A randomised controlled trial of two corticosteroid dosages for relapsed childhood steroid-sensitive nephrotic syndrome: the OPtimising dosE in Nephrotic syndrome (OPEN) trial protocol

Background Steroid sensitive nephrotic syndrome (SSNS) is a relapsing-remitting condition treated with repeated courses of high-intensity corticosteroids. Corticosteroid-related adverse effects cause morbidity and reduce quality of life. Methods The OPtimising dosE in Nephrotic syndrome (OPEN) trial is a multi-centre, randomised, controlled, non-inferiority trial comparing high-intensity with low-intensity corticosteroid treatment in children (aged 1-16 years) with relapsed SSNS. For induction, participants will receive prednisolone 60mg/m 2 (maximum 60mg) or 30 mg/m 2 (maximum 30mg) daily until remission. A second randomisation, conditional upon remission, allocates maintenance prednisolone 40mg/m 2 (maximum 40mg) or 20mg/m 2 (maximum 20mg) every other day for 4 weeks. All Australian and New Zealand tertiary paediatric nephrology centres will participate. Exclusion criteria include corticosteroid use within 14 days, familial nephrotic syndrome, or biopsy findings other than minimal change disease or focal segmental glomerulosclerosis; non-corticosteroid immunosuppression is permitted. The sample size is 330, assuming median times to remission and relapse of 9 and 100 days. The primary outcomes are time-to-remission (induction) and time-to-relapse (maintenance), analysed as the difference in restricted mean survival time (28- and 270-day horizons) with non-inferiority margins of 3 and 30 days, and power calculated assuming a true difference of zero. Randomisation (1:1) will use site-stratified, variably sized permuted blocks generated by the central trial pharmacy; participants, clinicians, site pharmacies, investigators, and data analysts will be blinded. Discussion OPEN will define the safety and efficacy of low-intensity corticosteroid treatment in relapsed SSNS; if non-inferiority is demonstrated, cumulative corticosteroid exposure could be halved. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12624001201561p. Prospectively registered on 1 October 2024.