Mantan 2008

Methods	Study design: parallel RCT Time frame: April 2001 to December 2003 Follow‐up period: 18 months
Participants	Setting: tertiary, single centre Country: India SRNS (proteinuria > 1g/m2/d or > 3+ on dipstick, albumin <2.5 mg/dL, oedema) despite prednisone for 4 weeks at 2 mg/kg/d; initial and late non‐responders with MCD (24), FSGS (14), MesPGN (11); aged 1 to 18 years Number IV CPA group: 26/27 evaluated Oral CPA + IV DEXA group: 23/25 evaluated Median age (range) IV CPA group: 51 (16 to 156) months Oral CPA + IV DEXA group: 92 (15 to 198) months Sex (M/F) IV CPA group: 19/8 Oral CPA + IV DEXA group: 16/9 Early/late resistance IV CPA group: 10/16 Oral CPA + IV DEXA group: 8/15 Exclusion criteria: previous immunosuppression other than prednisone; secondary SRNS; eGFR < 60 mL/min/1.73 m2
Interventions	IV CPA group IV CPA 500 mg/m2 monthly (max 1g) for 6 doses; dose increased to 750 mg/m2 monthly if no response at 3 months; dose delayed if WCC < 4000 Maintenance therapy was then started with prednisone: 0.5 mg/kg alternate days to 18 months Oral CPA + IV DEXA group Oral CPA 2 mg/kg/d from 3rd to 14th weeks and IV DEXA 5 mg/kg alternate days for 6 doses then every 2 weeks (4 pulses) and then monthly (4 pulses) Maintenance therapy was then started with prednisone: 0.5 mg/kg alternate days to 18 months Co‐interventions Alternate day prednisone (1.5 mg/kg for 1 month; 1.25 mg/kg for 1 month and 1 mg/kg for 4 months); enalapril 0.3 mg/kg/d
Outcomes	Complete (UP/C < 0.2 g/g, albumin > 2.5 g/dL) or partial remission (UP/C 0.2 to 2 g/g, albumin > 2.5 g/dL) at 6 months Treatment failure: non‐response (UP/C > 2 g/g, albumin < 2.5 g/dL) after 6 months or failure to complete treatment due to serious adverse effect or > 1 serious infection Favourable outcome at 18 months: maintenance of complete remission or steroid‐sensitive relapses Adverse events: Hypertension; neurological; severe infection; ophthalmological; steroid related; leucopenia; cystitis; hair loss; vomiting
Notes	Exclusions post randomisation but pre‐intervention: none reported Stop or end points/s: not reported Additional data requested from authors: none
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Stratified randomisation, in blocks of four, were done separately with computer‐generated numbers to allocate patients with initial and late steroid‐resistance randomly..."
Allocation concealment (selection bias)	Low risk	"Allocation was concealed in sealed opaque envelopes, which were opened by an associate not involved in the study"
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants/investigators; lack of blinding could influence management
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Primary outcome was serum albumin + urinary protein; urine protein measured either by urinalysis or UP/C. Unclear how many patients had laboratory measure of proteinuria
Incomplete outcome data (attrition bias) All outcomes	Low risk	3/52 (6%) patients excluded after randomisation (IV CPA group (1); oral CPA + IV DEXA group (2)) for non‐compliance; unlikely to have influenced results
Selective reporting (reporting bias)	Low risk	Primary outcomes: number in complete or partial remission and adverse effects reported
Other bias	Unclear risk	Funding source not reported