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. 2021 Nov 15;2021(11):CD004293. doi: 10.1002/14651858.CD004293.pub4

Praga 2007.

Study characteristics
Methods

  • Study design: parallel, open‐label RCT

  • Study duration: January 2003 to September 2006

  • Duration of follow‐up: 30 months
Participants

  • Setting: multicentre

  • Country: Spain

  • Inclusion criteria: biopsy‐proven IMN with nephrotic syndrome

  • Baseline characteristics

    • Pathology stage (I/II/III/IV): treatment group (4/15/3/0); control group (4/18/1/0)

    • Mean proteinuria ± SD (g/24 hours): treatment group (7.2 ± 3.3); control group (8.4 ± 5.4)

    • Mean serum albumin ± SD (g/L): treatment group (27 ± 8); control group (29 ± 8)

    • SCr (mg/dL): treatment group (0.98 ± 0.2); control group (1.1 ± 0.3)

    • Mean GFR ± SD (mL/min/1.73 m²): treatment group (104 ± 26); control group (107 ± 63)

    • Baseline declining kidney function: no; GFR by Cockroft‐Gault formula was ≥ 50 mL/min/1.73 m² in all included patients

    • Use of ACEi or ARB during follow‐up: yes, no confounding effect. Included patients who also had to be treated with an ACEi or an ARB at their maximal tolerated doses for at least 2 months before screening. All the patients were instructed to maintain the same doses of ACEi or ARB that they were taking at randomisation until the end of the study

    • Previous immunosuppressive status: patients treated with steroids or immunosuppressive therapy within the 6‐month period before screening were excluded. There were no differences in the number of patients that had been previously treated with steroids alone or in combination with cytotoxics (previous treatment with steroids/steroids plus cytotoxics: treatment group (5/4); control group (6/4)

  • Number: treatment group (25); control group (23)

  • Mean age ± SD (years): treatment group (3.7 ± 12.1); control group (50.1 ± 12.2)

  • Sex (M/F): treatment group (20/5); control group (20/3)

  • Exclusion criteria: DM; malignancy; SLE; any other systemic disease known to be associated with secondary MGN; infections (including a positive test for hepatitis C and B virus and HIV); treated with steroids or immunosuppressive therapy within the 6‐month period before screening
Interventions Treatment group

  • TAC: 0.05 mg/kg/day, divided into two daily doses at 12‐hour intervals. Later doses were adjusted to achieve a whole blood 12‐hour trough level between 3 and 5 ng/mL. When a remission was not obtained after the first 2 months of treatment, doses were increased to achieve levels between 5 and 8 ng/mL. TAC treatment was continued for 12 months and then gradually tapered off for the next 6 months; a 25% TAC dose reduction was indicated at months 12, 14, and 16 and treatment was withdrawn by month 18. TAC doses were reduced by 25% every 2 weeks in the presence of a 50% SCr increase. If SCr persisted > 50% of baseline values 2 to 4 weeks after > 75% reduction of TAC doses, the definition of endpoint was established


Control group

  • No specific immunosuppressive treatment
Outcomes

  • Death

  • ESKD

  • 50% or 100% SCr increase

  • Partial or complete remission

  • Final proteinuria

  • Side effects leading to patient withdrawal or hospitalisation
Notes

  • Funding source: partially supported by Astellas Pharmaceuticals. Astellas did not intervene in the design or conduct of the study, analysis, and interpretation of the data or preparation of this paper

  • Baseline comparison: comparable except that DBP was significantly higher in the control group than in the TAC group at baseline
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Randomisation was performed by the clinical coordinating centre using a table of random numbers and was stratified by centres
Allocation concealment (selection bias) Low risk Allocation concealment was performed by enclosing assignments in sequentially numbered, opaque‐closed envelopes
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 A total of 8/48 (17%) randomised patients did not complete the 18‐month regimen. Two patients of the treated group (personal decision because lack of response after 6 months of treatment and a partial seizure in a patient with history of epilepsy) and one of the control group (severe oedema six months after randomisation and deafness attributed to high‐dose diuretics) withdrew from the study. Five patients (three in the control group and two in the treatment group) were lost to follow‐up between 3 and 18 months after randomisation. But they were all included in the final analyses according to the intention‐to‐treat basis
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