Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome: The PREDNOS 2 Randomized Clinical Trial

Autor: Martin T. Christian, Nicholas J. A. Webb, Samir Mehta, Rebecca L. Woolley, Nafsika Afentou, Emma Frew, Elizabeth A. Brettell, Adam R. Khan, David V. Milford, Detlef Bockenhauer, Moin A. Saleem, Angela S. Hall, Ania Koziell, Heather Maxwell, Shivaram Hegde, Hitesh Prajapati, Rodney D. Gilbert, Caroline Jones, Karl McKeever, Wendy Cook, Natalie Ives
Rok vydání: 2021
Předmět:
Zdroj: Christian, M T, Webb, N J A, Mehta, S, Woolley, R L, Afentou, N, Frew, E, Brettell, E A, Khan, A R, Milford, D V, Bockenhauer, D, Saleem, M A, Hall, A S, Koziell, A, Maxwell, H, Hegde, S, Prajapati, H, Gilbert, R D, Jones, C, McKeever, K, Cook, W & Ives, N 2021, ' Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome : The PREDNOS 2 Randomized Clinical Trial ', JAMA Pediatrics . https://doi.org/10.1001/jamapediatrics.2021.5189
JAMA Pediatrics
ISSN: 2168-6211
Popis: Key Points Question In children with relapsing corticosteroid-sensitive nephrotic syndrome, does daily low-dose corticosteroid given at the time of upper respiratory tract infection prevent upper respiratory tract infection–related relapse? Findings In this randomized clinical trial of 365 children, daily low-dose corticosteroid therapy resulted in no difference in the frequency of upper respiratory tract infection–related relapses compared with placebo. Meaning Results of this study suggest that low-dose corticosteroid treatment is not beneficial as a strategy to prevent upper respiratory tract infection–related relapses.
Importance In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. Objective To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection–related relapses. Design, Setting, and Participants This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. Interventions At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. Main Outcomes and Measures The primary outcome was the incidence of first upper respiratory tract infection–related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. Results The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection–related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, −0.02; 95% CI, −0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). Conclusions and Relevance The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. Trial Registration isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39
This randomized clinical trial investigates whether a low daily dose of prednisolone in children with relapsing steroid-sensitive nephrotic syndrome prevents upper respiratory tract infection–related relapse.
Databáze: OpenAIRE
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