Flechner 2013.

Methods	Design: parallel RCT; 2:1 randomisation Study duration: June 2005 ‐ June 2006: study recruitment stopped after about 12 months by data monitoring committee because of a high rate of acute rejection Duration of follow‐up: 206 patients completed 6 months follow‐up. Originally planned for 2‐year follow‐up
Participants	Setting: multicentre transplant services Countries: USA, Spain, Australia, Canada, Turkey, Hungary, South Africa, Italy, Greece, Argentina, Chile, UK, Sweden De novo kidney transplant recipients aged > 13 years; DD, LD (non HLA identical); WBC ≥ 4000 mm3; platelets ≥ 100,000 mm3; cholesterol ≤ 300 mg/dL, triglycerides ≤ 350 mg/dL Number (group 1/group 2): ITT population (randomised and received transplant) 475 (314/161); safety population 471 (received at least one dose of medication) Mean age ± SD (years): group 1 (42.9 ± 14.2); group 2 (42.7 ± 11.8) Sex (M/F): group 1 (218/96); group 2 (116/45) Exclusions: donor organ with cold ischaemic time > 30 hours or those from non‐heart beating donors
Interventions	Treatment group 1 SRL: 10 to 15 mg within 48 hours of transplant then 4 to 8 mg/d for levels ≥ 10 ng/mL; doses for levels to week 13, 10 to 15 ng/mL; weeks 14 to 26, 8 to 12 ng/mL; weeks 27 to 104, 5 to 12 ng/mL After 6 months (Amendment 2), SRL loading dose of 15 mg x 2 & 10 mg daily until whole‐blood SRL trough levels were 10.0 ng/mL or more; to week 26, 10 to 15 ng/mL; weeks 27 to 104, 8 to 15 ng/mL Treatment group 2 CSA 6 to 8 mg/kg/dose; adjusted for levels to week 13, 150 to 300 ng/mL; weeks 14 to 26, 50 to 200 ng/mL; weeks 27 to 104, 50 to 150 ng/mL Co interventions Basiliximab: 20 mg on day of transplant and day 4 MMF: 2 g/d started within 48 hours MP/prednisolone
Outcomes	Graft survival Patient survival BPAR GFR
Notes	Comparison: TOR‐1 versus CNI Note study terminated prematurely due to high rate of acute rejection in the SRL group. 127 patients receiving SRL and 79 receiving CSA completed 6 months of treatment
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomly assigned (2:1) by a computerized randomisation/enrolment system
Allocation concealment (selection bias)	Low risk	Patients were randomly assigned (2:1) by a computerized randomisation/enrolment system
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary outcomes were BPAR and GFR; unlikely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	Study terminated prematurely because of increased risk of rejection in SRL group
Selective reporting (reporting bias)	Low risk	Expected outcomes reported
Other bias	High risk	Sponsored by Wyeth. Authors were employees/received funding from drug companies