Randomised controlled trial comparing rituximab to mycophenolate mofetil in children and young adults with steroid-dependent idiopathic nephrotic syndrome: study protocol

BMJ Open. 2021 Nov 29;11(11):e052450. doi: 10.1136/bmjopen-2021-052450.

Abstract

Introduction: Glucocorticoids induce remission in 90% of children with idiopathic nephrotic syndrome (INS). Some become steroid-dependent (SD) and require the addition of steroid sparing drugs such as calcineurin-inhibitors (CNI) or cyclophosphamide, to maintain remission. Considering the toxicity of these drugs, alternative interventions are needed for long-term treatment. The anti-CD20 antibody rituximab has shown promising steroid-sparing properties, with conflicting results in complicated forms of SD-INS. Mycophenolate mofetil (MMF) resulted effective in maintaining free-steroid remission, however, studies are limited to few uncontrolled trials with reported different dose of MMF.

Methods and analysis: This open-label, two-parallel-arm, superiority controlled randomised clinical trial will enrol children with SD-INS maintained in remission with oral glucocorticoids or CNI. Children and young adults will be randomised to either MMF (1.200 mg/m2) or rituximab (375 mg/m2) infusion. After enrolment, glucocorticoids will be tapered until complete withdrawal. We will enrol 160 children and young adults to detect as significant at the two-sided p value of 0.01 with a power >0.8 a reduction in the risk of 1-year relapse (primary end-point). As secondary endpoints, we will compare the amount of glucocorticoids required to maintain complete remission at 6 and 24 months.

Ethics and dissemination: The trial was approved by the local ethics boards (Comitato Etico Regione Liguria CER Liguria https://www.portalericerca-liguria.it/). We will publish the study results at international scientific meetings.

Trial registration numbers: NCT004585152.

Trial registration: ClinicalTrials.gov NCT04585152.

Keywords: clinical pharmacology; clinical trials; glomerulonephritis; immunology; nephrology; paediatric nephrology.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Mycophenolic Acid* / therapeutic use
  • Nephrotic Syndrome* / drug therapy
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Rituximab / adverse effects
  • Steroids
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Steroids
  • Rituximab
  • Mycophenolic Acid

Associated data

  • ClinicalTrials.gov/NCT04585152