| Study characteristics |
| Methods |
Study design: parallel, open‐label RCT Study duration: 1976 to 1985 Duration of follow‐up: median 5 years (2 to 11) in the first report and 10 years in the second report |
| Participants |
setting: multicentre country: Italy Inclusion criteria: biopsy‐proven IMN with nephrotic syndrome -
Baseline characteristics
Pathology stage (I/II/III/IV): treatment group (11/21/8/2); control group (7/23/7/2) Mean proteinuria ± SD (g/24 hours): treatment group (6.18 ± 2.98); control group (5.30 ± 2.84) Hypertension: treatment group (8/42); control group (12/39) Mean SCr ± SD (μmol/L): treatment group (93.8 ± 21.5); control group (93.1 ± 25.3) Baseline declining kidney function: no Use of ACEi or ARB during follow‐up: yes; 2 (1 per group) were recorded to receive captopril during the 5‐year follow‐up Previous immunosuppressive status: patients who had previously received steroids or cytotoxic therapy were excluded
Number: treatment group (42); control group (39) Mean age, range (years): treatment group (43.5, 15 to 70); control group (42, 16 to 74) Sex (M/F): treatment group (34/8); control group (29/10) Exclusion criteria: < 16 years; SCr > 150 µmol/L; previous steroid or cytotoxic therapy; clinical or biological evidence of SLE, DM, drug reaction, viral hepatitis, or other infection |
| Interventions |
Treatment group
-
Chlorambucil + steroids
Methylprednisolone (IV): 1g was given for 20 to 30 minutes on 3 consecutive days Cycle A: on day 4, oral methylprednisolone (0.4 mg/kg/day) or prednisone (0.5 mg/kg/day) was given in a single morning dose for 27 days. At the end of the first month, the steroid was discontinued Cycle B: chlorambucil (0.2 mg/kg/day) for 1 month; the dose was lowered if the leukocyte count fell below 5.0x109/L. After 1 month the chlorambucil was discontinued Cycle A Cycle B Cycle A Cycle B
The entire duration of the treatment period was 6 months. During the study, it was decided that clinicians would be free to treat the patients again, but not until 2 years after the first 6‐month course of therapy. No patient relapsed within the first 2 years
Control group
Co‐interventions
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| Outcomes |
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| Notes |
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| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
For all patients, the indications for therapy were contained in sealed, completely opaque envelopes numbered in sequence according to a table of random numbers |
| Allocation concealment (selection bias) |
Low risk |
Randomisation method described could not allow investigators/participants to know or influence intervention group before eligible participant entered in the study |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
Open‐label study |
| Blinding of outcome assessment (detection bias)
All outcomes |
Unclear risk |
Insufficient information to permit judgement |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Four patients in the treatment group did not complete the 6‐month therapy, these patients were continued to be followed up because of side effects. They were considered to be treated patients in the data analysis, according to the intention‐to‐treat principle. In the case of patients who died, data obtained before the time of death were included. 3/81 patients (3%) were lost to 5‐year follow‐up: two controls and one treated patient were lost to follow‐up 22, 28, and 24 months after randomisation, respectively. At the second analysis, 9/42 (21%) treated patients and 10/39 (26%) controls were lost to follow‐up from 12 to 96 months after randomisation. These 3 patients were also considered in the analyses |
| Selective reporting (reporting bias) |
Low risk |
The study protocol was not available but it was clear that the published reports included all expected outcomes, including those that were pre‐specified |
| Other bias |
Low risk |
The study appeared to be free of other sources of bias |
