Moench 2007.

Methods	Trial design: randomised, double‐blinded, placebo‐controlled, single‐centre clinical trial Mean follow‐up: not reported as all patients followed up at 5 years, except deaths Study duration: 5 years from randomisation, randomisation from February 2000 to July 2004 Language: English Type of information: journal article Judgement on quality: high risk
Participants	Setting: Johannes Gutenberg University Mainz Hospital, Langenbeckstrasse 1, Mainz, Germany Allocation of participants: 110 participants, 54 allocated to Intervention A, 56 allocated to Intervention B Sex ratio: total: 74 (67.3%) males, 36 (32.7%) females Intervention A: 36 (66.7%) males, 18 (33.3%) females Intervention B: 38 (67.9%) males, 18 (32.1%) females Mean age: total: not reported Intervention A: 53.5 ± 8.3 Intervention B: 53.6 ± 10.4 Indication (no. (%)): Hepatocellular carcinoma: total: 40 (36.4%), Intervention A: 19 (35.2%), Intervention B: 21 (37.5%) HBV cirrhosis: total: 19 (17.3%), Intervention A: 7 (13.0%), Intervention B: 12 (21.4%) HCV cirrhosis: total: 31 (28.2%), Intervention A: 15 (27.8%), Intervention B: 16 (28.6%) Alcoholic cirrhosis: total: 37 (33.6%), Intervention A: 21 (38.9%), Intervention B: 16 (28.6%) Primary biliary cirrhosis or primary sclerosing cholangitis: total: 8 (7.3%), Intervention A: 5 (9.3%), Intervention B: 3 (5.4%) Type of donor: deceased donor after brain death (DBD) or living‐related donor Inclusion criteria: orthotopic liver transplant recipients aged > 18 receiving transplant for any indication, recipients of whole or partial liver grafts from brain dead donors as well as living‐related donors, oral informed consent Exclusion criteria: previous organ transplants including liver retransplantation; initial, sequential or parallel therapy with other immunosuppressive drugs besides the study protocol; corticosteroid therapy within 6 months before transplantation; HIV infection; pregnancy and breast feeding; allergy to or intolerance of study medication; participation in another clinical study Other: Partial graft: total: 6 (5.5%), Intervention A: 3 (5.6%), Intervention B: 3 (5.4%) Deceased donor: total: 100 (90.9%), Intervention A: 50 (92.6%), Intervention B: 50 (89.3%) Living donor: total: 10 (9.1%), Intervention A: 4 (7.4%), Intervention B: 6 (10.7%)
Interventions	Intervention A: matched placebo Intervention B: methylprednisolone: 12 mg/day from day 15 to 60, 8 mg/day from day 61 to 180 then tapered to stop over 2 weeks Concomitant immunosuppression: Tacrolimus: initial dose of 0.01 mg/kg/day with target trough levels 10 to 15 ng/mL for days 0 to 42 and 5 ng/mL to 10 ng/mL thereafter Methylprednisolone: 1000 mg before reperfusion, 100 mg on day 1, 75 mg on day 2, 48 mg on day 3 and 4, 36 mg on day 5 and 6, 24 mg on day 7 and 8, 16 mg on days 9 to 13 and 12 mg on day 14
Outcomes	Mortality, graft loss, acute rejection, time to first rejection, severity of rejection, recurrent acute rejection, glucocorticosteroid‐resistant rejection, chronic rejection, hypertension, diabetes mellitus, infection, CMV infection, post‐transplant lymphoproliferative disorder, hypercholesterolaemia, hypertriglyceridaemia, osteoporosis, cholesterol, triglyceride, creatinine, HDL cholesterol, LDL cholesterol, fasting blood glucose, neurological toxicity, abnormal liver function, abnormal renal function.
Notes	Cross‐over between intervention arms: no Sample size calculation: yes Sources of funding: Astellas Pharma Munich, Germany
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)	Low risk	Quote from the publication: "Patient care and study conduct complied with good clinical practice.1:1 randomization was performed by a blinded randomization list generated by the Biomathematical Institute prior to transplantation in eligible patients (Figure 1)." Comment: Allocation concealment not fully described, however, the publication describes the randomisation sequence as "blinded" in addition to the blinding or participants and outcome assessors described elsewhere
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote from the publication: "This was a 12‐month, prospective, randomized, double‐blinded, placebo‐controlled investigator driven, monocenter trial comparing early FK506 monotherapy with FK506 plus steroids." Quote from the publication: "After day 14, patients received study medication, either placebo or methylprednisolon capsules in a double‐blinded way. Study medication was manufactured, packed and blinded by the Pharmacy Department of Johannes Gutenberg University Hospital." Quote from the publication: " Patients who experienced three or more episodes of acute rejection during the follow‐up were excluded from the trial, unblinded and received individualized immunosuppressive therapy. Comment: Double‐blinded trial, both participants and medical staff blinded to treatment
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: Blinding of pathologists not described
Incomplete outcome data (attrition bias)	Low risk	Quote from the publication: "The number of patients completing the follow‐up were 35 (66.7%) in the steroid group and 36 (62.5%) in the placebo group (p = 0.801, chi‐square). Reasons for withdrawal from the trial were death (n = 14, 12.7%), recurrent rejection (n = 11, 10.0%), severe adverse events (n = 10, 9.1%) and secondary refusal to informed consent (n = 1, 0.9%)." Quote from the publication: "Fourteen (12.7%) patients died during follow‐up, 6 (11.1%) in the steroid group and 8 (14.3%) in the placebo group (p = 0.617, chi‐square). At month 6, 46 patients were still in the steroid and the placebo group. Eight patients were withdrawn from the steroid group and 10 patients were withdrawn from the placebo group during the first 6 months. At month 12, 35 patients were still in the steroid group and 36 patients were still in the placebo group. Eleven patients were withdrawn from the steroid group and 10 patients were withdrawn from the placebo group during month 6 until month 12." Comment: The numbers and reasons for dropouts are adequately described
Selective reporting (reporting bias)	Low risk	Comment: All outcomes appear to be fully reported
Other bias	High risk	Quote from the publication: "The study was supported by Astellas Pharma Munich, Germany." Comment: Study is industry sponsored
Free of early stopping?	Low risk	Comment: Study not stopped early
Free of baseline imbalance?	Low risk	Quote from the publication: "Patientsdemographicsandbaselinecharacteristics were comparable in both groups and are demonstrated in Table 1." Comment: Study free from baseline imbalance