), Intervention A: 8 (7.8%), Intervention B: 6 (6.3%) Alcoholic cirrhosis: total: 55 (27.8%), Intervention A: 29 (28.4%), Intervention B: 26 (27.1%) Other: total: 20 (10.1%), Intervention A: 11 (10.8%), Intervention B: 9 (9.4%) Type of donor: deceased donor Inclusion criteria: liver transplant recipients from cadaveric donors aged > 18 Exclusion criteria: exclusion criteria: transplant for fulminant liver disease, retransplant, previous or concurrent other organ transplant, autoimmune hepatitis, primary biliary cirrhosis, HIV infection, likely poor compliance Other: Disease status: HCV‐positive recipient: total: 88 (44.4%), Intervention A: 45 (44.1%), Intervention B: 43 (44.8%) CMV‐positive recipient: total: 165 (83.3%), Intervention A: 83 (81.3%), Intervention B: 82 (85.4%) Diabetes mellitus pretransplant: total: 49 (24.7%), Intervention A: 28 (27.5%), Intervention B: 21 (21.9%) Glycated haemoglobin pretransplant: total: not reported, Intervention A: 4.9 ± 1.5, Intervention B: 4.6 ± 0.9 Hypertension pretransplant: total: 17 (8.6%), Intervention A: 11 (10.8%), Intervention B: 6 (6.3%) Serum cholesterol pretransplant: total: not reported, Intervention A: 3.8 ± 1.2, Intervention B: 4.0 ± 1.3 (%)
Interventions	Intervention A: no intervention Intervention B: hydrocortisone: 500 mg intraoperatively, then 0.5 mg/kg/day for days 1 to 5, 0.25 mg/kg/day for days 6 to 30, 0.15 mg/kg/day for days 31 to 90, no intervention from day 91 Concomitant immunosuppression: Basiliximab: 20 mg intraoperatively Cyclosporine A: started at 10 mg/kg/day aiming for trough levels of 800 ng/mL to 1200 ng/mL
Outcomes	Mortality, graft loss, acute rejection, glucocorticosteroid‐resistant rejection, chronic rejection, adverse events, infections, bacterial infection, viral infection, fungal infection, CMV infection, HSV infection, metabolic decompensations, diabetes mellitus, hypertension, recurrent hepatitis C, treatment failure, renal failure, neurological deficit, gingival hypertrophy, de novo malignancy, cholesterol, triglyceride, days until rejection
Notes	Cross‐over between intervention arms: no Sample size calculation: yes Sources of funding: Novartis Pharma, TV3 Marathon Foundation
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: Generation of randomisation sequence not described
Allocation concealment (selection bias)	Unclear risk	Comment: Allocation concealment not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote from the publication: "The trial was an open‐label, not‐blinded, prospective, randomized study." Comment: Blinding of participants and medical staff not performed
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote from the publication: "The trial was an open‐label, not‐blinded, prospective, randomized study." Comment: Blinding of outcome assessors not performed
Incomplete outcome data (attrition bias)	Unclear risk	Quote from the publication: "Two patients were exclude from the study after randomization because of protocol violations." Comment: The protocol violations are not described and the groups to which these patients were randomised is not described. Otherwise, the number of withdrawals and reasons for withdrawal not reported
Selective reporting (reporting bias)	Low risk	Comment: All outcomes appear to be fully reported
Other bias	High risk	Quote from the publication: "The authors who have taken part in this study have declared a relationship with the manufacturers of the drugs involved and they received funding from the drug companies involved to carry out their research." Quote from the publication: "We are grateful to Infociencia Clinical Research for monitoring the study, and especially thank Cati Bonet for the statistical analysis. This research was supported by Novartis Pharma, and by the TV3 Marathon Foundation." Comment: Study is partly industry sponsored
Free of early stopping?	Low risk	Comment: Study not stopped early
Free of baseline imbalance?	Low risk	Quote from the publication: "Patient demographics and baseline characteristics were similar between groups (Table 1). It should be noted that 45% of patients were HCV‐positive. Main operative and initial post‐operative evolution was also similar between groups (Table 2)". Comment: Study free from baseline imbalance