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. 2020 Mar 12;2020(3):CD003965. doi: 10.1002/14651858.CD003965.pub3

TESTING 2017.

Methods
  • Study design: parallel, 2‐arm RCT

  • Time frame: April 2012 to November 2015

  • Duration of follow‐up: median 25 months (estimated 5 years)

Participants
  • Setting: multicentre (was to be up to 100 sites)

  • Countries: Australia, China

  • Inclusion criteria: primary IgAN proven on kidney biopsy' eGFR between 20 and 120 mL/min/1.73 m2; urinary protein excretion > 1 g/day

  • Number (analysed/randomised): treatment group (134/136); placebo group (126/126)

  • Mean age ± SD (years): treatment group (38.6 ± 11.5); placebo group (38.6 ± 10.7)

  • Sex (M/F): treatment group (86/50); placebo group (80/46)

  • Exclusion criteria: strong indication, or contraindication, for corticosteroid therapy, based on the judgement of the treating physician (patients were included if the patient and physician had clinical equipoise regarding the use of the treatment), or the use of systemic immunosuppressive therapy in the previous year

Interventions Treatment group
  • Methylprednisolone: 0.6 to 0.8 mg/kg/day; maximum, 48 mg/day, for 2 months, then tapered by 8 mg/day each month, with a total treatment period of 6 to 8 months


Control group
  • Matching placebo


Co‐interventions
  • Treatment adjusted to maximum labelled or tolerated dose of RAS blockade along with optimised BP control according to guidelines

Outcomes
  • 50% decrease in eGFR

  • ESKD

  • Death due to kidney disease

  • Composite of ESKD, 40% decrease in eGFR, and death (any cause); the composite of ESKD, 50% decrease in eGFR, and death (any cause); and each of ESKD, death due to kidney disease, and death (any cause). The secondary end points also included proteinuria reduction

  • Serious adverse events and adverse events

  • Annual decrease in GFR

Notes
  • Trial terminated because of excess serious adverse events

  • This study was supported by the National Health and Medical Research Council of Australia, the Peking University Health Central Clinical Research Project, and the Canadian Institutes of Health Research. Study drug was provided by Pfizer Pharmaceuticals

  • Trials registration identification number: NCT01560052

Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Randomisation was performed using a minimization algorithm based on the stratification variables; the algorithm was centrally generated and used by all centres to minimize any imbalances in key variables
Allocation concealment (selection bias) Low risk Randomly assigned 1:1 via a password‐protected encrypted web site interface
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 There were only 2/136 lost to follow up in methylprednisolone group. Imbalance in discontinuation between groups
Selective reporting (reporting bias) Low risk All relevant outcomes were reported
Other bias High risk Trial terminated early because of excess serious adverse events