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The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

Wong MG 1 , Lv J 2 , Hladunewich MA 3 , Jha V 4 , Hooi LS 5 , Monaghan H 1 Show all authors , Zhao M 2 , Barbour S 6 , Reich HN 7 , Cattran D 7 , Glassock R 8 , Levin A 6 , Jardine MJ 9 , Wheeler DC 10 , Woodward M 1 , Billot L 1 , Chan TM 11 , Liu ZH 12 , Johnson DW 13 , Cass A 1 , Feehally J 14 , Floege J 15 , Remuzzi G 16 , Wu Y 17 , Agarwal R 18 , Zhang H 2 , Perkovic V 1 , TESTING Study Group

Affiliations 

  • 1 The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  • 2 Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
  • 3 Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
  • 4 The George Institute for Global Health India, New Delhi, India
  • 5 Department of Medicine, Sultanah Aminah Hospital, Johor Bahru, Malaysia
  • 6 Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
  • 7 Division of Nephrology, University Health Network, Toronto, Ontario, Canada
  • 8 Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA
  • 9 The NHMRC Clinical Trial Centres, University of Sydney, Camperdown, New South Wales, Australia
  • 10 Department of Renal Medicine, University College London, London, United Kingdom
  • 11 Department of Medicine, University of Hong Kong, Hong Kong, China
  • 12 National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • 13 Australasian Kidney Trials Network, University of Queensland, Brisbane, Queensland, Australia
  • 14 Department of Renal Medicine, University of Leicester, Leicester, United Kingdom
  • 15 Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany
  • 16 Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
  • 17 Department of Epidemiology and Biostatistics, Peking University Clinical Research Institute, Beijing, China
  • 18 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Am J Nephrol, 2021;52(10-11):827-836.
PMID: 34731857 DOI: 10.1159/000519812

Abstract

INTRODUCTION: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants.

METHODS: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment.

RESULTS: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen.

CONCLUSIONS: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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