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. 2019 Dec 16;2019(12):CD004290. doi: 10.1002/14651858.CD004290.pub3

TRANSFORM 2018.

Methods

  • Design: open‐label RCT

  • Duration: December 2013 to January 2016

  • Follow up: 12 months
Participants

  • Setting: multicentre (186 centres)

  • Countries: 42 countries (Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Colombia, Croatia, Czech, Egypt, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Kuwait, Lebanon, Malaysia, Mexico, Netherlands, Norway, Philippines, Poland, Portugal, Russia, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, USA)

  • Participants: de novo kidney transplant recipients, LD or DD

  • Number (group 1/group 2): 2037 (1022/1015)

  • Mean age ± SD (years): group 1 (49.3 ± 14.1); group 2 (49.3 ± 14.5)

  • Sex (M/F): group 1 (710/315): group 2 (707/308)

  • Exclusions: HLA identical or expanded criteria DD; positive cytotoxic cross‐match or PRA ≥ 50%; HCV infection in donor/recipient; cold ischaemia time > 30 hours
Interventions Treatment group 1 (EVL/rCNI)

  • EVL: 1.5 mg twice/day for TAC recipients & 0.75 mg twice/day for CSA recipients.

  • rTAC: 4 to 7 ng/mL day 0 to month 2; 2‐5 ng/mL month 3 to 6; 2 to 4 ng/mL month 7 to 24 (913 recipients received TAC)

  • rCSA: 100 to 150 ng/mL day 0 to month 2; 50 to 100 ng/mL month 3 to 6; 25 to 50 ng/mL month 7 to 24 (100 received CSA)


Treatment group 2 (MPA/sCNI)

  • MPS 1.44 g/d or MMF 2 g/d

  • TAC: 8 to 12 ng/mL day 0 to month 2; 6 to 10 ng/mL month 3 to 6; 5 to 8 ng/mL month 7 to 24 (916 recipients received TAC)

  • CSA: 200 to 300 ng/mL day 0 to month 2; 150 to 200 ng/mL month 3 to 6; 100 to 200 ng/mL month 7 to 24 (95 received CSA)


Co‐interventions

  • No CMV prophylaxis: weekly monitoring of CMV viral replication (pp65CMV Ag) for 6 months

  • Corticosteroids

  • Basiliximab or ATG
Outcomes

  • Number with eGFR < 50 ml/min (MDRD) or treated BPAR at 12 months

  • Composite of number with treated BPAR, graft loss, or death at 12 months

  • Death

  • Graft loss

  • Acute rejection (total and biopsy proven)

  • CMV infection, wound complications

  • Adverse effects
Notes

  • Comparison: TOR‐I versus antimetabolite
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: “A randomization sequence, stratified within treatment groups by donor type (living, deceased standard criteria, or deceased expanded criteria) and by the type of CNI (CsA or tacrolimus), was generated by a computer program and implemented by telephone‐based interactive response technology.”
Allocation concealment (selection bias) Low risk Quote: “A randomization sequence, stratified within treatment groups by donor type (living, deceased standard criteria, or deceased expanded criteria) and by the type of CNI (CsA or tacrolimus), was generated by a computer program and implemented by telephone‐based interactive response technology.”
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 outcomes (GFR, BPAR) were laboratory based and unlikely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) 
 All outcomes Low risk All included patients accounted for
Selective reporting (reporting bias) Low risk Expected outcomes reported
Other bias High risk Pharma funded by Novartis