STOP‐IgAN 2008.

Methods	Study design: 2‐group, parallel, group‐sequential RCT Time frame: February 2008 to February 2015 Duration of follow‐up: 36 months
Participants	Setting: multicentre (32 sites) Country: Germany Inclusion criteria: primary IgAN confirmed on biopsy; 18 to 70 years; proteinuria level > 0.75 g/day of urinary protein excretion plus arterial hypertension (defined by the use of antihypertensive medication or by an ambulatory BP ≥ 140/90 mmHg), impaired kidney function (defined as an eGFR < 90 mL/min/1.73 m2), or both Number (analysed/randomised): treatment group (80/80); control group (82/82) Mean age ± SD (years): treatment group (45.8 ± 12.5); control group (42.8 ± 13.1) Sex (M/F): treatment group (61/19); control group (56/24) Exclusion criteria: eGFR < 30 mLmin/1.73 m2; secondary and rapidly progressive, crescentics IgAN; other CKDs; any prior immunosuppressive therapy
Interventions	Treatment group Patients with GFR of at least 60 mL/min/1.73 m2 Methylprednisolone (IV): 1 g/ day for 3 days at the start of months 1, 3, and 5; and oral prednisolone at a dose of 0.5 mg/kg per 48 hours on the other day Patients with an eGFR between 30 and 59 mL/min/1.73 m2 CPA: 1.5 mg/kg/day for 3 months, followed by AZA at a dose of 1.5 mg/kg/day during months 4 through 36 Prednisolone (oral): 40 mg/day, tapered to 10 mg/day, over the first 3 months of the study, 10 mg/day during months 4 through 6, and 7.5 mg/day during months 7 through 36 months Control group No treatment Co‐interventions Comprehensive supportive care that included blockers of the RAS to lower BP to a target below 125/75 mm Hg. If proteinuria remained above the target of 0.75 g/day of urinary protein excretion despite blood‐pressure control, the dose of RAS blocker was increased to the maximum approved daily dose or to the highest dose at which the patient did not have unacceptable side effects. Patients received dietary counselling and were advised to quit smoking and to avoid nonsteroidal antiinflammatory drugs and other nephrotoxins. Total cholesterol levels were lowered to < 200 mg/dL (5.2 mmol/L) with the use of statins, if necessary
Outcomes	Complete remission: defined as proteinuria with a UPCR of < 0.2 and stable kidney function with a decrease in GFR of < 5 mL/min/1.73 m2 from the baseline eGFR at the end of the 3‐year trial phase GFR loss of 15 mL/min or higher from baseline GFR GFR loss ≥ 30 mL/min from baseline Annual change in slope of the reciprocal of SCr Proteinuria Disappearance of microhaematuria ESKD death (any cause) Adverse events including malignancy/infection
Notes	The study was funded through German Federal Ministry of Education and Research grant GFVT01044604
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	Randomisation codes that were used to assign patients in a 1:1 ratio were generated by means of covariate adaptive randomisation with respect to factors that had the potential to modify the treatment effect (i.e., eGFR and proteinuria). Telephone randomisation by the study secretary. After the investigator establishes the eligibility of the patient to participant in the study, the study centre sends a fax to the Trial Office. The Trial Office assigned a treatment to the patient after being sent the following information: initials, gender, age, CrCl, degree of proteinuria
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label 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. Reporting of adverse events may have been influenced by knowledge of treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	4/82 assigned to immunosuppression were lost to follow up. 4/80 assigned to supportive care were lost to follow up
Selective reporting (reporting bias)	Low risk	All relevant outcomes were reported
Other bias	Low risk	The study appeared to be free of other sources of bias