SYMPHONY 2007.

Methods	Design: open‐label RCT Duration: November 2002 to November 2004 Follow up: 1 year
Participants	Setting: international multicentre (83 centres in 15 countries) Country: Turkey, Germany, Spain, Switzerland, Sweden, Belgium, USA, Canada, Israel, Czech Republic, Australia, Austria, Brazil, Poland, Mexico 1st or 2nd LD or DD transplant; aged 18 to 75 years Number (randomised/analysed): 1645/1589. group 1 (410/390); group 2 (413/399); group 3 (411/401); group 4 (411/399) Mean age ± SD (years): group 1 (45.9 ± 13.8); group 2 (47.2 ± 13.5); group 3 (45.4 ± 14.7); group 4 (44.9 ± 14.5) Sex (M/F): group 1 (255/155); group 2 (274/139); group 3 (270/141); group 4 (274/137) Exclusions: history of malignancy, PRA >20%, transplants of kidneys with >30 hr of cold ischaemia, non‐heart beating donor, need for other immunosuppressive therapy, active liver disease, history of cancer, active peptic ulcer, severe anaemia, leucopenia, thrombocytopenia, previous treatment with daclizumab/basiliximab
Interventions	Treatment group 1 sCSA: 6 to 10 mg/kg/d for trough levels 150 to 300 ng/mL months 0 to 3; then 100 to 200 ng/mL Treatment group 2 rCSA: 2 to 4 mg/kg/d for trough levels 50 to 100 ng/mL Treatment group 3 rTAC: 0.1 mg/kg/d for trough levels 3 to 7 ng/mL Treatment group 4 rSRL: 9 mg/d for 3 days, then 3 mg/d for trough level 4 to 8 ng/mL Co‐interventions Daclizumab MMF Steroids
Outcomes	eGFR at 12 months (primary outcome) Death Acute rejection Graft loss DGF Infections Malignancy Adverse reactions
Notes	Comparison is TOR‐I versus CNI by comparing group 4 with 1, 2 and 3 combined ITT group received transplant and treatment. ITT results reported for all outcomes except infections and adverse reactions
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients underwent randomisation... with the use of a centralized interactive voice response system (ClinIT)"
Allocation concealment (selection bias)	Low risk	Quote: "Patients underwent randomisation... with the use of a centralized interactive voice response system (ClinIT)"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary outcome was eGFR; laboratory outcome so unlikely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	3% randomised patients not included in ITT analyses
Selective reporting (reporting bias)	Low risk	Expected outcomes for this review (death, graft loss and acute rejection) have been reported. No protocol but outcomes specified in methods reported in results
Other bias	High risk	Funding for the study was provided by Hoffmann‐La Roche