NEFIGAN 2017.

Methods	Study design: parallel, 3‐arm RCT Time frame: December 2012 to June 2015 Duration of follow‐up: 12 months
Participants	Setting: 62 sites Country: 10; Belgium, Czech Republic, Denmark, Finland, Germany, Italy, Spain, Sweden, the Netherlands, UK Inclusion criteria: men or women aged at least 18 years with biopsy‐confirmed primary IgAN and overt proteinuria for the run‐in phase; eGFR of at least 45 mL/min/1.73 m2 and a UPCR of more than 0.5 g/g or urinary total protein of at least 0.75 g/day Number (analysed/randomised): treatment group 1 (51/51); treatment group 2 (48/51); control group (50/51) Mean age ± SD (years): treatment group 1 (40.6 ± 13.0); treatment group 2 (37.5 ± 11.9); control group (38.9 ± 12.0) Sex (M/F): treatment group 1 (37/14); treatment group 2(33/15); control group (35/15) Exclusion criteria: unacceptable BP defined as a SBP > 160 mmHg or DBP > 100 mmHg; eGFR (CKD‐EPI) loss > 30% over the entire duration of the Run‐in Phase; for women only; pregnant or breast feeding or unwilling to use adequate contraception during the trial
Interventions	Treatment group 1 TRF‐budesonide: 8 mg/day; 2 active + 2 placebo capsules daily for 9 months Treatment group 2 TRF‐budesonide: 16 mg/day; 4 active capsules daily for 9 months Control group Placebo: 4 placebo capsules daily for 9 months Co‐interventions Not reported
Outcomes	Change in UPCR at 9 months Change in UPCR, eGFR, UACR, urine albumin excretion at 12 months Presence or absence of microhaematuria Adverse events Decline in kidney function death (any cause) ESKD
Notes	The study was funded by Pharmalink AB
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomly allocated to treatment groups using a computer algorithm method of permuted blocks
Allocation concealment (selection bias)	Unclear risk	Treatment code envelopes were provided for each randomised patient. In case of emergency, the code envelope could be opened. Any unmasked patient had to be withdrawn from the trial
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind study
Blinding of outcome assessment (detection bias) All outcomes	Low 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. Reporting of adverse events may have been influenced by knowledge of treatment allocation; however participants were unaware of treatment allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	46/51 patients completed treatment and follow‐up in placebo group; 40/51 and 34/51 completed treatment and follow‐up in TRF‐budesonide 8 mg and 16 mg group, respectively. There was differential loss to follow up due to severe adverse events which were higher in the higher dose budesonide group
Selective reporting (reporting bias)	Low risk	All expected outcomes were reported
Other bias	High risk	Imbalance between groups in eGFR, weight, and time from diagnosis at baseline