A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome

Kidney Int. 2018 Feb;93(2):510-518. doi: 10.1016/j.kint.2017.08.011. Epub 2017 Oct 18.

Abstract

Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated. The primary analysis cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months after the start of study medication, the time to relapse (primary endpoint) was significantly increased in the levamisole compared to the placebo group (hazard ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months of treatment, six percent of placebo patients versus 26 percent of levamisole patients were still in remission. During this period, the most frequent serious adverse event (four of 50 patients) possibly related to levamisole was asymptomatic moderate neutropenia, which was reversible spontaneously or after treatment discontinuation. Thus, in children with SSINS and frequent relapses, levamisole prolonged the time to relapse and also prevented recurrence during one year of treatment compared to prednisone alone. However, regular blood controls are necessary for safety issues.

Keywords: children; levamisole; nephrotic syndrome; randomized clinical trial; steroid sensitive.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use*
  • Age Factors
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • India
  • Italy
  • Levamisole / adverse effects
  • Levamisole / therapeutic use*
  • Male
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / drug therapy*
  • Prednisone / adverse effects
  • Prednisone / therapeutic use*
  • Recurrence
  • Remission Induction
  • Time Factors
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Glucocorticoids
  • Levamisole
  • Prednisone

Supplementary concepts

  • Nephrosis, congenital