| Methods |
Study design: parallel, 2‐arm RCT Time frame: June 2004 to June 2010 Duration of follow‐up: 12 months of treatment and an average follow‐up of 88 months |
| Participants |
Setting: single centre Country: China Inclusion criteria: biopsy‐proven primary IgAN; aged 18 to 65 years; proteinuria ≥ 1.0 g/24 hours and an eGFR ≥ 30 mL/1.73 m2 Number (analysed/randomised): treatment group (40/44); control group (45/46) Mean age ± SD (years): treatment group (36.90 ± 10.49); control group (36.60 ± 11.53) Sex (M/F): treatment group (14/26); control group (22/23) Exclusion criteria: rapidly progressive IgAN (rapid decline in renal function characterized histologically by necrotising capillaritis or > 50% active crescents on biopsy); secondary IgAN due to systemic diseases such as HSP nephritis, hepatitis‐associated nephritis, lupus nephritis, etc; use of corticosteroid or other immunosuppressive agents within 6 months prior to randomisation; SCr > 250 μmol/L; severe infections; hepatitis B virus carriers and other chronic liver diseases; presence of malignancy, HIV infection, or acute central nervous system diseases; abnormal glucose metabolism; pregnancy or lactation; poor compliance or allergy to study drugs |
| Interventions |
Treatment group
Leflunomide: 40 mg/day for 3 days, after which the dose was reduced to 20 mg/day and administered for 12 months Prednisone (oral): 0.8 mg/kg/day for 4‐6 weeks. The maximum daily dose of prednisone was 40 mg. Then, prednisone was gradually tapered by 10, 5, and 2.5 mg to a maintenance dose of 5 mg/day
Control group
Co‐interventions
|
| Outcomes |
ESKD 50% increase in baseline SCr Complete remission (urine protein excretion < 0.3 g/d with stable SCr (defined as a change in SCr of ≤ 15% above baseline values) Partial remission (at least a 50% reduction in urine protein excretion compared with baseline or urine protein excretion 0.3 to 3.5 g/day with stable SCr No response was defined as urine protein excretion > 3.5 g/day or a < 50% reduction in urine protein excretion with or without kidney deterioration Relapse: reappearance of significant proteinuria, defined as > 1.0 g/d and as a urine protein excretion increase of > 50% from the lowest level of proteinuria after remission Adverse events |
| Notes |
This study was supported by the National Natural Science Foundation of China (81370794 and 81570604) as well as by a program from the Shanghai Health Bureau (No. ZHYY‐ZXYJHZX‐1‐02) Trials registration identification number: not reported |
| 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 |
Insufficient information to permit judgement |
| 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. However, reporting of adverse events may have been influenced by knowledge of treatment allocation |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
37/44 participants assigned to leflunomide completed the study follow‐up. 43/46 patients assigned to steroid therapy completed study follow‐up |
| Selective reporting (reporting bias) |
High risk |
All relevant outcomes, except death (any cause), were reported |
| Other bias |
Low risk |
The study appeared to be free of other sources of bias |
