Shima 2018.

Methods	Study design: parallel, 2‐arm RCT Time frame: August 2001 to March 2009 Duration of follow‐up: 24 months
Participants	Setting: multicentre (number of sites not reported) Country: Japan Inclusion criteria: children with new diagnosed severe IgAN with diffuse mesangial proliferation by renal biopsy; 2 to 18 years; sufficient renal biopsy specimens available for pathological evaluation (minimum of 10 glomeruli); heavy proteinuria > 0.3 g/dL and hypoproteinaemia (serum total protein ≤ 6.0 g/dL) on at least one occasion between onset and entry to the study due the Japanese health insurance system regulation the use of mizoribine Number (analysed/randomised): treatment group (34/35); control group (36/36) Median age, IQR (years): treatment group (11.7, 9.6 to 13.3); control group (10.7, 7.4 to 12.8) Sex (M/F): treatment group (10/24); control group (24/12) Exclusion criteria: secondary IgAN such as IgA vasculitis, systemic lupus erythematosus, accompanied by liver disease; previous treatment with corticosteroids or immunosuppressive drugs
Interventions	Treatment group Prednisolone: 2 mg/kg/day in 3 divided doses for a total dose of not more than 80 mg/day for 4 weeks. This was followed by 2 mg/kg every 2 days, given as a single dose in the morning every other day for 4 weeks, 1.5 mg/kg per 2 days for 4 weeks, and 1 mg/kg day per 2 days for 21 months Mizoribine: 4 mg/kg/day in two divided doses for a total dose of no more than 150 mg/day for 24 months Warfarin: single morning dose to maintain thrombotest at 20% to 50% for 24 months Dipyridamole (oral): 6 mg/kg/day in 3ree divided doses for a total dose of up to 300 mg/day for 24 months Control group Prednisolone: 2 mg/kg/day in 3 divided doses for a total dose of not more than 80 mg/day for 4 weeks. This was followed by 2 mg/kg every 2 days, given as a single dose in the morning every other day for 4 weeks, 1.5 mg/kg per 2 days for 4 weeks, and 1 mg/kg day per 2 days for 21 months Mizoribine: 4 mg/kg/day in 2 divided doses for a total dose of no more than 150 mg/day for 24 months Co‐interventions Not reported
Outcomes	Efficacy Blood counts (including haemoglobin, white blood cells, and platelets) Adverse events Remission of proteinuria Thrombotest SCr BUN Serum IgA concentration Urinary protein excretions Hemostix test BP Body weight
Notes	Funding: Health and Labor Sciences Research Grant from the Japanese Ministry of Health Labor and Welfare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	Sealed envelopes. Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Non‐double‐blind study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinding of outcome assessment not specifically reported. Key outcomes were objective laboratory measures and were unlikely to be affected by any knowledge of treatment allocation. However, reporting of adverse events may have been influenced by knowledge of treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 patient in the treatment group withdrew consent after allocation. all other patients completed the study
Selective reporting (reporting bias)	High risk	Data for outcomes such as ESKD, death (any cause), malignancy, and infections were not reported
Other bias	Low risk	The study appeared to be free of other sources of bias