Vitko‐TERRA 2004.

Methods	Design: open‐label RCT Duration: not reported Follow up: 6 months
Participants	Setting: multicentre (75 centres) Country: 15 European countries, Australia Kidney transplant recipients ≥ 18 years, 1st or 2nd grafts (unless immunological reason for previous graft loss) Number (group 1/group 2/group 3): 677 (325/325/327) Mean age ± SD (years): group 1 (44.6 ± 12.9); group 2 (47.3 ± 12.4); group 3 (46.0 ± 11.7) Sex (M/F): group 1 (211/114); group 2 (195/130); group 3 (219/108) Exclusions: PRA > 85%; liver disease; infection; severe cholesterolaemia; donor kidney ischaemia time > 40 hours; non‐heart beating donor; HBV, HCV or HIV +ve donor; malignancy; GI disorders; intolerance to study drugs
Interventions	Treatment group 1 SRL: single dose 1.5 mg then 0.5 mg/d then adjusted for levels Treatment group 2 SRL: single dose 6 mg then 2 mg/d then adjusted for levels Treatment group 3 MMF: 1 g/d Co‐interventions TAC: 0.2 mg/kg/d for levels 8 to 16 ng/mL (days 0 to 14) then 5 to 15 ng/mL Prednisolone
Outcomes	Death (all causes) Cause‐specific death Graft loss censored for death Graft loss or death with a functioning graft Acute rejection Steroid‐resistant rejection CrCl SCr Infection CMV infection Malignancy Haematological adverse effects Biochemical adverse effects Surgical adverse effects
Notes	Comparison: TOR‐I versus antimetabolite Comparison: low dose versus higher dose TOR‐I
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was 1:1:1 and was performed locally at each centre using sealed randomisation envelopes supplied by the study sponsor
Allocation concealment (selection bias)	Low risk	Randomisation was 1:1:1 and was performed locally at each centre using sealed randomisation envelopes supplied by the study sponsor
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcomes unlikely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	All patients accounted for
Selective reporting (reporting bias)	Low risk	Expected outcomes reported
Other bias	High risk	Sponsored by Fujiawa

ARB ‐ angiotensin receptor blocker; ATN ‐ acute tubular necrosis; ACEi ‐ angiotensin‐converting enzyme inhibitor; ALG ‐ antilymphocyte globulin; ATG ‐ antithymocyte globulin; AZA ‐ azathioprine; BMI ‐ body mass index; BP ‐ blood pressure; BPAR ‐ biopsy‐proven acute rejection; CAN ‐ chronic allograft nephropathy; CCB ‐ calcium channel blockers; CMV ‐ cytomegalovirus; CNI ‐ calcineurin inhibitor; CrCl ‐ creatinine clearance; CSA ‐ cyclosporin; DD ‐ deceased donor; ER ‐ extended release; ESKD ‐ end‐stage kidney disease; EVL ‐ everolimus; FSGS ‐ focal segmental glomerulosclerosis; (e)GFR ‐ (estimated) glomerular filtration rate; GI ‐ gastrointestinal; Hb ‐ haemoglobin; HbSAg ‐ hepatitis B surface antigen; HBV ‐ hepatitis B virus; HCV ‐ hepatitis C virus; HIV ‐ human immunodeficiency virus; HLA ‐ human leukocyte antigen; IL2 ‐ interleukin 2; ITT ‐ intention‐to‐treat; IV ‐ intravenous(ly); LD ‐ living donor; LRD ‐ living‐related donor; M/F‐ male/female; MI ‐ myocardial infarction; MMF ‐ mycophenolate mofetil; MP ‐ methylprednisolone; MPA ‐ mycophenolic acid; MPS ‐ mycophenolate sodium; NODM ‐ new‐onset diabetes mellitus; PRA ‐ panel reactive antibodies; r ‐ reduced dose (rCSA; rTAC); RCT ‐ randomised controlled trial; s ‐ standard dose (sCSA; sTAC); SCr ‐ serum creatinine; SD ‐ standard deviation; SRL ‐ sirolimus; TAC ‐ tacrolimus; TOR‐I ‐ target of rapamycin inhibitor; WBC ‐ white blood cells