|Year : 2021 | Volume
| Issue : 2 | Page : 93-94
Is reduced dose of steroids not inferior to standard dose in managing relapses of children with infrequently relapsing nephrotic syndrome: A randomized controlled trial
Suprita Kalra1, Sumit Bhandari2, Puja Dudeja3, Aditi Sharma1
1 Department of Pediatrics, Army Hospital (R and R), Delhi, India
2 Department of Orthopaedics, Base Hospital, Delhi Cantt, India
3 Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India
|Date of Submission||17-Apr-2021|
|Date of Acceptance||21-Sep-2021|
|Date of Web Publication||28-Dec-2021|
Army Hospital (R and R), Delhi - 110 010
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kalra S, Bhandari S, Dudeja P, Sharma A. Is reduced dose of steroids not inferior to standard dose in managing relapses of children with infrequently relapsing nephrotic syndrome: A randomized controlled trial. Asian J Pediatr Nephrol 2021;4:93-4
|How to cite this URL:|
Kalra S, Bhandari S, Dudeja P, Sharma A. Is reduced dose of steroids not inferior to standard dose in managing relapses of children with infrequently relapsing nephrotic syndrome: A randomized controlled trial. Asian J Pediatr Nephrol [serial online] 2021 [cited 2022 Jan 17];4:93-4. Available from: https://www.ajpn-online.org/text.asp?2021/4/2/93/334031
Approximately 80% of children with idiopathic nephrotic syndrome have steroid-sensitive nephrotic syndrome, and almost half of these patients relapse frequently., Whether the dose of prednisolone used to treat relapses may influence the subsequent disease course is unclear. This open-label pilot randomized controlled trial (RCT) compared the efficacy of a reduced dose regimen, using prednisolone at 1 mg/kg alternate day (AD) for 4 weeks versus the standard regimen, prednisolone at 1.5 mg/kg AD for 4 weeks, to treat relapses, after remission had been induced with prednisolone at 2 mg/kg daily, in preventing subsequent relapses in children with infrequently relapsing nephrotic syndrome, over 12 months of follow-up. The primary objectives were to compare between groups the frequency of relapses and the proportions with frequent relapses at 1-year. The total cumulative steroid dose over 1 year was a secondary objective. The study was approved by institutional ethics committee, registered with the Indian clinical trial registry (CTRI/2018/05/013634), and conducted at a tertiary care hospital in Central India between June 2018 and August 2019. The study was not funded.
All consecutive patients, aged 1–14 years, presenting with relapse of steroid-sensitive nephrotic syndrome, were eligible if they had infrequent relapses either on no medications or while on stable doses of AD steroids, levamisole or mycophenolate mofetil (MMF). Patients with primary or secondary steroid-resistant nephrotic syndrome were excluded. Computerized random-number generator was used to generate randomization lists with variable block size. Allocation was concealed in serially numbered opaque-sealed envelopes. Following written informed consent, remission was induced with 2 mg/kg prednisolone daily and eligible patients were randomized to receive prednisolone in standard dose, i.e. 1.5 mg/kg, or reduced dose, i.e. 1 mg/kg, AD for 4 weeks. All patients were followed for 1 year, with first review at 1 month and 3-monthly thereafter, and at every relapse. Relapses during trial follow-up were treated as at randomization. Treatment failure was defined as two relapses in any 6-month period. Study stoppage rules were pre-decided and included stopping the study if, at any time during the study period, >30% of enrolled patients had treatment failure on reduced steroid dosage. Data were analyzed as per intention-to-treat analysis. Statistical analysis was done using IBM SPSS Statistics for Windows,Version 25.0. Armonk, NY: IBM Corp. In the absence of similar previous studies, this pilot RCT intended to include 30 children in each arm; formal sample size calculation was not attempted.
The baseline characteristics of the 27 patients enrolled are provided in [Supplementary Table 1]. [Figure 1] summarizes the study flow. Treatment failure was observed in nine of 15 patients randomized to reduced steroid dose group and in two of those on standard dose group. All children who had treatment failure were those who were receiving therapy with either levamisole or MMF. Key findings are as summarized in [Table 1].
Only a few recent studies have attempted to examine the efficacy of a reduced dose or duration of prednisolone therapy for treating relapses.,, The present study was terminated prematurely in accordance with a priori decided stoppage rules, when 30% of the children showed treatment failure while on reduced dose therapy. The results obtained up till that point showed that differences between number of relapses in the two groups could have achieved significance. While our results suggest that reduced steroid dosing for AD therapy in relapse, after inducing remission with prednisolone at 2 mg/kg daily, is possibly inferior to treatment with standard dosing, treatment failure was limited to patients on therapy with levamisole of MMF; no patients failed treatment among those off therapy or on AD steroids.Further, the patients randomized to reduced steroid group were younger at enrollment than those given standard therapy [Supplementary Table 1]. It is possible that the high incidence of treatment failure on reduced dose might be related to the inherently more severe disease in patients on levamisole or MMF. Large RCTs including patients with homogenous disease severity are required to examine the efficacy of reduced dose of steroids as compared to standard dose of steroids in treating relapses.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Material|| |
Treatment details of children enrolled in the study
Children not on any immunosuppression were given full dose, i.e. 2 mg/kg daily, till remission is achieved or maximum of 2 weeks and then as per randomization.
Children on long-term alternate day (AD) steroids and those on levamisole or mycophenolate mofetil (MMF) along with long-term AD steroids in addition to above for relapse, were continued on AD steroids with tapering by 5 mg every 2 weeks till 0.3 mg/kg on alternate day was reached, which was then continued for 3 months and stopped. Levamisole was given in a dose of 2–2.5 mg/kg alternate day (using 50 mg or 150 mg tablets) every alternate day in a single dose. MMF was given at a dose of 750–800 mg/m2 daily in 2 divided doses (using 250–500 mg MMF tablet or MMF suspension, 5 ml = 1 g of MMF).
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