Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Mar 1;176(3):236-243.
doi: 10.1001/jamapediatrics.2021.5189.

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

Martin T Christian  1 , Nicholas J A Webb  2 , Samir Mehta  3 , Rebecca L Woolley  3 , Nafsika Afentou  4 , Emma Frew  4 , Elizabeth A Brettell  3 , Adam R Khan  3 , David V Milford  5 , Detlef Bockenhauer  6   7 , Moin A Saleem  8   9 , Angela S Hall  10 , Ania Koziell  11   12 , Heather Maxwell  13 , Shivaram Hegde  14 , Hitesh Prajapati  15 , Rodney D Gilbert  16 , Caroline Jones  17 , Karl McKeever  18 , Wendy Cook  19 , Natalie Ives  3
Affiliations
Randomized Controlled Trial

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

Martin T Christian et al. JAMA Pediatr. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Christian reported serving as a member of the Clinical Practice Guideline Group for Steroid Sensitive Nephrotic Syndrome of the International Pediatric Nephrology Association during the conduct of the study. Dr Webb reported being an employee of Novartis since August 2018 outside the submitted work. Dr Afentou reported receiving grants from National Institute for Health Research (NIHR) outside the submitted work. Dr Frew reported receiving grants from the NIHR and Zhejiang Yongning Pharmaceutical Co Ltd outside the submitted work. Dr Brettell reported receiving grants from NIHR during the conduct of the study. Dr Milford reported receiving grants from NIHR during the conduct of the study. Dr Ives reported receiving grants from the NIHR during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT Diagram for the Modified Intention-to-Treat Population
See this image and copyright information in PMC

Comment in

References

    1. McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM. Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol. 2001;16(12):1040-1044. doi:10.1007/s004670100021 - DOI - PubMed
    1. Webb NJA, Woolley RL, Lambe T, et al. ; PREDNOS Collaborative Group . Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation. BMJ. 2019;365:l1800. doi:10.1136/bmj.l1800 - DOI - PMC - PubMed
    1. Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018;392(10141):61-74. doi:10.1016/S0140-6736(18)30536-1 - DOI - PubMed
    1. Alwadhi RK, Mathew JL, Rath B. Clinical profile of children with nephrotic syndrome not on glucorticoid therapy, but presenting with infection. J Paediatr Child Health. 2004;40(1-2):28-32. doi:10.1111/j.1440-1754.2004.00285.x - DOI - PubMed
    1. Arun S, Bhatnagar S, Menon S, Saini S, Hari P, Bagga A. Efficacy of zinc supplements in reducing relapses in steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2009;24(8):1583-1586. doi:10.1007/s00467-009-1170-5 - DOI - PubMed

Publication types